Interstitial granulomatous dermatitis with arthritis is a rare disorder with cutaneous and joint manifestations first described in 1993. The pathognomonic sign of this eruption is the rope sign, a linear prominent cutaneous bands in the axillae that are associated with arthritis.
Disease Associations Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Differential Diagnosis Commonly Used Terms
DISEASE ASSOCIATIONS CHARACTERIZATION COCCIDIODOMYCOSIS
Interstitial granulomatous dermatitis associated with pulmonary coccidioidomycosis
David J. DiCaudo, MD
Suzanne M. Connolly, MD
J Am Acad Dermatol 2001;45:840-5 Abstract quote
Background: Coccidioides immitis is a soil-dwelling fungus found in arid regions of the Western Hemisphere. Interstitial granulomatous dermatitis is a histopathologic pattern that may be a reactive manifestation of diverse systemic diseases.
Objective: Our purpose was to describe clinical and histopathologic findings in 5 patients who presented with interstitial granulomatous dermatitis associated with pulmonary coccidioidomycosis.
Methods: Medical records and skin biopsy slides from 5 patients were retrospectively reviewed. Results: In each patient, edematous papules, nodules, and plaques developed abruptly during the onset of an acute febrile illness. Coccidioidomycosis was confirmed by serology. Skin biopsy specimens revealed interstitial granulomatous dermatitis with neutrophils, leukocytoclasis, and eosinophils. Fungal stains (5/5 cases) and fungal cultures (2/2 cases) revealed no organisms within the skin biopsy specimens.
Conclusion: Interstitial granulomatous dermatitis may be a presenting feature of pulmonary coccidioidomycosis and may possibly represent a reactive manifestation of the infection.
CHARACTERIZATION RADIOLOGIC LABORATORY MARKERS AUTOANTIBODIES
Interstitial granulomatous dermatitis with cutaneous cords and arthritis: A disorder associated with autoantibodies
Laurence Verneuil, MD, etal.
J Am Acad Dermatol 2001;45:286-91 Abstract quote
Interstitial granulomatous dermatitis with arthritis is a new entity characterized by linear or arciform subcutaneous cords.
We describe a patient presenting with typical cutaneous lesions extending from the anterior and posterior part of the axillae to the flank. The lesions had been present for 6 years with flares and remission. Histopathologic examination revealed a bandlike infiltrate of histiocytes in the reticular dermis with focal areas of palisading around necrotic collagen bundles. A few atypical histiocytes were also present. As previously described, it was associated with serologic findings of an autoimmune disease, especially high titers of anti-DNA antibodies.
The possible inclusion of the interstitial granulomatous dermatitis in the continuous spectrum of the palisaded neutrophilic and granulomatous dermatitis of immune complex disease is also discussed.
Interstitial granulomatous dermatitis with arthritis.
Long D, Thiboutot DM, Majeski JT, Vasily DB, Helm KF.
Department of Medicine/Division of Dermatology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey 17033, USA.
Am Acad Dermatol 1996 Jun;34(6):957-61 Abstract quote
BACKGROUND: Interstitial granulomatous dermatitis with arthritis is an uncommon systemic disorder involving the cutaneous and musculoskeletal systems. The eruption may mimic other dermatoses including granuloma annulare, erythema chronicum migrans, and the inflammatory stage of morphea. Key histopathologic characteristics, along with clinical correlation, allow accurate diagnosis.
OBJECTIVE: We describe the clinical, serologic, and histologic features in three patients with interstitial granulomatous dermatitis with arthritis.
METHODS: Skin biopsy specimens were examined and correlated with the clinical and laboratory findings.
RESULTS: Erythematous, annular, indurated plaques on the extremities were present in two women. An erythematous, papular eruption on the head and neck was present in a third patient. All patients had myalgia and migratory polyarthralgias of the extremities along with various serologic abnormalities. Histologic examination revealed a dense lymphohistiocytic interstitial infiltrate involving primarily the reticular dermis. Foci of necrobiotic collagen were present. Vasculitis was absent.
CONCLUSION: Interstitial granulomatous dermatitis with arthritis is unique multisystem disease with variable cutaneous expression. Abnormal serologic findings indicate a possible connection to collagen vascular disease.
Interstitial granulomatous dermatitis with plaques.
Tomasini C, Pippione M.
Department of Medical and Surgical Specialties, Second Dermatologic Clinic, University of Turin.
J Am Acad Dermatol 2002 Jun;46(6):892-9 Abstract quote
BACKGROUND: Interstitial granulomatous dermatitis is a histopathologic pattern with variable clinical appearance associated with autoimmune systemic diseases. The frequency of its different cutaneous expressions and its association with autoimmune diseases are not known.
OBJECTIVE: We describe the clinical, serologic, and histologic features in 17 patients with interstitial granulomatous dermatitis with a clinical presentation consisting of large erythematous plaques.
METHOD: Skin biopsy specimens fulfilling criteria for diagnosis of interstitial granulomatous dermatitis were selected and correlated with the clinical and laboratory findings.
RESULTS: The study included 1 man and 16 women with multiple, asymptomatic, round to oval, erythematous plaques, most often on folds of the skin, in a bilateral and somewhat symmetric distribution. Most of patients had rheumatoid polyarthralgias along with various serologic abnormalities, often connected to collagen vascular diseases. Histologic examination disclosed a distinctive interstitial granulomatous dermatitis characterized by a diffuse infiltration of the interstitium by histiocytes with piecemeal fragmentation of collagen and formation of small granulomas around degenerative areas in concert with variable numbers of polymorphonuclear leukocytes sprinkled within the infiltrate. Churg-Strauss granulomas in miniature and flame figures were occasionally observed and indicated continued or increased activity of the associated autoimmune disease(s).
CONCLUSIONS: Interstitial granulomatous dermatitis with plaques is a distinct entity with highly reproducible clinical and histopathologic features; recognition of these features identifies a patient who may have an underlying systemic autoimmune disorder.
HISTOLOGICAL TYPES CHARACTERIZATION General Collagen degeneration associated with a dermal bandlike infiltrate composed mainly of histiocytes. VARIANTS PLAQUES
Interstitial granulomatous dermatitis with plaques.
Aloi F, Tomasini C, Pippione M.
Department of Dermatology, University of Turin, Italy.
Am J Dermatopathol 1999 Aug;21(4):320-3 Abstract quote
We report on the clinical and histopathologic findings of four patients who had asymptomatic, erythematous to violaceous plaques symmetrically distributed on the upper aspect of the thighs, lateral chest, and in two cases also on the abdomen and flexor surface of the elbows.
All of the patients were women; two of them had arthritis, which in one case was associated with an autoimmune disorder, and another had autoimmune thyroiditis. Histopathologically, all cases showed similar changes consisting of an interstitial granulomatous dermatitis involving mostly the lower reticular dermis. Histiocytes were the predominant cellular component, arranged interstitially and in small palisades around foci of degenerated collagen bundles in concert with large numbers of neutrophils and eosinophils.
Interstitial granulomatous dermatitis can present different clinical expressions, including linear cords, papules, and, as in our cases, plaques. This peculiar histopathologic pattern falls into the spectrum of cutaneous extravascular necrotizing granuloma, a condition that is often associated with systemic autoimmune disease.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES DRUG ERUPTION
The interstitial granulomatous drug reaction: a distinctive clinical and pathological entity.
Magro CM, Crowson AN, Schapiro BL.
Department of Pathology, Beth Israel Deaconess Centre, Harvard Medical School, Pathology Services, Inc., Cambridge, Massachusetts, USA.
J Cutan Pathol 1998 Feb;25(2):72-8 Abstract quote
We present 20 patients in whom drug therapy was associated with interstitial histiocytic infiltrates with variable degeneration of collagen and elastic fibers mimicking early lesions of granuloma annulare (GA).
Most patients had a reproducible clinical presentation comprising erythematous-to-violaceous, nonpruritic plaques, often with an annular pattern, predominantly involving inner aspects of the arms, medial thighs and intertriginous areas. The most frequent clinical differential diagnoses included cutaneous T cell lymphoma, erythema annulare centrifigum (EAC), GA, and lupus erythematosus. A drug reaction was suspected in only 3 cases.
The implicated drug classes included calcium channel blockers, angiotensin converting enzyme inhibitors, beta-blockers, lipid-lowering agents, antihistamines, anticonvulsants and antidepressants. Patients were often on two or more of these drugs; all have been associated with pseudolymphomatous infiltrates of the skin, the presumptive basis of which is iatrogenic pertubation of immune function.
The defining histomorphology was diffuse infiltration of the interstitium by lymphocytes and histiocytes with piecemeal fragmentation of collagen and elastic fibers in concert with a vacuolar interface dermatitis. Ten cases showed intermediate and transformed lymphocytes with hyperchromatic convoluted nuclei disposed interstitially within the dermis or along the dermoepiderma junction with variable epidermotropism. In the 15 patients who discontinued the implicated drug, lesional resolution occurred.
We propose the designations interstitial granulomatous drug reaction for this novel cutaneous reaction pattern.
Interstitial granulomatous drug reaction with a histological pattern of interstitial granulomatous dermatitis.
Perrin C, Lacour JP, Castanet J, Michiels JF.
Department of Pathology, University of Nice, France.
Am J Dermatopathol 2001 Aug;23(4):295-8 Abstract quote
The interstitial granulomatous drug reaction (IGDR) is a novel drug-associated entity, characterized by violaceous plaques with a predilection for skin fold areas. Light microscopically, it resembles the incipient diffuse interstitial phase of granuloma annulare. Differentiating light microscopic features include the absence of complete collagen necrobiosis, the presence of interface dermatitis, and variable lymphoid atypia.
The lack of vasculitis rules out the extravascular necrotizing granuloma (Winkelmann granuloma) associated with systemic disease. The differential diagnosis with interstitial granulomatous dermatitis with arthritis as defined by Ackerman et al. has not been studied until now. Our aim was to determine the histologic criteria allowing us to differentiate IGDR without interface dermatitis and lymphoid atypia from interstitial granulomatous dermatitis.
We report three patients with IGDR triggered, in two cases by respectively angiotensin convertin enzyme (ACE) inhibitors and furosemide, and in one case by the association of an ACE inhibitor, furosemide, and fluindione.
Histologic examination showed a histological pattern of interstitial granulomatous dermatitis. We found a dense, diffuse histiocytic infiltrate distributed interstitially and in palisaded array within the reticular dermis. Eosinophils and some neutrophils were scattered throughout the infiltrate. In some tiny foci, enveloped by histiocytes, thick collagen bundles associated with basophilic nuclear debris or "flame figures" were seen. Vasculitis, interface dermatitis, or lymphoid atypia were absent.
Our study allowed us to expand the histological spectrum of IGDR including a histological pattern similar to interstitial granulomatous dermatitis. The lack of degenerated collagen could be a subtle clue in favor of interstitial granulomatous dermatitis triggered by a drug.
Lichenoid and granulomatous dermatitis.
Magro CM, Crowson AN.
Department of Pathology, Cell Biology, and Anatomy, Medical College of Thomas Jefferson University, Philadelphia, PA, USA.
Int J Dermatol 2000 Feb;39(2):126-33 Abstract quote
BACKGROUND: The prototypic lichenoid eruptions, lichen planus (LP), lichenoid drug eruptions, secondary syphilis, and collagen vascular disease, are defined histologically by a band-like lymphocytic infiltrate in close apposition to the epidermis. We describe a novel form of lichenoid dermatitis with a granulomatous component.
DESIGN: Skin biopsies from 40 patients demonstrating a band-like lymphocytic infiltrate with concomitant granulomatous inflammation were encountered over 4 years. Clinicians were contacted to elucidate underlying triggers and medical illnesses.
RESULTS: A lichenoid dermatitis, a linear eruption, vasculitis, annular erythema, and erythroderma were among the clinical presentations. A drug-based etiology was implicated in 14 cases: the drugs included antibiotics, lipid-lowering agents, anti-inflammatory drugs, antihistamines, hydroxychloroquine sulfate, and angiotensin-converting enzyme inhibitors. Over one-third of patients with drug-related eruptions had other medical illnesses associated with cutaneous granulomatous inflammation, namely rheumatoid arthritis (RA), Crohn's disease, hepatitis C, diabetes mellitus, and thyroiditis. A microbial trigger was implicated in 12 patients in the context of infective id reactions to herpes zoster, Epstein-Barr virus (EBV), or streptococci, or active infections by Mycobacterium tuberculosis, M. leprae, fungi, and spirochetes. The remainder had hepatobiliary disease and RA without obvious exogenous triggers, cutaneous T-cell lymphoma (CTCL), and idiopathic lichenoid eruptions (i.e. LP, lichen nitidus, and lichen striatus). One patient with LP had underlying multicentric reticulohistiocytosis. The histiocytic infiltrate assumed one or more of five light microscopic patterns: (i) superficially disposed loose histiocytic aggregates; (ii) cohesive granulomata within zones of band-like lymphocytic infiltration with or without deeper dermal extension; (iii) a diffuse interstitial pattern; (iv) scattered singly disposed giant cells; and (v) granulomatous vasculitis. Additional features included lymphocytic eccrine hidradenitis in those patients with drug reactions, hepatobiliary disease, and antecedent viral illnesses, tissue eosinophilia and erythrocyte extravasation in drug hypersensitivity, granulomatous vasculitis in patients with microbial triggers, drug hypersensitivity or RA, and lymphoid atypia in lesions of CTCL or drug hypersensitivity.
CONCLUSIONS: The cutaneous lichenoid and granulomatous reaction may reflect hepatobiliary disease, endocrinopathy, RA, Crohn's disease, infection, or a drug reaction. One-fifth of cases represent idiopathic lichenoid disorders. Lymphoproliferative disease or pseudolymphomatous drug reactions must be considered in those cases showing lymphoid atypia.
PALISADED NEUTROPHILIC AND GRANULOMATOUS DERMATITIS
The histopathologic spectrum of palisaded neutrophilic and granulomatous dermatitis in patients with collagen vascular disease.
Chu P, Connolly MK, LeBoit PE.
Department of Dermatology, University of California--San Francisco.
Arch Dermatol 1994 Oct;130(10):1278-83 Abstract quote
BACKGROUND AND DESIGN: Patients with lupus erythematosus, rheumatoid arthritis, and other diseases in which circulating immune complexes occur can develop a papular eruption on the extremities. Terms including Churg-Strauss granuloma, cutaneous extravascular necrotizing granuloma, rheumatoid papules, superficial ulcerating rheumatoid necrobiosis, and interstitial granulomatous dermatitis with arthritis have been given to this entity. We evaluated the clinical and histopathologic features of six patients with systemic lupus erythematosus, two patients with rheumatoid arthritis, and one patient with an incompletely characterized collagen vascular disease who developed cutaneous papules.
RESULTS: The lesions were located largely on the extremities and were symmetrically distributed in most of the patients. They ranged from a few to many and from skin colored to erythematous, and they had smooth, ulcerated, or umbilicated surfaces. Histopathologic examination showed a spectrum of changes that, we believe, reflect the evolution of lesions, ie, leukocytoclastic vasculitis with dense neutrophilic infiltrates and degenerated collagen in early lesions; palisaded granulomas surrounding leukocytoclastic debris, fibrin, and altered collagen in fully developed lesions; and, as the process wanes, palisaded granulomas with dermal fibrosis and scant neutrophilic debris. Each stage of development elicits a different differential diagnosis, which can be resolved by the application of histopathologic criteria.
CONCLUSION: The histopathologic findings are consonant with the evolution of an immune complex-mediated disease. The diverse histopathologic, and sometimes clinical, appearances account for the variety of names given to this condition. We propose the name palisaded neutrophilic and granulomatous dermatitis of immune complex disease to reflect the histopathologic evolution and clinical aspects of this condition.
Weedon D. Weedon's Skin Pathology. Churchill Livingstone. 1997.
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Last Updated 7/1/2002
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