Lupus erythematosus is an autoimmune disorder striking every organ system. Its many presentations can mimic many diseases. This disease requires close cooperation between the treating physician and the pathologist. The systemic disease, known as Systemic Lupus Erythematosus (SLE) can be diagnosed with 4 or more of the 11 criteria below, either serially or simultaneously, during any interval of observation. In general, arthritis and joint complaints comprise the majority of initial signs and symptoms but ultimately 80% of patients will present with skin manifestations.
Patients may be treated with corticosteroids and immunosuppressive agents. However, these patients are immunocompromised and infections are common. Death is usually secondary to infectious complications, renal failure, or central nervous system disease.
The story of lupus does not end here. There are several well-established variants, such as Discoid Lupus Erythematosus (DLE), that involve selected organ systems and present with different ANA patterns. The outline below describes some of these important clinical variants.
Disease Associations Crohn's disease
Other Diagnostic Testing
Anti-phospholipid antibody and Lupus anticoagulant
Lupus band test
Gross Appearance and Clinical Variants 1997 Revised Criteria
Histopathological Features and Variants
Anti-Ro associated LE
Lupus erythematous profundus
Papular and Nodular Mucinosis
Parvovirus B19 induced LE
Subacute cutaneous LE
Differential Diagnosis Lymphoma
SLE vs SCLE
Prognosis and Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGIC ASSOCIATIONS CHARACTERIZATION SYNONYMS SLE, DLE, SCLE INCIDENCE 1 in 2500 persons
5.8/100,000 in whites
24.1/100,000 in Asians
1/1000 in Blacks
AGE RANGE-MEDIAN SLE Third and fourth decades SCLE Infants and elderly DLE Onset usually 4th decade
5% present <15 years or 8th decade
SEX (M:F) SLE More common in women with a 9:1 female-to-male ratio and a frequency of 1 in 700 in women of childbearing age SCLE DLE Women 2-3:1 GEOGRAPHY Blacks and Asians have increased prevalence of SLE GENETIC Increased risk among family members 20% of clinically unaffected first degree relatives have ANA Higher rate of concordance among monozygotic twins than dizygotic twins 24% vs 3% Linkage of polymorphisms of HLA-DQ Leads to production of anti-double stranded DNA, anti-Sm, and antiphospholipid antibodies NON-GENETIC Ultraviolet light exposure Induces keratinocytes to produce IL-1 Sex hormones Ten times greater frequency among women of reproductive age
Arthritis Rheum 1990;33:1665
One explanation for the increased incidence of the disease in women may relate to the fact women are hypomethylators of DNA
Hypomethylation of DNA correlates with increased biologic activity of lymphocytes and is the postulated mechanism of induction of drug-induced LE with certain classical agents such as hydralazine
DISEASE ASSOCIATIONS CHARACTERIZATION CROHN'S DISEASE
Fatal evolution of systemic lupus erythematosus associated with Crohn's disease.
Chebli JM, Gaburri PD, de Souza AF, Dias KV, Cimino KO, de Carvalho-Filho RJ, Lucca FA.
Division of Gastroenterology, Department of Medicine, Juiz de Fora University, School of Medicine, Juiz de Fora, MG, Brazil.
Arq Gastroenterol 2000 Oct-Dec;37(4):224-6 Abstract quote
The authors describe the case of a young Brazilian woman who was treated of ileocolonic Crohn's disease sparing rectum, as confirmed by colonoscopy and histopathological examination.
After a 4-year course of sulfasalazine treatment, she presented with skin facial lesions in vespertilio, fever, arthralgias and high titers of anti-ANA and LE cells. A sulfasalazine-induced lupus syndrome was diagnosed, because after sulfasalazine withdrawal and a short course of prednisone, the clinical symptoms disappeared and the laboratory tests returned to normal. Mesalazine 3 g/day was started and the patient remained well for the next 3 years, when she was again admitted with fever, weakness, arthralgias, diplopy, strabismus and hypoaesthesia in both hands and feet, microhematuria, haematic casts, hypocomplementemia and high titers of autoimmune antibodies.
A diagnosis of associated systemic lupus erythematosus was made. Although a pulsotherapy with methylprednisolone was started, no improvement was noticed. A cyclophosphamide trial was tried and again no positive results occurred. The patient evolved to severe clinical manifestations of general vasculitis affecting the central and peripheral nervous system and lungs, having a fatal evolution after 2 weeks.
Although uncommon, the association of both disease may occur, and the authors call attention to this possibility, making a brief review of literature.
Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure.
James JA, Neas BR, Moser KL, Hall T, Bruner GR, Sestak AL, Harley JB.
University of Oklahoma Health Sciences Center, Oklahoma City, USA.
Arthritis Rheum 2001 May;44(5):1122-6 Abstract quote
OBJECTIVE: The possible molecular mimicry of the Epstein-Barr virus (EBV) peptide PPPGRRP by the peptide PPPGMRPP from Sm B'/B of the human spliceosome is consistent with the possibility that EBV infection is related to the origin of systemic lupus erythematosus (SLE) in some patients. Association of EBV exposure with SLE was therefore tested for and subsequently found in children and adolescents (odds ratio [OR] 49.9, 95% confidence interval [95% CI] 9.3-1,025, P < 10(-11)). These results were confirmed at the level of EBV DNA (OR > 10, 95% CI 2.53-infinity, P < 0.002). Much smaller seroconversion rate differences were found against 4 other herpes viruses. Herein, we extend these studies to adults and test the hypothesis that EBV infection is associated with adult SLE.
METHODS: We selected 196 antinuclear antibody-positive adult SLE patients (age > or =20 years) and 2 age-, race-, and sex-matched controls per patient. SLE patients and matched controls were tested for evidence of previous infection with EBV, cytomegalovirus (CMV), herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), or varicella-zoster virus (VZV) by standardized enzyme-linked immunosorbent assays.
RESULTS: Of the 196 lupus patients tested, all but 1 had been exposed to EBV, while 22 of the 392 controls did not have antibodies consistent with previous EBV exposure (OR 9.35, 95% CI 1.45-infinity, P = 0.014). No differences were observed between SLE patients and controls in the seroconversion rate against CMV, HSV-2, or VZV.
CONCLUSION: These new data from adults, along with the many suggestive features of EBV infection, are consistent with the contribution of this infection to the etiology of SLE.
Guillain-Barre syndrome in a child with systemic lupus erythematosus and anti-Ro/SSA and anti-La/SSB autoantibodies.
Miyagawa S, Nakajima M, Nishio K, Sogami J, Tsubakimoto A, Yoshioka A, Shirai T.
Departments of Dermatology, Paediatrics and Emergency Medicine, Nara Medical University, Kashihara City, Nara 634, Japan.
Br J Dermatol 2000 Nov;143(5):1050-4 Abstract quote
We report a 9-year follow-up of a girl with systemic lupus erythematosus (SLE) and probable Sjogren's syndrome.
At the age of 7 years, the patient developed a chilblain-like eruption with features of SLE, including leucopenia, oral ulcers, positive rheumatoid and antinuclear antibodies and positive anti-dsDNA, anti-Ro/SSA and anti-La/SSB antibodies.
At the age of 13 years she developed Guillain-Barre syndrome, which completely resolved with aggressive treatment, including high-dose corticosteroids and the use of plasma exchange followed by intravenous gammaglobulin.
M ID-DERMAL ELASTOLYSIS
Middermal Elastolysis in Two Patients With Lupus Erythematosus
Alan S. Boyd, etal.
Am J Dermatopathol 2001;23:136-138
Despite lupus erythematosus (LE) being considered a ``connective tissue disease,'' little has been written about the elastic fiber changes in the skin of affected patients.
We report our histologic findings in two patients with unusual cutaneous lesions. Elastic fiber loss was noted, and scattered giant cells with elastic fiber phagocytosis were prominent in one patient. The findings are similar to those described for middermal elastolysis. Other authors have reported patients with LE and elastic fiber loss resembling anetoderma.
We believe that a spectrum of elastic fiber changes can occur in patients with LE and may be induced by infiltrating lymphocytes and/or circulating antibodies.
Coexistence of lupus erythematosus and porphyria cutanea tarda in fifteen patients.
Gibson GE, McEvoy MT.
Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.
ients with coexistent disease.
J Am Acad Dermatol 1998 Apr;38(4):569-73 Abstract quote
BACKGROUND: Lupus erythematosus (LE) and porphyria cutanea tarda (PCT) may have similar clinical presentations, and their coexistence presents special problems in diagnosis and management.
OBJECTIVE: The purposes of this study were to describe a patient with discoid LE and PCT and to present a review of 15 patients with coexistent LE (all variants) and PCT.
METHODS: The medical records of all patients with coexistent LE and PCT seen between 1976 and 1995 were retrospectively reviewed.
RESULTS: Of 6179 cases of LE and 676 cases of porphyria (all variants), there were 15 patients, 6 men and 9 women, with coexistent LE and PCT. The mean age at diagnosis of LE was 42.8 years and of PCT was 48 years. Nine patients had discoid LE; five patients had systemic LE, and one patient had subacute cutaneous LE. The initial diagnosis was LE in eight patients, PCT in five patients, and simultaneous LE and PCT in two patients. Precipitating factors for PCT included alcohol in seven patients, iron overload in one patient, and estrogen in one patient. Treatment of LE with hydroxychloroquine 200 mg daily precipitated PCT in two patients. Patients were treated with phlebotomy or low-dose antimalarials for PCT. Patients with systemic LE received systemic glucocorticoid therapy. Patients with discoid LE and subacute cutaneous LE were treated with topical glucocorticoids.
CONCLUSION: The association of LE and PCT poses therapeutic challenges. The preferred treatment for one may exacerbate the other. Use of standard dose antimalarials for LE is inadvisable, and phlebotomy or low-dose antimalarials should be used cautiously in patients with coexistent disease.
TOXIC EPIDERMAL NECROLYSIS
Lupus-associated toxic epidermal necrolysis: A novel manifestation of lupus?
Mandelcorn R, Shear NH.
Division of Dermatology, Department of Medicine, University of Toronto.
J Am Acad Dermatol 2003 Apr;48(4):525-9 Abstract quote
BACKGROUND: Toxic epidermal necrolysis is an acute mucocutaneous reaction characterized by extensive cutaneous and mucosal sloughing and systemic involvement. It is generally associated with drug ingestion.
Objective and Methods: We describe 2 patients who developed typical clinical and histopathologic features of toxic epidermal necrolysis with unusual subacute progression, absence of systemic involvement or high-risk drug ingestion, and features of lupus erythematosus.
CONCLUSION: We propose that this constellation of features represents a new entity not previously described. This entity may represent a more severe variant of Rowell's syndrome or, alternatively, a novel manifestation of lupus erythematosus
PATHOGENESIS CHARACTERIZATION SLE GENERAL
J Cutan Pathol. 2005 Sep;32(8):537-40. Abstract quote
Background: The link between the lupus band and pathogenesis remains controversial, because immunoglobulins and complement components, including the membrane attack complex, can be found in both lesional and non-lesional skin of patients with systemic lupus erythematosus (SLE). The expression of proteins that regulate complement has not been previously investigated in the skin of patients with SLE.
Aim: The aim of this study is to compare the expression of protectin (CD59), which demonstrates the activation of the classical pathway of complement, in non-lesional skin obtained from patients with SLE with its expression in normal skin. This may help us explain the link between the lupus band and pathogenesis of cutaneous lupus erythematosus.
Methods: An indirect immunofluorescence technique was performed in order to provide unequivocal evidence for the activation of complement via the classical pathway and to compare the expression of CD59 in non-lesional skin from patients with SLE with normal skin samples obtained from healthy people. Results: The activation of the classical pathway of complement was demonstrated in non-lesional skin in more than 90% of SLE patients investigated in this study. Staining intensity of the complement regulatory protein CD59 was markedly increased in the majority of non-lesional skin samples obtained from patients with SLE, compared to that from normals.
Conclusions: CD59 is overexpressed in non-lesional skin in which complement activation has occurred. It seems likely that an increased and continuous CD59 expression may be important for maintaining the integrity of the skin BMZ during inflammatory responses involving complement activation in SLE skin.
Molecular aspects in the pathogenesis of human systemic lupus erythematosus.
Liossis SN, Tsoko GC.
Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
Arch Immunol Ther Exp (Warsz) 2000;48(1):11-9 Abstract quote
Systemic lupus erythematosus is a common and often devastating systemic autoimmune disease of unknown etiology.
In this communication we review the latest developments of the molecular pathogenesis of human lupus. Novel genetic studies of multiplex lupus families have revealed potential disease-associated genome intervals, put special emphasis on genetic loci mapping in the long arm of chromosome 1 and have underscored the complexity of the underlying genetic background. New data have emerged on the role of estrogens in the function of lymphocytes and a number of studies have recently emphasized the relative Th-1/Th-2 cytokine imbalance in favor of a Th-2 type cytokine immune response.
Finally, novel experiments have revealed an abnormal antigen receptor-mediated signaling process in lupus T and B cells, which may influence the aberrant expression and function of costimulatory molecules as well as of other aspects of immune cell function.
It is important to decipher the underlying molecular mechanisms that govern the expression of human lupus, because we may design novel, rational approaches in the treatment of a human lupus, a disease that has high morbidity and mortality.
Oligoclonal B-cell response to self antigens CD4 T cells drive the B cells to produce autoAb Type III hypersensitivity Mediates most of the visceral changes through immune complexes and subsequent activation of complement DNASE 1 Genetic failure to produce
DNase is an enzyme which breaks down damaged DNA
In laboratory mice bred with a genetic inability to encode the enzyme, 75% developed lupus symptoms within 6-8 months, although all were normal at birth
Lends support to hypothesis that impairment of normal physiological processes of cellular debris disposal predisposes to SLE
Mutation of DNASE1 in people with systemic lupus erythematosus.
Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y.
Department of Pediatrics, School of Medicine, University of Tokushima, Tokushima 770-8503, Japan.
Nat Genet 2001 Aug;28(4):313-4 Abstract quote
Systemic lupus erythematosus (SLE) is a highly prevalent human autoimmune diseases that causes progressive glomerulonephritis, arthritis and an erythematoid rash. Mice deficient in deoxyribonuclease I (Dnase1) develop an SLE-like syndrome.
Here we describe two patients with a heterozygous nonsense mutation in exon 2 of DNASE1, decreased DNASE1 activity and an extremely high immunoglobulin G titer against nucleosomal antigens.
These data are consistent with the hypothesis that a direct connection exists between low activity of DNASE1 and progression of human SLE.
HLA-B8 Br J Dermatol 1977;96:139
Absent in DLE patients
Patients who present with discoid lesions and evolve quickly into a clinical picture of SLE, are frequently HLA-B8 positive
Arch Dermatol 2000;136:1497-1501
Associated with type 1 cytokines characterized by expression of IL-2 and IFN-gamma
Suggests dysregulated T-cell cytokine production
Hum Pathol 1997;28:67
Clin Exp Immunol 1989;78:454
Am J Dermatopathol 1999;21:129
Under some conditions, UV light, viral infection, alteration of the calcium milieu, and estrogen exposure-Ro/SSA particles may be displaced from the nucleus to the cell surface
May explain the enhanced photosensitivity of skin and worsening symptomatology with calcium channel blockers and viral illness
Ro/SSA antigen is a 60 kDa protein attached to small RNAs to produce a 100 kDa complex with nuclear localization in normal adult skin
If insult such as UV, viral infection, or altered cytosolic calcium milieu occurs, Ro/SSA particles manifest upregulated or displaced expression from the nucleus to the cytosol and from the cytosol to the cell surface
This may explain the photosensitivity or photoreproduceability of skin lesions in anti-Ro/SSA positive LE patients and the worsening of disease symptoms in connective tissue disease patients experiencing viral illness
Rheum Dis Clin North Am 1994;20:61
J Clin Invest 1991;88:680
Drug induced pertubation of lymphocyte function might generate an immunologic milieu permissive to development of autoantibodies against ribonucleoproteins
Depression in T-suppressor lymphocyte activity attributed to deficient function of 2H4+ T cell subset, inducers of T-suppressor cell activity
Drugs may abrogate T-suppressor cell activity:
1) Enhanced bcl-2 expression leading to apoptosis of lymphocytes, expanding the lymphocyte pool
2) Lowered cytosolic calcium concentration
Predictors of clinical outcome and radiologic progression in patients with neuropsychiatric manifestations of systemic lupus erythematosus.
Karassa FB, Ioannidis JP, Boki KA, Touloumi G, Argyropoulou MI, Strigaris KA, Moutsopoulos HM.
Department of Pathophysiology, School of Medicine, University of Athens, Athens, Greece.
Am J Med 2000 Dec 1;109(8):628-34 Abstract quote
PURPOSE: We sought to identify the predictors of clinical outcome and of the evolution of cerebral abnormalities in patients with neuropsychiatric systemic lupus erythematosus (SLE).
SUBJECTS AND METHODS: Thirty-two patients with SLE (including 14 with the antiphospholipid syndrome) who had been hospitalized with primary neuropsychiatric disease were observed prospectively for at least 2 years. Laboratory and clinical characteristics and data from magnetic resonance imaging (MRI) studies obtained during the hospitalization and 2 years later were evaluated. We ascertained nonreversible or new MRI changes and clinical outcomes, including neuropsychiatric events, during follow-up.
RESULTS: Cranial MRI scans on admission were abnormal in 26 (81%) of the 32 patients. Patients with the antiphospholipid syndrome were more likely to have focal cerebral white matter lesions (odds ratio [OR] = 12, 95% confidence interval [CI]: 2.0 to 72). After 2 years, neuropsychiatric deficits substantially improved in 22 (69%) of the patients, stabilized in 6 (19%), and deteriorated in 4 (12%). The number of prior neuropsychiatric events was associated with persistent MRI lesions (OR = 4.8 per each event, 95% CI: 1.1 to 21) and unfavorable clinical outcome (OR = 4.3 per each event, 95% CI: 1.4 to 13) at 2 years. The antiphospholipid syndrome also predicted an unfavorable clinical outcome at 2 years (OR = 11, 95% CI: 1.7 to 65).
CONCLUSIONS: Among patients with SLE who have neuropsychiatric disease, prior neuropsychiatric events and the antiphospholipid syndrome increase the risk of adverse outcomes.
LABORATORY MARKERS ANCA Antinuclear antibodies
Anti-nuclear antibodies (ANA) are usually present-immunofluorescence test for ANA is positive in nearly all cases
Of these ANAs, antibodies directed against double stranded DNA and the Smith antigen (Sm) are diagnostic for the systemic lupus erythematosus
The lupus anticoagulant may also be present
Antineutrophil cytoplasmic antibodies in childhood systemic lupus erythematosus.
Bakkaloglu A, Topaloglu R, Saatci U, Ozdemir S, Ozen S, Bassoy Y, Besbas N.
Department of Pediatric Nephrology and Rheumatology, Hacettepe University, School of Medicine, Ankara, Turkey.
Clin Rheumatol 1998;17(3):265-7 Abstract quote
. We aimed to evaluate the presence of peripheral antineutrophil cytoplasmic antibodies (p-ANCA) and cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) in children with SLE and to correlate its association of laboratory findings.
Twenty-one children with SLE were studied. Serum samples in patients were tested by indirect immunofluorescence (IIF) slide kit (INOVA) for c-ANCA and p-ANCA and by ELISA for myeloperoxidase (MPO-ANCA) and proteinase 3 (PR3-ANCA). All the patients but two were quiescent for lupus at the time of sampling. Sixteen of 21 patients showed positive IIF staining whereas only 5 had MPO-ANCA and 2 of nine PR3-ANCA.
The data suggests that SLE may be associated p-ANCA directed against additional target antigens rather than MPO and may be implicated in the pathogenesis of SLE or may be only non-specific antibodies developed in lupus.
Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies.
European Concerted Action on the Immunogenetics of SLE.
Galeazzi M, Morozzi G, Sebastiani GD, Bellisai F, Marcolongo R, Cervera R, De Ramon Garrido E, Fernandez-Nebro A, Houssiau F, Jedryka-Goral A, Mathieu A, Papasteriades C, Piette JC, Scorza R, Smolen J.
Istituto di Reumatologia, Universita di Siena, Italy
Clin Exp Rheumatol 1998 Sep-Oct;16(5):541-6 Abstract quote
OBJECTIVES: To evaluate, in a cohort of 566 patients with systemic lupus erythematosus (SLE) drawn from 11 European centres: (i) the prevalence of ANCAs and their subspecificities in a large series of European SLE patients; (ii) the possible associations of ANCA with the most common clinical manifestations of the disease; and (iii) whether ANCAs correlate with some of the autoantibodies commonly found in SLE.
METHODS: ANCA detection was performed by indirect immunofluorescence (IIF), and by ELISA for lactoferrin (LF), myeloperoxydase (MPO), proteinase3 (PR3) and lysozyme (LZ) subspecificities.
RESULTS: The prevalence of ANCA was 16.4% (IIF). The prevalence of LF was 14.3%, LZ 4.6%, MPO 9.3%, and PR3 1.7%. Our results show that ANCA is associated with certain clinical manifestations of SLE. In particular, positive correlations were found between IIF ANCA and serositis (p = 0.026), livedo reticularis (p = 0.01), venous thrombosis (p = 0.03) and arthritis (p = 0.04), while anti-LF antibodies were associated with serositis (p = 0.05) and livedo reticularis (p < 10(-3). Nevertheless, multivariate analysis demonstrated that other autoantibodies, such as aCL and SSA/Ro, are more closely correlated than ANCA with some of the aforementioned clinical features.
CONCLUSION: Our results demonstrate that ANCA are detectable in SLE sera and that some of them are associated with particular clinical manifestations. Whether ANCA plays a direct pathogenetic role in the vascular damage of SLE or only represents an epiphenomenon or a marker of disease activity remains to be elucidated.
Anti-Phospholipid Antibody and the Lupus Anticoagulant Lupus Band Test
Serum and in vitro production of IL-1 receptor antagonist correlate with C-reactive protein levels in newly diagnosed, untreated lupus patients.
Division of Rheumatology, Allergy and Clinical Immunology, Department of Internal Medicine, Chang Gung Memorial Hospital, Tao-yuan County, Taiwan.
Clin Exp Rheumatol 2001 Sep-Oct;19(5):515-23 Abstract quote
OBJECTIVE: To examine the correlation between C-reactive protein (CRP) and CRP-inducing cytokines (IL-1 beta, IL-6, TNF-alpha) and IL-1 receptor antagonist (IL-1ra), as well as to study their relationship with systemic lupus erythematosus disease activity (SLEDAI) in newly diagnosed, untreated lupus patients.
METHODS: Sera from newly diagnosed untreated lupus and rheumatoid arthritis (RA) patients were examined for CRP and cytokines. Data were compared among patient groups and correlated individually among the lupus group. Lupus monocytes and neutrophils were cultured in vitro to produce IL-1ra and experimental results were related to CRP levels and SLEDAI.
RESULTS: Within lupus, serum CRP, IL-6, IL-1 beta and TNF-alpha levels were significantly lower than those of RA (all p values were < 0.005) and generally higher than those in the controls (p = 0.002, < 0.001, > 0.2, and < 0.001, respectively). Except IL-1ra, which was correlated with CRP (p = 0.045), no substantial correlation was discovered between CRP and IL-6, IL-1 beta or TNF-alpha individually. Moreover, excluding IL-1ra (p = 0.024), there was no association between cytokines and SLEDAI. In vitro IL-1ra as secreted by monocytes correlated with serum CRP and SLEDAI.
CONCLUSION: In lupus patients, serum IL-1 beta, IL-6 or TNF-alpha levels failed to correlate with low CRP levels. This indicates a complicated CRP production process, which can not be explained solely by single cytokines as reported previously. Both serum and in vitro produced IL-1ra may be applied clinically as a surrogate CRP marker in untreated lupus patients as they are both correlated with serum CRP.
CHARACTERIZATION 1997 REVISED CRITERIA FOR CLASSIFICATION OF SYSTEMIC LUPUS ERYTHEMATOSUS
Adapted from Arthritis Rheum 1997;40:1725.
Criterion Definition Malar rash Fixed erythema, flat or raised, over the malar eminences, tending to spare the nasolabial folds Discoid rash Erythematous raised patches with adherent keratotic scaling and follicular plugging; atrophic scarring may occur in older lesions Photosensitivity Skin rash as a result of unusual reaction to sunlight, by patient history or physician observation Oral ulcers Oral or nasopharyngeal ulceration, usually painless, observed by a physician Arthritis Nonerosive arthritis involving two or more peripheral joints, characterized by tenderness, swelling, or effusion Serositis Pleuritis-convincing history of pleuritic pain or rub heard by a physician or evidence of pleural effusion
Pericarditis-documented by electrocardiogram or rub or evidence of pleural effusion
Renal disorder Persistent proteinuria >0.5 g/dl or >3+ if quantitation not performed or
Cellular casts-may be red blood cell, hemoglobin, granular, tubular, or mixed
Neurologic disorder Seizures or psychosis-in the absence of offending drugs or known metabolic derangements, eg uremia, ketoacidosis or electrolyte imbalance Hematologic disorder Hemolytic anemia-with reticulocytosis, or
Leukopenia <4000/mm3 total on two or more occasions, or
Lymphopenia <1500/mm3 on two or more occasions, or
Thrombocytopenia <100 x 10*3/mm3 in the absence of offending drugs
Immunologic disorder Anti-DNA Ab to native DNA in abnormal titer or Anti-Sm or Positive finding of antiphospholipid antibodies based upon:
1) abnormal serum level of IgG or IgM cardiolipin Ab
2) a positive test for lupus anticoagulant using a standard test, or
3) false positive serologic test for syphilis known to be positive for at least 6 months and confirmed by negative Treponema pallidum immobilization or fluorescent antibody absorption test.
Antinuclear antibody Abnormal titer of ANA by IF or equivalent assay at any point in time and in the absence of drugs known to be associated with drug-induced lupus syndrome CLINICAL VARIANTS-SKIN CENTRIPETAL FLAGELLATE ERYTHEMA J Rheumatol 1999;26:692
Variant localized to the trunk and extremities
Br J Dermatol 1998;139:307
May follow Lines of Blashcko
Most cases represent a linear variatn of DLE with a predilection to involve the face
Functional melanonychia due to involvement of the nail matrix in systemic lupus erythematosus.
Skowron F, Combemale P, Faisant M, Baran R, Kanitakis J, Dupin M.
Department of Dermatology, Instruction Military Hospital Desgenettes, Lyon, Laboratory of Pathology, Lyon, Nail Disease Center, Cannes, and Department of Dermatology, Ed. Herriot Hospital, Lyon
J Am Acad Dermatol 2002 Aug;47(2 Pt 2):S187-8 Abstract quote
Longitudinal melanonychia is an unusual finding in systemic lupus erythematosus.
We report the case of a patient of Arabic extraction with cutaneous lesions of lupus erythematosus on the cheek and chest and longitudinal melanonychia affecting several fingers. Results of histologic examination of the skin and direct immunofluorescence analysis confirmed the diagnosis of systemic lupus erythematosus.
The distal matrix revealed changes suggestive of systemic lupus erythematosus accompanied by increased activity of melanocytes but without melanocytic hyperplasia. In this case, longitudinal melanonychia associated with systemic lupus erythematosus was of functional origin.
Lupus erythematosus-associated red lunula.
Wollina U, Barta U, Uhlemann C, Oelzner P.
Department of Dermatology, Institute of Physical Therapy, Friedrich-Schiller-University of Jena, Germany.
J Am Acad Dermatol 1999 Sep;41(3 Pt 1):419-21 Abstract quote
BACKGROUND: Red lunulae have only rarely been described in patients with lupus erythematosus.
OBJECTIVE: We assessed the frequency and classified the type of red lunulae in patients with definite lupus erythematosus seen in an interdisciplinary dermatorheumatologic outpatient clinic.
METHODS: We studied 56 patients with either systemic or cutaneous lupus erythematosus for the presence of red lunulae.
RESULTS: Eleven of 56 patients (19.6%) with lupus erythematosus had red lunulae. All of them showed a complete type of red lunulae, which was seen on all finger nails in 10 patients and on a single finger nail in 1 patient. Seven patients suffered from systemic lupus, the other from subacute cutaneous (n = 2) or chronic discoid cutaneous lupus (n = 2). There was no statistically significant difference in autoantibody expression or treatment regimen between patients with or without red lunulae. However, symptomatic patients had a shorter disease interval, and all but 1 showed either periungual erythema or chilblain lupus. Periungual erythema was not observed in any patient without red lunulae.
CONCLUSION: Red lunulae, although rarely described in the literature, are not an uncommon symptom of patients with lupus erythematosus. They seem to be associated with periungual erythema or chilblain lupus. Red lunulae should be considered in the clinical spectrum of lupus disease.
VARIANTS BY ORGAN SYSTEM BREAST
Cernea SS, Kihara SM, Sotto MN, Vilela MA.
Department of Dermatology, University of Sao Paulo Medical School, Brazil.
J Am Acad Dermatol 1993 Aug;29(2 Pt 2):343-6 Abstract quote
We describe a woman with sclerotic and atrophic lesions of the breast. Histopathologic and immunologic findings indicated a diagnosis of lupus erythematosus.
Lupus mastitis is a rare presentation of panniculitis; only a few cases have been reported in the literature.
Lupus panniculitis (profundus) involving the breast: report of 2 cases and review of the literature.
Holland NW, McKnight K, Challa VR, Agudelo CA.
Department of Internal Medicine, Emory University School of Medicine, Atlanta, GA, USA.
J Rheumatol 1995 Feb;22(2):344-6 Abstract quote
Breast involvement with lupus panniculitis has been infrequently reported.
We describe 2 cases with breast involvement proven by biopsy to be lupus panniculitis. Our review emphasizes the clinical presentation of lupus panniculitis with mastitis and its possible clinical similarity to malignancy. In addition, other connective tissue diseases and vasculitis with breast involvement are noted.
CNS Seizures and psychosis
May be secondary to damage of endothelial cells by antiphospholipid antibodies
HEART Libman-Sacks endocarditis with vegetations attached to the margin of the thickened valve leaflet, on either surface
1-3 mm in size
Myocarditis Coronary artery disease
Increased in patients treated with corticosteroids
JOINTS Nonerosive synovitis with little deformity
Acute phase may have fibrinopurulent exudate
The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and review of Japanese Autopsy Registry Data.
Matsumoto T, Yoshimine T, Shimouchi K, Shiotu H, Kuwabara N, Fukuda Y, Hoshi T.
First Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Hum Pathol 1992 Oct;23(10):1151-8 Abstract quote
We present pathologic findings for 52 livers (51 autopsy specimens and one wedge biopsy specimen) from patients with systemic lupus erythematosus (SLE). Hepatic congestion was the most common disease (40 livers), followed by fatty liver (38), arteritis (11), cholestasis (nine), peliosis hepatis (six), chronic persistent hepatitis (six), nonspecific reactive hepatitis (five), cholangiolitis (four), nodular regenerative hyperplasia of the liver (three), and hemangioma (three). The data obtained here suggest that arteritis of the SLE liver is more common than has been recognized previously. One patient had hepatic infarction complications induced by arteritis.
On the basis of the findings in the present study and a review of the literature, we suggest that hepatic infarction resulting from arteritis is rare in SLE. On the other hand, while occurrence of nodular regenerative hyperplasia of the liver in SLE patients has been considered to be rare, our findings suggest that it may be more common than has been recognized previously. Although congestion and cholestasis may be acute terminal illnesses, fatty change is considered to be specific to the SLE liver. Statistical analysis indicates that exposure to a large dosage of glucocorticoids is a significant factor in the etiology of severe fatty liver.
In addition, our review of Japanese autopsy registry data for 1,468 patients with SLE indicates that the incidence of chronic liver diseases in SLE autopsy cases is as follows: chronic hepatitis, 2.4%; cirrhosis, 1.1%; and liver fibrosis, 0.8%.
Extensive lymphadenopathy as the first clinical manifestation in systemic lupus erythematosus.
Kitsanou M, Andreopoulou E, Bai MK, Elisaf M, Drosos AA.
Department of Internal Medicine, Medical School, University of Ioannina, Greece.
Lupus 2000;9(2):140-3 Abstract quote
Lymphadenopathy (LAP) is a frequent sign of systemic lupus erythematosus (SLE). The lymph nodes are usually soft, nontender, varying in size from 0.5 cm to several centimeters. However, generalized LAP in SLE is extremely rare, while to our knowledge, the presentation of extensive LAP with blocks of retrosternal, mesenteric, and retroperitoneal nodes has not been previously reported as the first clinical manifestation of the disease.
In this report we describe a patient with extensive LAP and active SLE and we point out that generalized LAP should be included among the clinical findings indicating disease activity in SLE patients.
LUNGS Pleuritis and pleural effusions
50% of patients
Chronic interstitial fibrosis
- Lupus erythematosus: Clinical and histopathological study of oral manifestations and immunohistochemical profile of the inflammatory infiltrate.
Department of Dermatology, Medical School, University of São Paulo, Brasil.
- J Cutan Pathol. 2007 Jul;34(7):558-64. Abstract quote
Background: Lupus erythematosus (LE) is a multifactorial autoimmune disease, which may affect the oral mucosa in either its cutaneous and systemic forms, with varied prevalence.
Methods: Forty-six patients with confirmed diagnosis of LE, presenting oral lesions were included in the study. Oral mucosal lesions were analyzed clinically, their histopathological features were investigated and inflammatory infiltrate constitution was assessed using immunohistochemistry against the following clusters of differentiation: CD3, CD4, CD8, CD20, CD68 and CD1a.
Results: From 46 patients with specific LE oral lesions 34 were females (25 with cutaneous LE and nine with systemic LE) and 12 were males (11 with cutaneous LE and one with systemic LE). Clinical aspects of lesions varied, and lips and buccal mucosa were the most affected sites. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement membrane. Inflammatory infiltrate was predominantly composed by T lymphocytes of the CD4 subtype, with a minor prevalence of B lymphocytes, isolated macrophages and rare Langerhans cells.
Conclusions: Oral lesions of lupus erythematosus show a variety of clinical aspects and histologically consist of a lichenoid mucositis with deep inflammatory infiltrate, composed predominantly of T CD4 positive lymphocytes.
- Lupus erythematosus: clinical and histopathological study of oral manifestations and immunohistochemical profile of epithelial maturation.
- Lourenco SV,
- Nacagami Sotto M,
- Constantino Vilela MA,
- Rodrigues Goncalves de Carvalho F,
- Rivitti EA,
- Menta Simonsen Nico M.
Department of Dermatology, Medical School, University of Sao Paulo, Sao Paulo, Brazil.
- J Cutan Pathol. 2006 Oct;33(10):657-62 Abstract quote
Background: Lupus erythematosus (LE) is an autoimmune disease of unknown cause. Prevalence of oral involvement in patients with LE is uncertain but may vary from 9 to 45% in patients with systemic disease and from 3 to 20% in patients with chronic cutaneous involvement.
Methods: Incidence of oral lesions of LE and their clinical aspects were investigated. Their histopathologic features were analyzed, and the status of epithelial maturation was assessed through the expression patterns of cytokeratins.
Results: Twenty-six patients (from 188 examined) presented oral lesions of LE. Most of them were females (19) with systemic disease (11). Clinical aspects of these lesions varied, and lips and buccal mucosa were most affected. Histologically, lesions revealed lichenoid mucositis with perivascular infiltrate and thickening of basement. Cytokeratins profile showed hyperproliferative epithelium, with expression of CK5/6, and CK14 on all epithelial layers, CK16 on all suprabasal layers and CK10 on prickle cell layers only.
Conclusions: Oral lesions of LE show a variety of aspects, and their microscopic features are of a lichenoid mucositis with deep inflammatory infiltrate. Cytokeratins expression patterns are of hyperproliferative epithelium, and this phenomenon must be analyzed in relation to the inflammatory cytokines for a better understanding of the mechanisms of the disease.
Periparotid lupus erythematosus panniculitis. Clinicopathologic correlation of two cases presenting as primary parotid disease.
White WL, Sherertz EF, Berg D, Clark RE.
Department of Pathology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27103.
Arch Pathol Lab Med 1993 May;117(5):535-9 Abstract quote
Lupus erythematosus (LE) panniculitis, also called lupus profundus, is an uncommon but well-established manifestation of both chronic cutaneous (discoid) LE and systemic LE. Although LE panniculitis characteristically may involve the face, specific parotid and periparotid involvement has not, to the best of our knowledge, been previously reported.
We describe the clinicopathologic correlation of two cases of LE panniculitis that presented as apparent primary parotid parenchymal disease; one as a neoplasm, the other as parotiditis. Failure to recognize LE panniculitis resulted in prolonged periods of inappropriate therapy and significant morbidity, including an unnecessary parotidectomy.
Lupus erythematosus panniculitis has well-established histologic criteria that should be considered in the differential diagnosis of an unexplained parotid mass.
SEROSAL MEMBRANES Pericarditis Peritonitis SKIN Butterfly erythematous rash along the bridge of nose and cheeks-may occur on any location
50% of patients
Exacerbated by sunlight
Interface dermatitis with Ig and complement deposited along the dermoepidermal junction
HISTOLOGICAL TYPES CHARACTERIZATION ANA-NEGATIVE LE About 5% of patients
Antiphospholipid antibodies: a disease marker in 25 patients with antinuclear antibody negative systemic lupus erythematosus (SLE). Comparison with a group of 91 patients with antinuclear antibody positive SLE.
Meyer O, Piette JC, Bourgeois P, Fallas P, Bletry O, Jungers P, Kahn MF, Godeau P, Ryckewaert A.
J Rheumatol 1987 Jun;14(3):502-6 Abstract quote
Twenty-five antinuclear antibody (ANA) negative patients with systemic lupus erythematosus (SLE) or lupus-like disease were compared to 91 ANA positive patients with SLE for clinical and biological symptoms.
Cutaneous symptoms were infrequent in ANA negative patients (p less than 0.03). Thrombocytopenia (p less than 0.001), venous or arterial thrombosis (p less than 0.02) as well as cerebral infarction (p less than 0.001) were more frequent.
Three types of antiphospholipid antibodies were determined by different methods; the VDRL, the lupus anticoagulant and an ELISA for IgG anticardiolipin antibody (aCL). The frequency of a positive VDRL test was significantly higher in the ANA negative group (p less than 0.05). Correlation studies suggest that the 3 methods are not redundant and detect overlapping but not identical antibodies.
Of the 3 antiphospholipid antibody assays, only the IgG aCL test was significantly associated with thrombosis in the ANA negative group (p less than 0.02).
Am J Dermatopathol 1999;21:129
Clin Exp Rheumatol 1999;17:63
Vascular disease involving the skin, heart, pulmonary, and nervous systems
Endothelial localization of Ro/SSA antigen and correlation of C5b-9 serum levels with evidence of active CNS disease suggesting that humoral injury mediated by anti-Ro/SSA antibody binding to endothelial Ro antigen may be occurring
Am J Dermatopathol 1999;21:129
Interface dermatitis with superficial vasculopathic changes similar to dermatomyositis with telangiectasia, endothelial cell necrosis, luminal deposits of fibrin, and vascular density reduction
Lymphocytic vasculitis, leukocytoclastic vasculitis, and pauci-inflammatory thrombotic vasculopathy
CHILLBLAINS LUPUS ERYTHEMATOSUS
Hum Pathol 1997;28:478
Vasculopathic lesions presenting as palpable purpura, ulcers, digital infarcts, and perniotic lesions of the fingers and toes
Vacuolar interface dermatitis with variable epidermal atrophy
Striking lymphocytic vascular reaction involving the venules throughout the dermis
Mural and luminal fibrin deposition within reticular dermal based blood vessels
Association between this disease and anti-Ro/SSA antibodies
Chillblains unassociated with SLE has striking dermal papillary edema without fibrin deposits within vessels
Clinical and histopathologic features and immunologic variables in patients with severe chilblains. A study of the relationship to lupus erythematosus.
Viguier M, Pinquier L, Cavelier-Balloy B, de la Salmoniere P, Cordoliani F, Flageul B, Morel P, Dubertret L, Bachelez H.
Institut de Recherche sur la Peau et Service de Dermatologie, Hopital Saint-Louis, 1 avenue Claude Vellefaux, 75010 Paris, France.
Medicine (Baltimore) 2001 May;80(3):180-8 Abstract quote
We investigated 33 patients affected with chilblain lesions following a persisting course of more than 1 month.
We focused on the incidence of an underlying connective tissue disease, mostly lupus erythematosus (LE), and we analyzed features of idiopathic chilblains compared with those of chilblain lesions associated with connective tissue disease. We also carried out a prospective follow-up of patients.
Eleven patients included in the study were free of any clinical and/or laboratory abnormality suggestive of connective tissue disease, while 22 of 33 patients showed 1 or several abnormalities raising suspicion for connective tissue disease, and among them 8 had a diagnosis of systemic lupus erythematosus (SLE) established at initial evaluation based on the American College of Rheumatology revised criteria. The comparative analysis of patients with idiopathic chilblains and patients with chilblains associated with LE showed that female sex and persistence of lesions beyond cold seasons were significantly associated with chilblain LE.
Histopathologic studies of chilblain lesions did not reveal features typical of LE in any case, but revealed a higher incidence of a deep perisudoral infiltrate in idiopathic chilblains. In patients showing signs of connective tissue disease, positive cutaneous immunofluorescence was correlated with the presence of circulating antinuclear antibodies. Two patients had an ascertained diagnosis of SLE with severe manifestations during prospective follow-up, requiring treatment with oral steroids in both cases.
Chilblains following a chronic course may reveal connective tissue disease, and patients affected with chilblains associated with autoimmune abnormalities may develop severe SLE. Accordingly, long-term follow-up of these patients is warranted.
Systemic lupus erythematosus with C1q deficiency.
Stone NM, Williams A, Wilkinson JD, Bird G.
Department of Dermatology, Department of Immunology, Oxford Radcliffe Hospital, Old Road, Headington, Oxford OX3 7LJ, U.K.
Br J Dermatol 2000 Mar;142(3):521-4 Abstract quote
We report a case of systemic lupus erythematosus associated with C1q deficiency. Our patient presented at the age of 6 years with cutaneous lupus. She later developed Raynaud's phenomenon, non-scarring alopecia, oral ulceration and grand mal seizures due to cerebral vasculitis.
Complement C3 and C4 levels were consistently normal during flares of her lupus and haemolytic activity of her complement was absent, suggesting a deficiency of an early component of the complement cascade. No C1q could be detected.
Lupus erythematosus associated with genetically determined deficiency of the second component of the complement.
Lipsker DM, Schreckenberg-Gilliot C, Uring-Lambert B, Meyer A, Hartmann D, Grosshans EM, Hauptmann G.
Clinique Dermatologique, 1 Place de l'Hopital, F-67091 Strasbourg Cedex, France.
Arch Dermatol 2000 Dec;136(12):1508-14 Abstract quote
BACKGROUND: The gene deletion responsible for the type I human complement C2 deficiency was reported in 1992. The purpose of our study is to evaluate clinical and immunological characteristics of 11 patients with lupus erythematosus and type I C2 deficiency.
OBSERVATIONS: We observed 5 patients with a homozygous C2 deficiency and 6 with a heterozygous C2 deficiency. Eight patients had systemic lupus erythematosus, 2 had subacute cutaneous lupus erythematosus, and 1 had chronic lupus erythematosus. Photosensitivity was present in 73% of the patients, and 64% tested positive for anti-Ro (SSA) antibodies. Renal involvement that required immunosuppressive therapy was present in 54% of the patients. Ninety percent of the patients tested positive for antinuclear antibodies, and 54% tested positive for anti-double-stranded DNA antibodies. Phenotyping of the fourth component of the complement was performed in 82% of the patients and showed a C4A4B2 phenotype, which is suggestive for the type I C2 deficiency.
CONCLUSIONS: Most patients with lupus erythematosus associated with C2 type I deficiency are photosensitive, and this is probably related to the presence of anti-Ro (SSA) autoantibodies. The prognosis for those patients is not better than that for patients with lupus erythematosus in general.
Lymphocyte rich interface dermatitis
Less epidermal atrophy than SCLE; sometimes acanthosis
Prominent basement membrane zone thickening
Prominent follicular hyperkeratosis
Dense superficial and deep perivascular and periadnexal infiltrates
Prominent follicular degneration
Pronounced dermal mucin usually present
Pronounced florid lymphoid hyperplasia may be present
Pediatr Dermatol 1999;16:128
Br J Dermatol 1998;139:307
Lesions are confined mainly to the skin, usually on face and scalp
Adherent scale with prominent keratotic follicular plugs similar to carpet tacks-tintack sign
Itchy lesions may lead to prurigo nodularis
Discoid lesions may manifest in seborrheic dermatitis like distribution
Linear lesions following the lines of Blaschko may occur
Pigmentary alteration may be striking
Oral cavity in 15%
SLE develops in 5-10% of patients
ANA positive in 35%
Discoid lupus erythematosus presenting as asymmetric posterior blepharitis.
Gloor P, Kim M, McNiff JM, Wolfley D.
Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06520-8061, USA.
Am J Ophthalmol 1997 Nov;124(5):707-9 Abstract quote
PURPOSE: To describe the ophthalmic findings of patients with discoid lupus erythematosus.
METHOD: We describe two women who originally were thought to have asymmetric posterior blepharitis; however, the involved eyelid also had an erythematous, scaly cutaneous lesion.
RESULT: In both patients, histology and immunofluorescence studies performed on cutaneous biopsy specimens established the diagnosis of discoid lupus erythematosus.
CONCLUSIONS: It is important to diagnose discoid lupus of the eyelids because misdiagnosis can delay treatment and thus lead to deformities of the eyelid margin. Misdiagnosis can also lead to a complicated full-thickness eyelid biopsy and delay the diagnosis of systemic lupus erythematosus.
FOLLICULOTROPIC LE Perifollicular and perivascular inflammation without interfollicular interface dermatitis
Abundant dermal mucin
Absence of tissue eosinophils
Serology and lupus band testing are usually negative
No extracutaneous stigmata to suggest a systemic connective tissue disease diathesis
Dermatol Surg 1995;21:255
Prominent acanthosis may be present in older lesions and may simulate squamous cell carcinoma
- Cutaneous lupus erythematosus simulating squamous neoplasia: the clinicopathologic conundrum and histopathologic pitfalls.
Department of Pathology, University of North Carolina Hospitals, Chapel Hill, North Carolina, USA.
- J Am Acad Dermatol. 2007 Jun;56(6):1013-20. Abstract quote
BACKGROUND: The clinical distribution and character of cutaneous lupus erythematosus lesions can simulate squamous neoplasms, leading physicians to submit a shave biopsy specimen with a differential diagnosis of squamous neoplasm.
OBJECTIVE: Our aim was to describe histologic features of interface dermatitis that cause difficulty in distinguishing between cutaneous lupus erythematosus and squamous neoplasia in shave biopsy specimens and to identify distinguishing criteria.
METHODS: Twenty-six biopsy specimens from 10 patients initially diagnosed with squamous neoplasia that ultimately proved to be cutaneous lupus erythematosus were identified. Comparisons were made of these to 38 control biopsies of chronic cutaneous lupus erythematosus and 34 control biopsies of keratoses/carcinomas without lupus. All biopsies were scored (0 or 1: absent or present) with respect to 11 histologic criteria.
RESULTS: The criteria of perifollicular inflammation, follicular plugging, vacuolar interface change, compact orthokeratosis, and acrosyringeal inflammation were significantly more common in the lupus cases than in the keratoses/carcinomas controls. The mean lupus case score was 6.88, lupus control score 6.55, and keratoses/carcinomas control score 5.08.
LIMITATIONS: A limited number of patients were studied. Microscopic observations and assumptions with inherent subjectivity were used in establishing the histologic scores.
CONCLUSION: Use of the criteria presented, although not absolute, should alert one to the possibility of lupus in an atypical squamous proliferation, especially in suspected squamous neoplasms that worsen or recur after therapy.
Hypertrophic lupus erythematosus: a clinicopathological study of 14 cases.
Daldon PE, De Souza EM, Cintra ML.
Department of Dermatology, and Department of Pathology, State University of Campinas - UNICAMP, Campinas/SP, Brazil.
J Cutan Pathol. 2003 Aug;30(7):443-8. Abstract quote
BACKGROUND: Hypertrophic lupus erythematosus (HLE) is a distinct and rare subset of lupus erythematosus (LE). It is characterized by verrucous lesions, chronic in its course, and resistant to treatment. The purpose of this study was to identify clinical and histological characteristics of HLE.
METHODS: We review our experience with 14 cases of HLE identified in a group of 220 patients with different forms of LE, at the UNICAMP Hospital, between 1976 and 2002.
RESULTS: All patients presented verrucous plaques concomitantly with discoid lesions. The most common sites of involvement were the face and the arms. Histology of HLE lesions revealed pseudoepitheliomatous hyperplasia engulfing elastotic material. Elastic fibers were seen in migration throughout the epidermis. Classic features of LE were noted in all cases. Three of the patients developed hyperkeratotic papules with central keratinous plug on their arms at the previous LE sites. These lesions resemble clinically and histopathologically keratoacanthomas. In one patient, HLE lesion progressed to squamous cell carcinoma (SCC), 26 years after the onset of the disease.
CONCLUSIONS: Transepithelial elimination of the elastotic material may be a feature of HLE. Some HLE lesions may present as keratoacanthoma, but classical features of LE aid the correct diagnosis. SCC may arise on a long-standing HLE lesion; therefore HLE requires clinical and histopathological follow up.
Amyloid deposition is frequently observed in skin lesions of hypertrophic lupus erythematosus.
Khan MA, Maruno M, Khaskhely NM, Uezato H, Nonaka S.
Department of Dermatology, Faculty of Medicine, University of the Ryukyus, Nishihara, Okinawa, Japan
J Dermatol. 2002 Oct;29(10):633-7. Abstract quote
Four cases of Hypertrophic Lupus Erythematosus (HLE) were reported. The lesions of HLE were observed on the forearms, face and hands in all four cases. Clinically, the lesions were erythematous, hyperkeratotic plaques.
The clinical course was marked by chronicity and progression of the lesion. Histologically, marked hyperkeratosis, parakeratosis, acanthosis, degenerative changes of basal cells in H/E stain, and thickened, multilayered basement membrane in PAS stain, were observed. The observations of Dylon stain revealed that localized amyloid deposition was observed in all four cases of HLE lesions, as fluorescent-orange colored amyloid deposits in the papillary dermis and subepidermal areas at near orjust below the dermo-epidermal junction appeared under fluorescent microscope.
On the basis of clinical and histological observations, we suggest that chronic irritation, such as sunlight exposure over a long-duration, might have caused the characteristic abnormalities at the dermo-epidermal junction and also initiated the frequency of amyloid deposits locally secondary to the diseases.
We compared our HLE cases to other types of lupus erythematosus (LE) skin lesions, as to whether deposition of amyloid materials were frequently observed or not. Amyloid deposition was observed in one case of DLE and none of the SLE cases. Localized amyloid deposition was more frequently observed in skin lesions, secondary to HLE disease, as compared to other types of LE.
Hypertrophic discoid lupus erythematosus of the conjunctiva.
Uy HS, Pineda R 2nd, Shore JW, Polcharoen W, Jakobiec FA, Foster CS.
Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts 02114, USA.
Am J Ophthalmol 1999 May;127(5):604-5 Abstract quote
PURPOSE: To report the ophthalmic manifestations of hypertrophic discoid lupus erythematosus of the conjunctiva.
METHOD: Case report and review of biopsy results.
RESULTS: A 58-year-old woman with a history of chronic blepharoconjunctivitis presented with an unusual raised conjunctival lesion. Previous biopsy slides were reviewed and interpreted as diagnostic of discoid lupus erythematosus, hypertrophic or verrucous type. Both blepharoconjunctivitis and the raised conjunctival lesion resolved with hydroxychloroquine therapy.
CONCLUSIONS: A raised conjunctival mass in the context of refractory blepharoconjunctivitis should elicit suspicion for discoid lupus erythematosus. The hypertrophic variant of this disease can affect the conjunctiva.
DRUG INDUCED LUPUS ERYTHEMATOSUS DRUGS Hydralazine, procainamide, D-penicillamine
Rheum Dis Clin North Am 1994;20:61
J Clin Invest 1991;88:680
Hydralazine, procainamide, isoniazid, D-penicillamine are the classic drugs associated with the disease
Chlorpromazine and hydralazine: Antihistone antibodies
Procainamide and quinidine: Anti-H2a-H2b DNA antibodies
Systemic symptoms usually sparing the central nervous system and kidney
Skin disease is less frequent and pulmonary disease more common than in idiopathic SLE
Association with anti-histone Ab
Dermatol Clin 1999;17:537
Drugs associated with Lupus Erythematosus:
Drug-Induced, Ro/SSA-Positive Cutaneous Lupus Erythematosus.
Srivastava M, Rencic A, Diglio G, Santana H, Bonitz P, Watson R, Ha E, Anhalt GJ, Provost TT, Nousari CH.
Division of Dermatopathology, Department of Dermatology, University of Pennsylvania, Philadelphia, PA 19104.
Arch Dermatol 2003 Jan;139(1):45-9 Abstract quote
OBJECTIVE: To study the clinical and immunopathologic findings of drug-induced, Ro/SSA-positive cutaneous lupus erythematosus (CLE). DESIGN: Retrospective medical and laboratory record review.
SETTING: Immunodermatology Division of Johns Hopkins Hospital (Baltimore, Md).
PATIENTS: Of 120 patients found to have anti-Ro/SSA antibodies by hemagglutination and/or double immunodiffusion, 70 had clinical and immunopathologic confirmation of CLE. Fifteen of these 70 patients had a history of new drug exposure, defined as less than 6 months, associated with disease development.
RESULTS: The disease-associated drugs included hydrochlorothiazide (5 patients), angiotensin-converting enzyme inhibitors (3 patients), calcium channel blockers (3 patients), interferons (2 patients), and statins (2 patients). The most common presentations were photodistributed diffuse erythema and subacute CLE-type lesions without evidence of significant systemic disease. All specimens revealed interface dermatitis and fine granular IgG deposition along the basement membrane zone and throughout the epidermis. Most patients experienced improvement or resolution of clinical lesions within 8 weeks and decrease of Ro/SSA titers within 8 months after discontinuation of drug treatment.
CONCLUSIONS: Antihypertensive drugs are the most commonly associated with Ro-positive CLE. Clinical and immunopathologic features of this drug-induced variant do not seem to differ from the idiopathic disease. In most cases, the disease improves or resolves on discontinuation of the offending drug treatment. It is not known if these drugs precipitate disease in patients who have subclinical disease. Drug-induced Ro/SSA-positive CLE should be included on the differential diagnosis in patients presenting with photosensitive or subacute CLE-type eruptions.
Drug-Induced Lupus Associated With COL-3 Report of 3 Cases
Jayashri V. Ghate, etal.
Arch Dermatol. 2001;137:471-474 Abstract quote
Anti-angiogenesis is an exciting new approach to anticancer therapy. COL-3, a tetracycline derivative, is a novel anti-angiogenesis agent with potent preclinical anticancer activity. During the conduct of a phase 1 clinical trial for refractory metastatic cancer at the National Institutes of Health, we observed 3 individuals who developed phototoxicity followed by clinical and laboratory features of drug-induced lupus.
Three of 35 patients treated with COL-3 developed sunburnlike eruptions accompanied by fever and a positive antinuclear antibody titer within 8 to 29 days of starting treatment. Two of 3 had positive antihistone antibody levels and arthralgia. One patient had marked systemic manifestations including pulmonary infiltrates and elevated erythrocyte sedimentation rate remittent for more than 1 year after discontinuing COL-3 treatment. The other 2 patients' symptoms and rash abated within 2 weeks of discontinuing therapy although the serologic markers remained abnormal for the duration of follow-up.
COL-3 is the second tetracycline derivative to be implicated in the development of drug-induced lupus. A sunburnlike eruption immediately preceded or accompanied the systemic and serologic changes in these 3 patients. The rapid onset and the phototoxic appearance of the accompanying eruptions might suggest that damage to the keratinocytes caused the formation of neoantigens to which autoantibodies formed.
Drug-induced cutaneous lupus erythematosus, a distinct syndrome that is frequently unrecognized
Jeffrey P. Callen, MD
J Am Acad Dermatol 2001;45:315-316 Article Quote of First Paragraph
Avariety of drugs have been linked to syndromes that resemble lupus erythematosus (LE). Until recently it befuddled me why dermatologists needed to know about drug-induced LE (DIL), a disease that rarely has cutaneous manifestations. DIL resembles systemic LE (SLE) but has several distinctive features. One of these is the presence of antihistone antibody, an antibody that is fairly specific for DIL. However, with the recent linkage of minocycline as a cause of DIL, it is now important that dermatologists recognize this syndrome. DIL differs from drug-induced subacute cutaneous LE (DI-SCLE), a syndrome that I believe is under-recognized.
Drug-induced systemic lupus erythematosus associated with etanercept therapy.
Shakoor N, Michalska M, Harris CA, Block JA.
Lancet 2002 Feb 16;359(9306):579-80 Abstract quote
Specific antagonists of tumour necrosis factor (TNF)-alpha have rapidly gained popularity for the treatment of rheumatoid arthritis. The monoclonal antibody against TNF-alpha, infliximab, has been associated with induction of systemic lupus erythematosus (SLE); however, there have been no published reports of drug-induced SLE associated with the soluble TNF-alpha receptor etanercept.
We describe four female patients who developed signs and symptoms of SLE during treatment with etanercept; in two SLE was unambiguous. On diagnosis of SLE, etanercept was discontinued and the SLE-related symptoms promptly resolved. Etanercept should be considered in the list of agents associated with drug-induced SLE.
LUPUS ERYTHEMATOSUS PROFUNDUS
J Am Acad Dermatol 1981;5:673
Arch Dermatol 1983;119:61
Infiltration of fat lobule by lymphocytes, histiocytes, and plasma cells with interposed zone of granular necrobiotic alteration
Nodules of centroblasts and centrocytes with admixed tingible body macrophages recapitulate lymphoid follicles
Endothelial necrosis, segmental deposits of fibrin, occlusive luminal thrombi of interstitial capillaries and venules and obliterative lymphocytic angiotropism
A significant percentage may manifest lymphoid atypia making distinction from subcutaneous T-cell lymphoma difficult
A positive Lupus Band test will occur if there is concomitant interface changes and when LEP arises with symptomatology indicative of SLE
Lupus erythematosus panniculitis: clinicopathological, immunophenotypic, and molecular studies.
Park HS, Choi JW, Kim BK, Cho KH.
Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
Am J Dermatopathol. 2010 Feb;32(1):24-30. Abstract quote
Lupus erythematosus panniculitis (LEP) is an inflammatory disorder of the subcutaneous fat in patients with lupus erythematosus (LE). It is a rare variant of the disease, which occurs approximately in 1%-3% of patients with cutaneous LE.
The purpose of this study was to investigate the clinical, histopathologic, immunophenotypical, and molecular profiles of LEP. We performed a retrospective study of 19 biopsy specimens from 17 patients with LEP. We reviewed their clinical data and reexamined the histopathology. Immunophenotyping and molecular studies were done using sections from paraffin-embedded formalin-fixed tissue. The most common clinical manifestation was a depressed patch on upper arm. Patients showed good response to variable treatment modalities, but, generally, relapse of panniculitis was noted when treatment was discontinued.
Histopathologically, most specimens revealed lymphoplasmacytic lobular panniculitis with epidermal and dermal changes of LE, hyaline fat necrosis, and lymphoid follicles. Immunohistochemistry showed a mixture of T and B cells in dermis and subcutis with a slight preponderance of T cell. Although the polymerase chain reaction analysis of the T-cell receptor-gamma gene rearrangement showed a polyclonal smear in 89.5% of cases, a small portion of specimens demonstrated monoclonality.
LEP is a chronic recurrent disease with characteristic features. Its diagnosis is often challenging, and a precise diagnosis is achievable only upon elaborate clinicopathologic correlation and integrated interpretation of all diagnostic criteria.
- Lupus erythematosus panniculitis (lupus profundus): Clinical, histopathological, and molecular analysis of nine cases.
Massone C, Kodama K, Salmhofer W, Abe R, Shimizu H, Parodi A, Kerl H, Cerroni L.
Department of Dermatology, Medical University of Graz, Graz, Austria.
: J Cutan Pathol. 2005 Jul;32(6):396-404. Abstract quote
Background: The diagnosis of lupus erythematosus panniculitis (LEP) may be very difficult in cases in which involvement of the subcutaneous fat is the only manifestation of the disease. The main differential diagnosis is subcutaneous panniculitis-like T-cell lymphoma (SPTCL).
Methods: We performed a retrospective study reviewing the histopathologic features of 11 biopsy specimens from nine patients with LEP (M : F = 2 : 7; median age: 48 years; range: 20-71 years).
Results: Histopathologically, all biopsies revealed a lobular panniculitis, with concomitant septal involvement in 82% of them. Dermal changes included the presence of superficial and deep infiltrates (82%) and mucin deposition (73%). The majority of cases (73%) presented also some form of epidermal involvement. The subcutaneous infiltrate was composed of lymphocytes in all cases, admixed with plasma cells in 91% of cases. Lymphoid follicles with reactive germinal centers were detected in 45% of cases. Immunohistochemistry showed a predominance of alpha/beta-T-helper and cytotoxic lymphocytes in 80% of cases admixed with B lymphocytes. The polymerase chain reaction analysis of the T-cell receptor (TCR)-gamma gene showed a polyclonal smear in all cases.
Conclusions: Our study shows that the most useful histopathologic criteria for distinguishing LEP from SPTCL are the presence of involvement of the epidermis, lymphoid follicles with reactive germinal centers, mixed cell infiltrate with prominent plasma cells, clusters of B lymphocytes, and polyclonal TCR-gamma gene rearrangement.
J Am Acad Dermatol 1981;5:673
Arch Dermatol 1983;119:61
Head and neck, upper arms, trunk, and buttocks
Tan to violaceous plaques
Women 3-5th decades, occasional infant cases
May herald onset of LE or occur in isolation but usually occurs simultaneously with other cutaneous and extracutaneous manifestations
Occurs with about equal frequency with both DLE and SLE though other studies doubt this with SLE-affects about 1-2% of LE patients
Pediatr Dermatol 1999;16:273
Pediatric patients with antiphospholipid syndrome and/or hereditary complement deficiency may present with this
Lupus erythematosus panniculitis: an immunohistochemical study.
Riccieri V, Sili Scavalli A, Spadaro A, Taccari E, Zoppini A.
Institute of Rheumatology, University La Sapienza, Rome, Italy.
Clin Rheumatol 1994 Dec;13(4):641-4 Abstract quote
An immunohistochemical study on a case of lupus erythematosus panniculitis (LEP), without discoid lupus erythematosus (DLE) or systemic lupus erythematosus (SLE) signs, showed that the cells in skin infiltrates were immunologically committed lymphocytes (OKT4, OKT8, OKT11 and HLA-DR positive cells) and elements of the monocyte-macrophage lineage (Leu M3 and Leu M5 positive).
No immunophenotypically identifiable B-lymphocytes were seen. Immunofluorescent IgG, IgM, C3 and C4 deposits were found in blood vessel walls of the deep dermis.
These findings, similar to that described in the skin changes of SLE and DLE, suggest that immunological mechanisms are operative in localized LEP, where the dermal lesions are the only expression of the disease.
Generalized lupus erythematosus profundus in a patient with genetic partial deficiency of C4.
Nousari HC, Kimyai-Asadi A, Provost TT.
Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Am Acad Dermatol 1999 Aug;41(2 Pt 2):362-4 Abstract quote
Lupus erythematosus profundus (LEP) is an unusual variant of cutaneous lupus erythematosus (CLE)that is characterized by chronic, recurrent inflammation of the subcutaneous tissue leading to fibrosis. It is found in the settings of both discoid and systemic lupus erythematosus. Generalized forms are extremely rare.
We present a case of generalized LEP associated with genetic partial C4-deficiency.
LYMPHOMATOID LUPUS ERYTHEMATOSUS
Am J Dermatopathol 1997;19:446
Int J Dermatol 1994;33:157
Folliculotropic pattern presents with indurated follicular papules in malar area versus infiltrative transient urticarial plaques in upper back and anterior chest
Dense lymphoid infiltrates in perifollicular and perivascular array with minimal involvement of the interfollicular epidermis (folliculotropic lymphomatoid DLE)
Resembles lichenoid SCLE but the bandlike infiltrate is of greater intensity with foci of striking epitheliotropism and numerous Sezary cells
Mimicing an angioimmunoproliferative lesion with dense angiocentric lymphoid infiltrates with thrombosis-atypical lymphocytes with polylobated nuclear contours-associated with interface dermatitis
Dense infiltration of fat lobule with lymphocytes with variable atypia and fat necrosis
NEONATAL LUPUS ERYTHEMATOSUS Associated with heart block
Similar to SCLE
Histopathological characteristics of neonatal cutaneous lupus erythematosus: description of five cases and literature review.
Y. Penate, etal.
J Cutan Pathol 2009;36:660-667
Neonatal lupus erythematosus. A clinical, serological and immunogenetic study with review of the literature.
Watson RM, Lane AT, Barnett NK, Bias WB, Arnett FC, Provost TT.
Medicine (Baltimore) 1984 Nov;63(6):362-78 Abstract quote
Neonatal lupus erythematosus (NLE) is an inflammatory disorder of neonates characterized by transient cutaneous lesions and/or congenital heart block.
The cutaneous lesions usually heal with minimal scarring, but healing may be delayed for many months in occasional cases. Photosensitivity is recognized as a component of this syndrome. A large proportion of this maternal population is asymptomatic, although the mothers' potential risk for developing CTD in the future remains to be determined. Moreover, this maternal group may exhibit a tendency to fetal wastage. La(SSB) and/or Ro(SSA) antibody is almost universally present in the sera of the neonatal lupus mothers and their infants.
Since these antibodies may have a pathogenetic role in NLE, screening of infants with isolated CHB and/or cutaneous lesions suggestive of LE, and their mothers, for the presence of Ro(SSA) and La(SSB) antibodies is strongly recommended. HLA studies reveal that infants of Ro-positive mothers bearing the HLA, A1, B8, DR3, MB2 and MT2 phenotypes are at increased risk of developing neonatal lupus, in sharp contrast to infants of Ro-positive mothers bearing the DR2 and/or MB1/MT1 phenotypes.
Recognition of the protean manifestations of this complex disorder by obstetricians, pediatricians, cardiologists, and dermatologists will undoubtedly lead to increased detection of NLE and afford further opportunity to elucidate more fully the etiology of this syndrome.
Neonatal lupus erythematosus syndrome.
Maynard B, Leiferman KM, Peters MS.
Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905.
J Cutan Pathol 1991 Oct;18(5):333-8 Abstract quote
Three cases of neonatal lupus erythematosus (NLE) syndrome are described.
The key diagnostic sign is the erythematous and annular clinical appearance of lesions. The histopathologic findings may be subtle in NLE syndrome compared with discoid or subacute cutaneous lupus erythematosus. Direct immunofluorescence testing may be useful in supplementing the histopathologic evaluation. Detection of immunoglobulins, complement, or both at the basement membrane zone in lesional skin by immunofluorescence occurs in approximately half of cases; a negative study does not preclude the diagnosis of NLE syndrome.
Clinical and serologic evaluation of both the infant and the mother are important in establishing a diagnosis of NLE syndrome, particularly when histopathologic findings are subtle.
Neonatal lupus erythematosus.
Department of Dermatology, University of Colorado School of Medicine, Denver.
J Invest Dermatol 1993 Jan;100(1):9S-13S Abstract quote
Neonatal lupus erythematosus (NLE) is an autoimmune disease whose major findings are subacute cutaneous lupus erythematosus (SCLE) skin lesions and congenital heart block.
Babies have maternal anti-Ro/SSA, anti-La/SSB, or anti-U1RNP autoantibodies. Anti-Ro/SSA are the predominant autoantibodies, having been found in about 95% of cases. The autoantibodies pass through the placenta from mother to child. Skin disease resolves at about the time that maternal autoantibodies can no longer be detected in the baby. NLE therefore provides the strongest clinical evidence that autoantibodies are involved in at least some manifestations of lupus erythematosus, but there is as yet no definitive evidence implicating autoantibodies in the disease process.
Skin disease usually begins after birth, is transient, and does not result in scarring. Cardiac disease begins in utero, and the heart block is almost always permanent. Many babies require pacemakers, and about 10% die from complications related to cardiac disease. In some cases, transient liver disease or thrombocytopenia have been observed. Individuals who had NLE usually have healthy childhoods but may develop autoimmune disease in adulthood. Whether the later development of autoimmune disease is a common or an unusual event is not yet known. Mothers of babies with NLE may be asymptomatic initially, but with time usually develop symptoms of autoimmune disease.
The most typical constellation of symptoms in our group of approximately 30 mothers of babies with NLE is that of Sjogren's syndrome. Most babies exposed to anti-Ro/SSA autoantibodies during gestation will not develop NLE. There is no test to determine prospectively which babies will be affected.
Treatment during gestation is still controversial and, if attempted, should be reserved for fetuses with potentially life-threatening disease. Treatment after birth consists of topical management for skin disease and pacemaker implantation, if necessary, for heart block. Systemic steroids may be given for serious internal disease.
La (SS-B)-positive neonatal lupus erythematosus: report of a case with unusual features.
Neidenbach PJ, Sahn EE.
Department of Dermatology, Medical University of South Carolina, Charleston 29425-2215.
J Am Acad Dermatol 1993 Nov;29(5 Pt 2):848-52 Abstract quote
Neonatal lupus erythematosus is most often associated with autoantibodies against Ro and La antigens. Rarely, neonatal lupus erythematosus occurs in the absence of Ro antibody.
We present a case of La antibody-positive neonatal lupus erythematosus with unusual features.
Neonatal lupus erythematosus.
Jenkins RE, Kurwa AR, Atherton DJ, Black MM.
St John's Institute of Dermatology, St Thomas' Hospital, London, UK.
Clin Exp Dermatol 1994 Sep;19(5):409-11 Abstract quote
We present a case of neonatal lupus erythematosus (NLE) in a black infant presenting with symmetrical depigmented macules on the face resembling vitiligo. NLE is a rare condition affecting newborn infants of mothers who have connective tissue disease, with or without autoantibodies to extractable nuclear antigens Ro (SS-A), La (SS-B) or ribonucleoproteins. Infants present with cutaneous lesions or congenital heart block or both.
The skin lesions are usually annular and erythematous and transient and resemble those of subacute cutaneous lupus erythematosus. The presentation of this patient was therefore striking.
Neonatal lupus erythematosus: discordant disease expression of U1RNP-positive antibodies in fraternal twins--is this a subset of neonatal lupus erythematosus or a new distinct syndrome?
Solomon BA, Laude TA, Shalita AR.
Department of Dermatology, State University of New York-Health Science Center at Brooklyn 11203, USA.
J Am Acad Dermatol 1995 May;32(5 Pt 2):858-62 Abstract quote
Neonatal lupus erythematosus (NLE) is an uncommon disease that is manifested by cutaneous lesions, cardiac conduction defects, or both, that appear in utero or shortly after birth. In approximately 95% of patients, anti-Ro antibody (Ro[SS-A]) has been identified and has become the serologic marker for NLE. Since 1987 there have been four reported cases of Ro- and anti-La antibody (La[SS-B])-negative, U1RNP antibody-positive, NLE.
Our affected twin, as well as all other infants with U1RNP-positive NLE, had cutaneous lesions similar to those in Ro-positive NLE, although they lacked systemic abnormalities, including cardiac conduction defects. HLA typing of mothers with infants with U1RNP-positive NLE revealed the presence of HLA-DR4, DQw1, or DQw3 phenotypes. Our typing confirms these findings. As with Ro-positive NLE, no distinct HLA associations were demonstrated in the infants. Unlike Ro-positive mothers, all mothers with a U1RNP-positive infant with NLE had connective tissue disease at the time of the diagnosis and had a different spectrum of disease.
We describe the clinical, serologic, and immunogenetic findings in the first reported case of U1RNP-positive NLE in dizygotic twins in whom the NLE disease expression was discordant.
Cutaneous telangiectases in neonatal lupus erythematosus.
Thornton CM, Eichenfield LF, Shinall EA, Siegfried E, Rabinowitz LG, Esterly NB, Lucky AW, Friedlander SF.
Division of Dermatology, University of California, San Diego, USA.
J Am Acad Dermatol 1995 Jul;33(1):19-25 Abstract quote
BACKGROUND: Persistent telangiectases are a feature of neonatal lupus erythematosus (NLE) but have generally been noted in areas of prior inflammatory disease. The occurrence of vascular macules and papules at sites without preceding dermatitis has not been reported in NLE.
OBJECTIVE: Our purpose was to emphasize a previously unidentified aspect of cutaneous NLE: the presence of angiomatous or matlike telangiectases in sites without antecedent or concurrent dermatitis.
METHODS: We describe seven patients in which telangiectatic macules or angiomatous papules were primary or early features of NLE.
RESULTS: Five infants lacked a history of preceding or concurrent inflammatory lesions at sites of telangiectasia development. In four infants findings included vulvar or inguinal angiomatous papules.
CONCLUSION: Telangiectases may be a presenting feature of NLE, can be found in sun-protected sites, and may occur independent of "lupus dermatitis
Neonatal lupus erythematosus: an unusual congenital presentation with cutaneous atrophy, erosions, alopecia, and pancytopenia.
Crowley E, Frieden IJ.
University of Illinois, College of Medicine, Urbana, USA
Pediatr Dermatol 1998 Jan-Feb;15(1):38-42 Abstract quote
Neonatal lupus erythematosus (NLE) is a rare disorder believed to be caused by the transplacental passage of specific autoantibodies from the mother to the fetus. Affected infants typically present with either characteristic skin lesions developing in the first month or later in life or congenital heart block.
We report a very unusual case of NLE that was characterized by congenital skin atrophy, erosions, alopecia, and profound pancytopenia. Ro, La, and RNP antibodies were absent, and the diagnosis was made because of light microscopic and immunofluorescent findings.
This case emphasizes that NLE can have widespread congenital skin involvement and suggests that at least some cases are mediated by antibodies other than Ro, La, and RNP.
The health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block.
Lawrence S, Luy L, Laxer R, Krafchik B, Silverman E.
Division of Rheumatology, the Hospital for Sick Children, Toronto, Ontario, Canada.
Am J Med 2000 Jun 15;108(9):705-9 Abstract quote
PURPOSE: Neonatal lupus erythematosus is caused by the transplacental passage of maternal autoantibodies. The aim of this study was to determine the risk of connective tissue disorders in mothers of children with cutaneous neonatal lupus erythematosus, as compared with the risk in mothers of children with congenital heart block, which is also often caused by maternal autoantibodies.
SUBJECTS AND METHODS: We prospectively studied all mothers of children with cutaneous neonatal lupus erythematosus during a 14-year period at the Hospital for Sick Children, Toronto, Ontario, Canada. We identified 28 mothers, of whom 24 were eligible for study. The health and antibody status of the mothers were determined at the birth of the child and at followup.
RESULTS: All mothers had anti-Ro antibodies at the time of birth. Initially 10 mothers were healthy and 14 mothers had either a defined (n = 9) or an undifferentiated (n = 5) autoimmune disorder. At a mean follow-up of 7 years, 13 (1 of whom had died) had a defined connective tissue disease, and 5 had an undifferentiated autoimmune disorder. Only 6 (25%) remained asymptomatic. By comparison, 36 (56%) of 64 mothers of children with congenital heart block were asymptomatic at follow-up (P <0.005).
CONCLUSIONS: The majority of mothers of children with cutaneous neonatal lupus erythematosus had a defined or undifferentiated autoimmune disorder at the time of the child's birth, and others developed these conditions during follow-up. The health of these mothers appears to differ from that of mothers of children with congenital heart block.
PAPULAR AND NODULAR MUCINOSIS
Papular and nodular mucinosis as a presenting sign of progressive systemic sclerosis
JoEllen Van Zander, MD
James C. Shaw, MD
J Am Acad Dermatol 2002;46:304-6 Abstract quote
Papular and nodular mucinosis is a distinct form of cutaneous mucinosis associated with systemic lupus erythematosis.
We report a case in which papular and nodular mucinosis predated early findings of progressive systemic sclerosis.
PARVOVIRUS B19-INDUCED Parvovirus B19-induced systemic connective diseases including LE
Lab Invest 2000;80:61A
Hum Pathol 2000;31:488
Pronounced lymphohistiocytopathy in LE cases
Lymphocytic vasculitis with prominent interface dermatitis in B19 induced dermatomyositis
Parvovirus B19-induced systemic connective diseases including LE
Lab Invest 2000;80:61A
Hum Pathol 2000;31:488
Selective immune defect with an atopic diathesis with parvovirus genome in affected tissue and seropositivity
ROWELL'S SYNDROME Textbook of Dermatology 5th Ed. 1992;2163.
Co-existence of SLE and erythema multiforme
Rowell's syndrome: report of a case.
Fitzgerald EA, Purcell SM, Kantor GR, Goldman HM.
Department of Internal Medicine, Abington Memorial Hospital, Pennsylvania, USA
J Am Acad Dermatol 1996 Nov;35(5 Pt 2):801-3 Abstract quote
A 47-year-old woman presented with a long-standing history of an erythema multiforme-like eruption in association with lupus erythematosus. Unusual laboratory and immunologic findings were consistent with a diagnosis of Rowell's syndrome, which includes lupus erythematosus in association with erythema multiforme-like skin lesions, a speckled antinuclear antibody pattern, and a positive rheumatoid factor.
We believe that our patient meets the criteria for this rarely reported entity.
Child FJ, Kapur N, Creamer D, Kobza Black A.
St. John's Institute. of Dermatology, St. Thomas' Hospital, London, UK.
Clin Exp Dermatol 1999 Mar;24(2):74-7 Abstract quote
Rowell's syndrome is the name given to a distinct group of patients with lupus erythematosus who develop erythema multiforme-like lesions and have a characteristic serological picture.
We report a case of a 29-year-old woman of Afro-Caribbean origin who presented with an erythema multiforme-like eruption on the hands. Subsequently she developed painful erythematous swellings on the feet and scaly plaques on the forearm and thigh consistent with subacute cutaneous lupus. She developed a positive antinuclear factor and had positive anti-Ro and anti-La antibodies and a positive rheumatoid factor.
All of these features are consistent with Rowell's syndrome which we believe is a rare but distinct variant of cutaneous lupus erythematosus.
Redefining Rowell's syndrome.
Zeitouni NC, Funaro D, Cloutier RA, Gagne E, Claveau J.
Centre Hospitalier Universitaire de Quebec, Service de Dermatologie, Pavillon-Hotel-Dieu de Quebec, Canada.
Br J Dermatol 2000 Feb;142(2):343-6 Abstract quote
Rowell's syndrome is believed to be a distinct and rare clinical entity originally described as lupus erythematosus associated with erythema multiforme-like lesions with immunological findings of speckled antinuclear antibodies, anti-La antibodies and a positive test for rheumatoid factor.
We report two additional patients with Rowell's syndrome and review all the diagnostic criteria found in the literature. In view of the inconsistent findings of some of the diagnostic features, we propose that major and minor criteria be used to diagnose Rowell's syndrome.
Widespread photodistibuted but superficial nonscarring lesions on the skin
Annular, papulosquamous, polycyclic eruption
As lesions become confluent, a reticulated appearance may occur
Rarely targetoid appearance
Photoprovocation of skin lesions more common than SLE or DLE
Uncommon in head and neck area
Mild systemic disease
Strong association with autoAb Ro/SS-A and SS-B in 50-60%
Prominent suprbasilar exocytosis of lymphocytes
Alternating interface change with cell poor vacuolar foci alternating with zones of lichenoid dermatitis
Dyskeratosis extending into upper spinous layers
Prominent epidermal atrophy
May have parakeratosis and areas of granular cell diminution
Follicular plugging or basement membrane zone thickening minimal or absent
Mild to moderate mononuclear cell infiltrate confined to the superficial dermis
May have mesenchymal mucin
Must distinguish from other cases of lichenoid connective tissue diseases including:
Anti-Ro associated SLE
Mixed connective disease
N Engl J Med 1995;33:1429
Hum Pathol 1997;28:67
In the elderly, this disease is frequently triggered by drug therapy, mainly thiazides and calcium channel blockers
Uncommon skin presentations include:
Widespread pruritic plaques
Diffuse non-scarring alopecia
Terbinafine-induced subacute cutaneous lupus erythematosus
Gisela Bonsmann, etal.
J Am Acad Dermatol 2001;44:925-31 Abstract quote
Background: Recently, the induction of subacute cutaneous lupus erythematosus (SCLE) and exacerbation of systemic lupus erythematosus by terbinafine have been reported.
Objective: We describe 4 cases of SCLE, one associated with chilblain lupus, which occurred during therapy with oral terbinafine for onychomycosis.
Methods: Of 21 consecutive patients with SCLE attending the outpatient dermatology department at Muenster University clinic during a 1-year period, 4 patients with terbinafine-induced SCLE were seen. Patients were examined fully and photographed; histologic findings as well as serologic and follow-up data were evaluated.
Results: In addition to high titers of antinuclear antibodies (ANA) with a homogeneous pattern, anti-Ro(SS-A) antibodies were present; in 3 of 4 women, anti-La(SS-B) antibodies were also found. All patients had anti-histone antibodies as in drug-induced lupus and showed the characteristic genetic association of SCLE with the HLA-B8,DR3 haplotype; moreover, in 2 cases, HLA-DR2 was also present. After discontinuation of terbinafine, ANA titers decreased; anti-histone antibodies also became undetectable within 4˝ months in 3 patients concomitant with subsidence of the SCLE eruption in all patients.
Conclusion: Terbinafine is a drug that appears to infrequently induce SCLE with high titers of ANAs and anti-histone antibodies in genetically susceptible persons.
Subacute Cutaneous Lupus Erythematosus Induced or Exacerbated by Terbinafine A Report of 5 Cases
Jeffrey P. Callen, MD; Amy P. Hughes, MD; Carol Kulp-Shorten, MD
Arch Dermatol. 2001;137:1196-1198 Abstract quote
Subacute cutaneous lupus erythematosus is a nonscarring, non–atrophy-producing photosensitive cutaneous disorder. Half of the patients have 4 or more of the criteria for classification as systemic lupus erythematosus. In some patients, drugs induce or exacerbate the cutaneous disease.
We describe 5 patients who had either an exacerbation or a new onset of subacute cutaneous lupus erythematosus while taking terbinafine for presumed onychomycosis.
In general, terbinafine is a safe drug, but perhaps patients with known lupus erythematosus or photosensitivity are predisposed to drug-induced or drug-exacerbated disease.
Frequency and severity of systemic disease in patients with subacute cutaneous lupus erythematosus.
Black DR, Hornung CA, Schneider PD, Callen JP.
310 E Broadway, Louisville, KY 40202
Arch Dermatol 2002 Sep;138(9):1175-8 Abstract quote
OBJECTIVE: To compare the frequency and severity of systemic disease in patients with subacute cutaneous lupus erythematosus (SCLE) followed up in a dermatology practice vs patients with systemic lupus erythematosus (SLE) followed up in a rheumatology practice.
DESIGN: Case-control comparison of patients matched for age, sex, and ethnicity.
SETTING: University-affiliated dermatology and rheumatology practices.
PATIENTS: Seventy-six patients with SCLE were compared with 24 patients with SLE.
INTERVENTION: All medical records were reviewed and the patients were interviewed.
MAIN OUTCOME MEASURES: Systemic and serologic findings were compared between patients with SCLE and those with SLE.
RESULTS: Hematologic disorders were present in 6 patients (8%) with SCLE and in 13 patients (54%) with SLE (P<.001). Serositis was present in 1 patient (1%) with SCLE and in 3 patients (12%) with SLE (P =.04). Renal involvement was present in 12 patients (16%) with SCLE and in 6 patients (25%) with SLE (P =.36). Antinuclear antibodies were found in 52 patients (68%) with SCLE compared with 23 patients (96%) with SLE (P =.006). Anti-Ro antibodies were found in 37 patients (49%) with SCLE compared with 10 patients (42%) with SLE (P =.64). Other serologic abnormalities (anti-native DNA, anti-Sm antibody, or anti-U(1)RNP) were present in 6 patients (8%) with SCLE compared with 15 patients (62%) with SLE (P<.001). Photosensitivity was present in 65 patients (86%) with SCLE, compared with 11 patients (46%) with SLE (P<.001).
CONCLUSIONS: This analysis reveals a dissimilar frequency of internal organ involvement between patients with SCLE and SLE. Renal disease was similar in frequency and severity, and documented central nervous system involvement was rare in both groups.
Pauci-inflammatory interface dermatitis
Slight to absent epidermal atrophy
Patchy parakeratosis, may be normal
Basement membrane zone of normal thickness
No follicular plugging
Prominent papillary dermal edema and reticular dermal mucin accumulation-on H and E, present as basophilic beaded globules and strings between and adherent to the collagen bundles
Erythrocyte extravasation, telangiectasia, and basement membrane zone reduplication around blood vessels and at the dermoepidermal junction
Rounded histiocytes containing engulfed nuclear debris, usually close to the dermoepidermal junction, closely resembling an LE cell
Eosinophils are rare to absent and if present, should raise the suspicion of a drug-induced LE
Br J Dermatol 1993;128:332
J Am Acad Dermatol 1989;21:745
J Am Acad Dermatol 1986;15:369
Typically occurs in patients with one or more features of SLE preceding the eurption by months to years
Bullae on diffuse erythema or urticarial base or grouped lesions
Generalized but preferentially involves the trunk and flexural surfaces
Diagnosis must be established by:
Diagnosis of SLE by ACR criteria
Widespread, nonscarring, vesiculobullous eruption
Subepidermal blisters with dermal inflammation characterized by neutrophilic papillary microabsesses similar to dermatitis herpetiformis
DIF demonstration of linear or granular IgG and/or IgM in lesional and nonlesional skin
Most patients have antigenicity to noncollagenous domain of type VII collagen but other basement membrane components may be involved
Neutrophilic interface dermatitis often associated with effacement of the retia, morphology reminiscent of linear IgA disease
Histiocytes engulfing nuclear debris of disintegrating neutrophils
Tissue eosinophilia may be present but not as prominent as bullous pemphigoid
Concomittant mesenchymal mucinosis
DIF continuous band of IgG along DE junction
Homogeneous with superimposed granular band, wider than the thin band of BP or EBA
Codominant expression of IgA and IgM
Salt-split skin localizes to floor
Immunogold localizes to sublamina densa region
J Am Acad Dermatol 1999;41:250
Am J Dermatopathol 1999;21:356
This is a variant of DLE presenting with brawny indurated plaques
Tends to involve the neck, trunk, and upper extremities, sometimes in an annular configuration
Marked mesenchymal mucin deposition
Usually pauci-cellular inflammatory cell infiltrate but occasionally pronounced
Tend to resolve completely with local therapy in the absence of either scarring or atrophy
Eur J Dermatol 2000;10:184
Associated with X-linked granulomatous disease
Histopathologic findings in lupus erythematosus tumidus: Review of 80 patients.
Kuhn A, Sonntag M, Ruzicka T, Lehmann P, Megahed M.
Departments of Dermatology at Heinrich-Heine-University of Dusseldorf and University of Witten-Herdecke.
J Am Acad Dermatol. 2003 Jun;48(6):901-8. Abstract quote
BACKGROUND: In a recent study, we demonstrated that lupus erythematosus (LE) tumidus (LET) is a distinct subset of cutaneous LE (CLE), which is clinically characterized by erythematous, urticaria-like, nonscarring plaques in sun-exposed areas.
OBJECTIVE: Our purpose was to analyze skin biopsy specimens from 80 patients with this disease and to determine whether it could be differentiated from other variants of CLE on histopathologic grounds.
METHODS: Skin biopsy specimens from 53 primary and 38 UVA- and/or UVB-induced lesions of 80 patients with LET were examined and compared with skin biopsy specimens from patients with discoid LE (DLE) and subacute CLE (SCLE).
RESULTS: Specimens from LET lesions showed a characteristic and diagnostic pattern of perivascular and periadnexal cellular infiltrates in the papillary and reticular dermis composed almost entirely of lymphocytes. In some cases, few scattered neutrophils were present. Furthermore, interstitial mucin deposition was observed in all specimens, as confirmed by colloidal iron staining. In contrast to discoid LE and subacute CLE lesions, epidermal atrophy or alteration at the dermoepidermal junction was not detected.
CONCLUSION: Skin lesions of patients with LET present with specific histopathologic features, and the differences compared with subacute CLE and discoid LE further support the concept to consider LET as a separate entity of CLE.
Lupus erythematosus tumidus--a neglected subset of cutaneous Lupus erythematosus: report of 40 cases.
Kuhn A, Richter-Hintz D, Oslislo C, Ruzicka T, Megahed M, Lehmann P.
Department of Dermatology, Heinrich-Heine-University, Dusseldorf, GErmany.
Arch Dermatol 2000 Aug;136(8):1033-41 Abstract quote
BACKGROUND: Lupus erythematosus tumidus (LET) is characterized clinically by erythematous, succulent, edematous, nonscarring plaques in sun-exposed areas. Results of histological examination show perivascular and periadnexal lymphocytic infiltration and interstitial mucin deposition. The main differential diagnoses are polymorphous light eruption, Jessner's lymphocytic infiltration of the skin, reticular erythematous mucinosis, and pseudolymphoma. Since its first description in 1930, LET has been documented rarely in the literature, and its clinical importance has not been fully appreciated.
OBSERVATIONS: We characterized 40 patients with clinical and histological features of LET observed at our department from 1984 through 1998. The onset of the disease clustered in summer because of sun exposure, and 28 (70%) of the patients showed a remarkable photosensitivity confirmed by results of provocative phototesting. A complete resolution of the skin lesions was seen after systemic therapy with antimalarials and, in some cases, with local corticosteroids or spontaneously without any treatment. In 4 (10%) of the patients, antinuclear antibodies were detected; however, there was no evidence of underlying systemic involvement in any of the patients.
CONCLUSIONS: Our data constitute the largest number of patients with LET collected until now. The clinical picture, extreme photosensitivity, histological findings, and effective treatment with antimalarials are so characteristic that LET should be considered as a separate entity and differentiated from other variants of cutaneous LE.
Phototesting in lupus erythematosus tumidus--review of 60 patients.
Kuhn A, Sonntag M, Richter-Hintz D, Oslislo C, Megahed M, Ruzicka T, Lehmann P.
Department of Dermatology, Heinrich-Heine-University, Dusseldorf, Germany.
Photochem Photobiol 2001 May;73(5):532-6 Abstract quote
Photosensitivity is an important characteristic feature of several forms of lupus erythematosus (LE), and induction of skin lesions by UV-A and UV-B irradiation has been proved to be an optimal model for evaluating light sensitivity in patients with this disease. Because lupus erythematosus tumidus (LET) has rarely been documented in the literature and is often difficult to differentiate from other photodermatoses such as polymorphous light eruption, we performed photoprovocation tests in 60 patients with LET according to a standardized protocol.
Areas of uninvolved skin on the upper back were irradiated with single doses of UV-A (100 J/cm2) and/or UV-B (1.5 minimal erythema dose) daily for three consecutive days. Interestingly, patients with LET are more photosensitive than those with subacute cutaneous lupus erythematosus, and in our study experimental phototesting revealed characteristic skin lesions in 43 patients (72%). Because of the latency period in developing positive phototest reactions, it might be difficult for these patients to link sun exposure with their skin lesions. Furthermore, our data revealed a positive correlation of antinuclear antibodies and positive provocative phototest reactions in these patients as seen for other forms of LE.
In conclusion, the high incidence of positive phototest reactions in correlation with the clinical findings, history of photosensitivity and antinuclear antibodies enable the classification of LET as the most photosensitive type of LE.
Flame Figures in Urticarial Lesions Accompanying Systemic Lupus Erythematosus
Joerg Wenzel; Ingrid Boehm, M.D.; Rainer Gerdsen, M.D.; Thomas Bieber, M.D., Ph.D.; Manfred Uerlich, M.D.
From the Department of Dermatology, University of Bonn, Germany.
Am J Dermatopathol 2001;23:533-535 Abstract quote
We present the case of a 38-year-old female patient with systemic lupus erythematosus and atypical urticarial skin lesions with an alteration in shape, but not complete disappearance, within 24 hours. Hematoxylin-eosin–stained sections revealed flame figures.
We review urticarial lesions in lupus erythematosus and discuss the possible pathomechanisms.
Vascular lesions are usually confined to patients with SLE
All sizes and types of vessels and all organs can be affected
Immune mediated deposits and thrombotic lesions secondary to hyperviscosity and hypercoagulable states may occur
Cohort of 667 SLE patients found:
Vasculitis 36% (61% of these had a single episode)
Vasculitis in skin alone in 82%
Visceral organs alone 12.4%
Skin and viscera in 5%
Leukocytoclastic vasculitis Most common vasculitic lesion
May be confined to skin but also may be present in the lungs and glomeruli
J Cutan Pathol 1998;25:215
Sterile neutrophilic folliculitis with perifollicular vasculopathy
May represent cases of SLE as well as other connective tissue disorders
J Am Acad Dermatol 1992;26:441
Erythrocyte extravasation, slight leukocytoclasia, and neutrophilic infiltration of vessel walls with minimal fibrin deposition
Extracutaneous manifestations include:
Hypocomplementemia is best predictor of systemic sequela
Lymphocytic vasculitis May be associated with cryofibrinogenemia and/or lupus anticoagulant Livedoid vasculopathy
Netlike pattern of bluish discoloration of skin, often localized to an extremity
Thrombosis usually only visible in smal and intermediate sized vessels in the subcutis or deep reticular dermis-superficial dermal vessels usually only show compensatory ectasia
In biopsies of patients with hemorrhage and ulcerating livedo, there are bland luminal thrombi occluding deep dermal vessels with necrosis of the epidermis and dermis
EXTRACUTANEOUS ORGANS See file KIDNEY
World Health Organization (WHO) Classification of Lupus Nephritis
The kidney is involved in 60-70% of cases by routine light microscopy but in nearly all cases if examined with electron microscopy or immunofluorescence
Damage begins with deposition of DNA-anti-DNA complexes within the glomeruli basement membrane
Immunoglobulins and complement are then attracted leading to cellular damage.
These deposits may occur in the mesangium, intramembranous, subepithelial, or subendothelial
Subendothelial deposits may cause thickening of the wall leading to a wire loop lesion
In about 50% of patients, the kidney tubules may also have deposits along the basement membrane.
Nonlupus nephritides in patients with systemic lupus erythematosus: A comprehensive clinicopathologic study and review of the literature
Elzbieta Baranowska-Daca, MD, PhD
Yeong-Jin Choi, MD, PhD
Roberto Barrios, MD, etal.
Hum Pathol 2001;32:1125-1135. Abstract quote
Renal biopsy specimens from patients with systemic lupus erythematosus (SLE) rarely show changes that are pathogenetically and morphologically unrelated to SLE. The morphology and behavior of these nonlupus nephritides are not well known.
Two hundred fifty-two renal biopsies performed on 224 patients with SLE collected from 3,036 native kidney biopsies performed between 1975 and 1998 were reviewed, and those that showed nonlupus nephritides (index biopsies) were selected for studies.
Thirteen biopsy specimens with nonlupus nephritides were identified in 13 patients, who belonged to 3 clinically distinct groups.
Group I included 6 patients in whom SLE was diagnosed at the time of index biopsies. The index biopsies in these patients showed focal segmental glomerusclerosis (FSGS; 3 cases), Immunoglobulin (Ig) M nephropathy (1 case), and thin basement membrane disease (1 case). The diagnostic features for FSGS included segmental sclerosis involving at least 1 glomerulus, absence of lupus nephritis or other conditions that may cause nonspecific segmental sclerosis of glomeruli such as ischemia or nephrosclerosis, and nephrotic-range proteinuria. There was uniform, global, diffuse and marked thinning of the glomerular basement membrane in the case of thin basement membrane disease.
Group II included 3 patients in whom SLE was diagnosed 2 to 9 years before the time of index biopsies and SLE was active at the time of biopsy. The index biopsies in these patients showed FSGS (2 cases) and hypertensive nephrosclerosis (1 case).
Group III included 4 patients in whom SLE was diagnosed 5 to 36 years before the time of index biopsies and SLE was inactive at the time of biopsy. The index biopsies in these patients showed 1 case each of amyloidosis, FSGS, hypertensive nephrosclerosis, and allergic acute tubulointerstitial nephritis. Previous renal biopsies, performed in 5 patients, showed IgM nephropathy (1 case), diffuse proliferative lupus GN (1 case), focal proliferative lupus GN (1 case), and mesangial proliferative lupus GN (2 cases). Follow-up biopsies, performed in 3 patients, confirmed the diagnosis of FSGS (2 cases) and hypertensive nephrosclerosis (1 case) noted in the index biopsies. Nonlupus nephritides may occasionally be encountered in SLE patients, regardless of clinical or serologic disease activity.
These renal lesions display a broad morphologic spectrum in which FSGS seems most frequent. Renal biopsy plays a crucial role in identifying these lesions, which may have prognostic and therapeutic implications distinct from those of lupus nephritis.
Class Classification Description I Normal by light, electron, and immunofluorescent microscopy II Mesangial lupus glomerulonephritis 20%
III Focal proliferative glomerulonephritis 20% IV Diffuse proliferative glomerulonephritis 40-50%
Most serious lesion
V Membranous glomerulonephritis 15%
LIVER Acute vasculitis
Within the portal triads
Alveolar Hemorrhage and Renal Microangiopathy in Systemic Lupus Erythematosus Immune Complex Small Vascular Injury With Apoptosis
Michael D. Hughson, etal.
Arch Pathol Lab Med 2001;125:475–483 Abstract quote
Context.—Acute alveolar hemorrhage in systemic lupus erythematosus usually occurs as a pulmonary-renal syndrome. In most cases, the lungs show “bland” alveolar hemorrhage with little or no inflammation. Whether this alveolar injury is similar to the better-defined noninflammatory renal lupus vasculopathy is unresolved.
Objectives.—To investigate the relationships and the mechanisms of small vascular injury in the lung and kidney of 2 lupus patients who died of diffuse AH. Methods.—We investigated the relationship of AH to immune complex deposition in the lungs of 6 patients with systemic lupus erythematosus and correlated the findings with glomerular and vascular disease in the kidney. Lung and kidney were studied by light, immunofluorescence, and/or electron microscopy; apoptosis was investigated using in situ nick-end labeling.
Results.—The clinical course of 2 patients was complicated by alveolar hemorrhage, and the lungs of these patients revealed alveolar wall immune complex deposits and bland alveolar hemorrhage. These 2 patients had World Health Organization class IV lupus nephritis and renal arterioles involved by a noninflammatory lupus vasculopathy. Apoptosis was identified in the lupus microangiopathy and in alveolar walls within areas of alveolar hemorrhage. Alveolar wall immune complex deposits were not found in 4 patients who had a lupus glomerulonephritis but did not have renal lupus vasculopathy. Apoptosis was not seen in renal arterioles or lungs of these 4 cases, except in areas of diffuse alveolar damage or herpesvirus pneumonia.
Conclusions.—Our findings indicate that alveolar hemorrhage in systemic lupus erythematosus, characterized by bland alveolar wall changes, is pathogenetically similar to the lupus microangiopathy of the kidney. In both lung and kidney, the pathogenesis of the microvascular injury appears to be related to immune complex deposition and the induction of apoptosis.
LYMPH NODES Follicular hyperplasia with plasma cells
Chronic B cell stimulation
SPLEEN Enlargement with capsular thickening
Follicular hyperplasia with plasma cells
Onion-skinning of penicilliary arteries with thickening and fibrosis
CHARACTERIZATION Special stains Direct immunofluorescence (DIF) See file Indirect immunofluorescence (IIF) See file
DIFFERENTIAL DIAGNOSIS OF MAJOR SUBTYPES OF LUPUS ERYTHEMATOSUS
(Modified from J Cutan Pathol 2001;28:1-23.)
FEATURE SLE SCLE DLE Skin Lesions Scale Fine, easily detached Fine, easily detached Thick, adherent Follicular atrophy Absent Absent Present Photodistribution Present Marked Present Scarring Absent Absent Present Atrophy Usually absent Usually absent Present-often marked Pigmentary alteration Slight Slight Often marked Telangiectasia Present Present Present >/= 4 ARA criteria for SLE (incidence) 100% 40% 10% Positive Lupus Band Test Lesional skin >90% 60% 90% Non-lesional sun-protected skin Active disease 90%
Inactive disease 30%
ADDITIONAL DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES INTERFERON INJECTION SITE
- Lupus-like reaction to interferon at the injection site: report of five cases.
Department of Dermatology, University Hospital, Madrid, Spain.
- J Cutan Pathol. 2007 Dec;34 Suppl 1:18-21. Abstract quote
Background: Interferon therapy at the injection sites has been related to different cutaneous lesions including erythema and induration as the most frequent ones. While the glycoprotein induces fatigue, fever and is even believed to precipitate autoimmune disorders such as type I diabetes, thyroid disease and systemic lupus erythematosus, a lupus erythematosus-like histologic reaction at the interferon injection site has never been reported. To our knowledge, a microscopic self-resolving lesion mimicking lupus erythematosus at the injection site of interferon has not been described.
Results: We report five cases of cutaneous lesions at the inoculation site of interferon with a histopathologic lupus erythematosus-like pattern. Three of them were receiving interferon alfa therapy because of a malignant melanoma and the other two patients were receiving interferon beta-1b for multiple sclerosis. Biopsy specimens taken from different lesions showed similar microscopic findings consisting of dermal mucin deposits and dense lymphocytic infiltrates along hair follicles with hydropic degeneration of follicular basal layer.
Conclusions: Multiple cutaneous lesions related to interferon at the injection site have been reported, but none of them with a histologic lupus-like presentation. In this study we describe five cases in which interferon therapy has induced a resolutive cutaneous lesion mimicking lupus erythematous. This peculiar microscopic pattern has been previously described once before, but interpreted as cutaneous mucinosis.
Lupus profundus, indeterminate lymphocytic lobular panniculitis and subcutaneous T-cell lymphoma: a spectrum of subcuticular T-cell lymphoid dyscrasia.
Magro CM, Crowson AN, Kovatich AJ, Burns F.
Ohio State University Medical Center, Columbus, Ohio, USA.
J Cutan Pathol 2001 May;28(5):235-47 Abstract quote
INTRODUCTION: The diagnosis and classification of lymphocytic lobular panniculitis (LLP) has historically proven to be a difficult challenge. We encountered 32 cases of primary LLP which could be categorized as: 1) lupus erythematosus profundus (LEP) (19 patients); 2) an indeterminate group termed indeterminate lymphocytic lobular panniculitis (ILLP) (6 patients); and 3) subcutaneous T-cell lymphoma (SCTCL) (7 patients).
OBJECTIVE: We attempted to better define the subtypes of LLP by morphologic, phenotypic and genotypic features and to correlate those features to clinical presentation and outcome.
METHOD: Skin biopsy material was studied by conventional light microscopy, through immunophenotyping performed on sections from paraffin-embedded, formalin-fixed tissue and in some cases on sections of tissue frozen after receipt in physiological (Michel's) medium, and by polymerase chain reaction single-stranded conformational polymorphism analysis to assess for clonality of T-lymphocytes. Clinical features were correlated to histologic, phenotypic, and genotypic analyses.
RESULTS: Patients with LEP had a prior diagnosis of LE or overlying skin changes which light microscopically were characteristic of LE. Patients with ILLP had no concurrent or prior history of LE, no systemic symptoms or cytopenias, and a clinical course not suggestive of lymphoma. Cases of SCTCL showed hemophagocytic syndrome and/or lesional progression with demise attributable to the disease. Lesions in all groups showed proximal extremity predilection. Females predominated in the LEP group. The average age of onset was 38, 40 and 55 years in the LEP, ILLP and SCTCL groups, respectively. Cytopenia was seen in 4 LEP patients; 1 also developed fever. In LEP and ILLP, lesions resolved with hydroxychloroquine and/or steroid therapy, with recurrences following cessation of therapy. In the SCTCL group 4 developed hemophagocytic syndrome, 4 died within 2 years of diagnosis, and 3 went into remission following chemotherapy. The LEP and SCTCL groups manifested histological similarities: dense perieccrine and lobular lymphocytic infiltration, lymphoid atypia, histiocytes with ingested debris, eosinophilic necrosis of the fat lobule and thrombosis. The atypical lymphocytes although pleomorphic did not have a cerebriform morphology. The infiltrate in ILLP had a similar cytomorphology and distribution with variable angioinvasion which in all save one case was of lesser intensity and was not associated with significant fat necrosis or vasculitis. Germinal centers, dermal/subcuticular mucin deposition and an atrophying interface dermatitis with hyperkeratosis and follicular plugging were largely confined to the LEP group. Erythrophagocytosis, characteristic of SCTCL, usually indicated a supervening subcuticular lymphoid dyscrasia when encountered in ILLP and LEP. SCTCL showed a selective loss of CD5 expression with or without diminution in CD7 and monoclonal CD3 expression. Of 4 cases studied, 3 showed a CD8 dominant infiltrate while 2 others exhibited CD56 and CD30 positivity, respectively. All cases of SCTCL with amplifiable DNA showed T-cell clonality. Similar molecular and phenotypic features indicative of subcuticular lymphoid dyscrasia were encountered in cases of LEP and ILLP including a reduction in CD5, CD7, and/or monoclonal CD3 expression, a preponderance of CD8 lymphocytes within the subcutaneous fat and T-cell clonality. These cases showed lymphoid atypia with variable erythrophagocytosis. Cases of phenotypically abnormal and/or clonal LEP showed one or more of local destruction, lesional size progression, fever, and cytopenias, but lesions responded to hydroxychloroquine and/or prednisone therapy and death attributable to panniculitis could not be documented. Cases that were phenotypically normal and without clonality had none of the aforesaid atypical clinical features.
CONCLUSION: Lymphoid atypia, erythrophagocytosis, loss of certain pan T-cell markers, a reduced CD4/8 ratio and TCR rearrangement define subcuticular T-cell lymphoid dyscrasia, including a subset of LEP and ILLP. The subcuticular lymphoid infiltrates represent a spectrum of histologic, immunophenotypic, and molecular abnormalities which range from those which are clearly benign to those which are clearly neoplastic, and also encompasses those cases which defy precise classification into the two aforesaid poles.
- J Cutan Pathol. 2006 Nov;33(11):721-725 Abstract quote
- Background: Rare cases of a non-bullous neutrophilic dermatosis occurring in patients with lupus erythematosus (LE) have been reported, often as the presenting manifestation of the disease.
Methods: We reviewed hematoxylin and eosin-stained slides and obtained clinical information from four additional patients, two of whom had no prior history of LE.
Results: All patients were female, aged 16-59 (mean age 37). Clinically, the skin lesions were characterized by widely distributed pruritic papules and plaques. Three patients presented with systemic symptoms, including fever, arthritis and malaise. Histopathologic examination in all cases showed a superficial perivascular and interstitial neutrophilic infiltrate with leukocytoclasis. There was no evidence of vasculitis. Mild focal vacuolar change was a subtle feature seen only in the biopsies of the two patients with a prior history of LE.
Conclusions: It is important to consider LE in the differential diagnosis of non-bullous neutrophilic dermatoses.
DLE VERSUS SCLE
\Subacute cutaneous lupus erythematosus and discoid lupus erythematosus. Comparative histopathologic findings.
Bangert JL, Freeman RG, Sontheimer RD, Gilliam JN.
Arch Dermatol 1984 Mar;120(3):332-7 Abstract quote
Subacute cutaneous lupus erythematosus (SCLE) is a recently described distinct subset of lupus erythematosus (LE) having characteristic clinical, serologic, and genetic findings.
This study describes the histopathologic characteristics of SCLE and determines whether it could be differentiated from discoid lupus erythematosus (DLE) on histopathologic grounds alone. Biopsy specimens from 33 patients having either SCLE or DLE, as defined by strict clinical criteria, were examined without knowledge of the clinical diagnosis. Histologic discrimination between SCLE and DLE was accomplished in 82%. The specimens from DLE lesions had substantially more hyperkeratosis, basement membrane thickening, follicular plugging, and superficial and deep inflammatory cell infiltrate, while SCLE had more epidermal atrophy.
The histopathologic differences between SCLE and DLE further support the concept that SCLE is distinct from DLE and should be considered a unique subset of LE.
SLE VERSUS SCLE
Subacute cutaneous lupus erythematosus versus systemic lupus erythematosus: diagnostic criteria and therapeutic implications.
Chlebus E, Wolska H, Blaszczyk M, Jablonska S.
Department of Dermatology, Warsaw School of Medicine, Warszawa, Poland.
J Am Acad Dermatol 1998 Mar;38(3):405-12 Abstract quote
BACKGROUND: The nosologic position of subacute cutaneous lupus erythematosus (SCLE) is controversial. More than four American Rheumatism Association (ARA) criteria for systemic lupus erythematosus (SLE) are found in a proportion of patients diagnosed as having SCLE; thus such cases could be classified as SLE.
OBJECTIVE: Our purpose was to determine whether ARA criteria for SLE are helpful in differentiating SCLE from SLE and whether cutaneous and visceral changes, immunologic findings, and photosensitivity provide a basis for diagnosis of SCLE.
METHODS: A cohort of 143 patients (79 with SCLE, 58 with SLE, and six with overlapping features of SCLE and SLE) was studied clinically, histologically, and immunologically as well as by phototesting. The patients were observed for up to 10 years, and the course of the disease and response to therapy were evaluated in each group.
RESULTS: SCLE differed from SLE by cutaneous changes, significantly less frequent kidney involvement, serositis and arthritis, and the rare presence of double-stranded DNA, U1RNP, and Sm antibodies characteristic of SLE. Ro(SS-A) and La(SS-B) antibodies were detected with similar frequency, and photosensitivity was not related to the presence of Ro antibody. In contrast, photoreproduction (appearance of LE lesion in irradiated area) was significantly more frequent in patients with SCLE. The course of SCLE in older patients was less severe than in younger patients, and aggressive therapy was usually not required.
CONCLUSION: Patients with SCLE (although the majority fulfill more than four ARA criteria for SLE) show significant differences from those with SLE in terms of cutaneous and visceral involvement, immunologic findings, photosensitivity, course of the disease, and the requirement for therapy. Therefore SCLE should be recognized as a separate subset. However, cases of overlapping SLE and SCLE suggest a close relation.
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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008
J Cutan Pathol 2001;28:1-23.
Anti-Phospholipid Antibody and the Lupus Anticoagulant
Autoimmune and Anti-nuclear antibodies (ANA)
Skin Immunofluorescence (Lupus Band Test)
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