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This rare blistering disorder combines features of erythema multiforme and pemphigus. Currently, this disease is also known as Paraneoplastic Autoimmune Multiorgan Syndrome (PAMS). It has been associated with numerous internal malignancies, usually lymphomas, but also thymomas and Castleman's disease. Rarely it has followed systemic interferon therapy or radiation therapy. It is characterized by mucosal erosions and bullous skin eruptions resembling pemphigus. The key to the diagnosis rests with the pathologist who can identify some characteristic features presented in the outline below.

A recent study of 22 patients has identified one clinical and two biological features which have both high sensitivity (82-86%) and high specificity (83-100%) for the diagnosis. These features are:

Association with a lymphoproliferative disorder
Indirect immunofluorescence (IIF) labelling of rat bladder
Recognition of the envoplakin and/or periplakin bands in immunoblotting


Disease Associations  
Laboratory/Radiologic/Other Diagnostic Testing  
Gross Appearance and Clinical Variants  
Histopathological Features and Variants  
Special Stains/
Electron Microscopy
Differential Diagnosis  
Commonly Used Terms  
Internet Links  

SYNONYMS Paraneoplastic autoimmune multiorgan syndrome
AGE Usually adults
Paraneoplastic autoimmune multiorgan syndrome (paraneoplastic pemphigus) in a child: case report and review of the literature.

Lane JE, Woody C, Davis LS, Guill MF, Jerath RS.

Section of Dermatology, Department of Medicine, Medical College of Georgia, 1004 Chafee Ave, Augusta, GA 30912, USA.
Pediatrics. 2004 Oct;114(4):e513-6. Abstract quote  

Paraneoplastic autoimmune multiorgan syndrome, also known as paraneoplastic pemphigus, has been observed only rarely among children.

We describe a 10-year-old boy with typical clinical and histologic findings of paraneoplastic pemphigus associated with Castleman's disease. His disease was refractory to resection of the tumor and aggressive combination immunosuppressive therapies. The patient died 1 year after presentation, as a result of complications of bronchiolitis obliterans.

This case is unusual because of the young age of the patient.

Paraneoplastic pemphigus associated with Castleman tumor: a commonly reported subtype of paraneoplastic pemphigus in China.

Wang J, Zhu X, Li R, Tu P, Wang R, Zhang L, Li T, Chen X, Wang A, Yang S, Wu Y, Yang H, Ji S.

Department of Dermatology, Peking University First Hospital, Beijing, China.

Arch Dermatol. 2005 Oct;141(10):1285-93. Abstract quote  

BACKGROUND: Castleman tumor, a rare lymphoproliferative disorder, is one of the associated tumors in paraneoplastic pemphigus. We analyzed the characteristics of a group of patients with Castleman tumor to clearly understand and to improve the prognosis of the disease.

OBSERVATIONS: Ten cases of paraneoplastic pemphigus associated with Castleman tumor treated in the Department of Dermatology, Peking University First Hospital, Beijing, China, from May 1, 1999, to March 31, 2004, were analyzed for clinical aspects, characteristics and histologic features of the tumors, and computed tomographic findings. Literature was reviewed and data were compared with our cases. Castleman tumor was a frequently reported neoplasm in association with paraneoplastic pemphigus in China. The disease was found to be caused by an autoimmune reaction originating from the B lymphocytes in the Castleman tumor.

CONCLUSIONS: Castleman tumor in association with paraneoplastic pemphigus is a commonly reported subtype of paraneoplastic pemphigus in China. Early detection and removal of the Castleman tumor are crucial for the treatment of this tumor-associated autoimmune disease.
Paraneoplastic syndrome and intrathoracic Castleman disease.

Hung IJ, Lin JJ, Yang CP, Hsueh C.

Department of Medicine, Division of Hematology/Oncology, Chang Gung Children's Hospital, Chang Gung University, Taoyuan, Taiwan.

Pediatr Blood Cancer. 2005 Jul 26; [Epub ahead of print] Abstract quote  

We report two cases of intrathoracic Castleman disease presenting with paraneoplastic syndrome. Patient 1 was a 10-year-old girl with short stature. She was found to have delayed bone age, slow growth velocity, and iron-deficiency anemia, which was refractory to treatment. Thrombocytosis and hypergammaglobulinemia were later detected. Chest X-ray revealed a hilar mass.

Patient 2 was a 14-year-old boy who had severe cough, progressive mucocutaneous erosion, and dermatitis. Chest X-ray showed a mediastinal mass. Sections of skin biopsy showed findings consistent with pemphigus disease.

In each case, the histological diagnosis of Castleman disease was made.
Castleman's tumours and production of autoantibody in paraneoplastic pemphigus.

Wang L, Bu D, Yang Y, Chen X, Zhu X.

Department of Dermatology, Peking University First Hospital, Beijing, China.
Lancet. 2004 Feb 14;363(9408):525-31. Abstract quote  

BACKGROUND: Paraneoplastic pemphigus is an autoimmune mucocutaneous disease associated with Castleman's tumours, which when surgically removed often result in great improvement of mucocutaneous lesions. An IgG autoantibody against epidermal proteins is often used as a diagnostic marker for disease. Our aim was to ascertain the role of Castleman's tumours in production of the autoantibody and pathogenesis of paraneoplastic pemphigus.

METHODS: We enrolled seven patients with paraneoplastic pemphigus associated with Castleman's disease and assessed the effect of removal of tumours on mucocutaneous lesions in six individuals and on autoantibody titre with indirect immunofluorescence in four patients. We cultured tumour cells from one patient and assayed the secreted autoantibody. Finally, we characterised the gene sequence and expression of the variable region of the immunoglobulin heavy chain (IgV(H)) in tumour B cells from all patients by reverse transcription-PCR, DNA sequencing, and in-situ hybridisation.

FINDINGS: Cutaneous lesions disappeared within 6-11 weeks after resection of tumours. Mucosal lesions also improved in this period, but lasted for 5-10 months overall. Autoantibody titre decreased and became undetectable within 5-9 weeks in three of four patients assessed. We identified secreted autoantibody, similar to that identified in patients' serum, in cultured tumour cells. The tumour B-cells of the seven patients shared and expressed two rearrangement patterns of complementarity determining region 3 (CDR3) of IgV(H).

INTERPRETATION: Secreted autoantibody from Castleman's tumours, which reacts against epidermal proteins, could be an essential factor in the pathogenesis of paraneoplastic pemphigus. We noted clonal rearrangement, resulting in similar variable regions of IgV(H), in tumour B cells isolated from all seven patients. However, whether this pattern is associated with autoimmunity remains to be ascertained.

Paraneoplastic pemphigus in association with Castleman's disease.

Nikolskaia OV, Nousari CH, Anhalt GJ.

Department of Dermatology, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross Building, Suite 771, Baltimore, MD 21205, U.S.A.
Br J Dermatol. 2003 Dec;149(6):1143-51. Abstract quote  

BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with lymphoproliferative neoplasms, and frequently with a very rare tumour, Castleman's disease.

OBJECTIVES: To analyse the clinical history, immunopathological and histopathological findings in 28 patients with a confirmed diagnosis of PNP and Castleman's disease.

METHODS: Sera from all patients were assayed by indirect immunofluorescence (IF) and immunoprecipitation (IP) for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay for detection of desmoglein (Dsg)1 and Dsg3 autoantibodies.

RESULTS: Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions were seen in 19 of 28. Twenty cases of Castleman's disease were of the hyaline vascular type, four were of plasmacytoid type and four were of mixed type. Striking findings included pulmonary destruction leading to bronchiolitis obliterans in 26 patients and fatal outcome due to respiratory failure in 22 patients with pulmonary involvement. Histological findings included lichenoid and interface dermatitis with variable intraepithelial acantholysis. Direct IF showed deposition of IgG and C3 in the mouth and skin in 24 of 28 patients. However, indirect IF detected serum IgG autoantibodies in all patients. IP revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 19 patients. Dsg3 and Dsg1 autoantibodies were present in 22 and 11 patients, respectively, and plectin autoantibodies in 23 patients.

CONCLUSIONS: PNP in association with Castleman's disease presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins are the most diagnostic markers. Pulmonary injury with respiratory failure is the cause of death in most cases.

Paraneoplastic pemphigus in association with a retroperitoneal Castleman's disease presenting with a lichen planus pemphigoides-like eruption. A case report and review of literature.

Hsiao CJ, Hsu MM, Lee JY, Chen WC, Hsieh WC.

Department of Dermatology, National Cheng-Kung University Hospital, 138 Sheng-Li Road, Tainan, Taiwan 704.

Br J Dermatol 2001 Feb;144(2):372-6 Abstract quote

A 50-year-old man presented with severe mucosal erosions of the lips, oral cavity and perianal area, a lichen planus-like eruption on the trunk and extremities and scaly plaques of the palms and soles. The clinical impression was of Stevens--Johnson syndrome, or paraneoplastic pemphigus (PNP). Histopathology revealed vacuolar interface and lichenoid dermatitis with dyskeratosis and suprabasal acantholytic vesiculation. Direct immunofluorescence showed deposition of IgG in the intercellular space and linear deposition of C3 along the basal membrane zone. Indirect immunofluorescence revealed circulating IgG with intercellular staining of the epithelium of rat urinary bladder. Western blotting demonstrated bands of 250- and 230-kDa antigens.

The clinical, histological and immunological features were consistent with the lichen planus pemphigoides variant of PNP. A retroperitoneal hyaline-vascular Castleman's disease was detected and excised. The skin lesions worsened initially after tumour resection but improved gradually, leaving extensive melanosis after cyclosporin and mycophenolate mofetil treatment.

Paraneoplastic pemphigus associated with non-Hodgkin B-cell lymphoma and good response to prednisone.

Martinez De Pablo MI, Iranzo P, Mascaro JM, Llambrich A, Baradad M, Herrero C.

Servicio de Dermatologia, Hospital Clinic, C/Villaroel 170, ES-08036 Barcelona, Spain.

Acta Derm Venereol. 2005;85(3):233-5. Abstract quote  

Paraneoplastic pemphigus is a life-threatening autoimmune bullous disease associated with neoplasia, generally of lymphoid origin.

Immunosuppressive therapy is often disappointing and there are only a few reports of patients surviving more than 2 years. These cases were generally associated with benign neoplasms.

We report here the case of a patient with paraneoplastic pemphigus associated with non-Hodgkin B-cell lymphoma who had a surprisingly good response to systemic corticosteroids and remains free of lesions more than 3 years later despite progression of her neoplasm.


AUTOANTIBODIES J Clin Invest. 1998;102:775-782.
J Am Acad Dermatol. 1995;32:441-447.
Desmoplakin I
250 kd
Bullous pemphigoid antigen
230 kd
Desmoplakin II
210 kd
190 kd protein
190 kd
170 kd protein
170 kd

Conformational epitope mapping and IgG subclass distribution of desmoglein 3 in paraneoplastic pemphigus.

Futei Y, Amagai M, Hashimoto T, Nishikawa T.

Department of Dermatology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
J Am Acad Dermatol. 2003 Dec;49(6):1023-8. Abstract quote  

BACKGROUND: Pemphigus vulgaris (PV) shows autoimmune reaction against desmoglein 3 (Dsg3), whereas paraneoplastic pemphigus (PNP) shows autoimmune reaction against Dsg3 as well as numerous members of the plakin family. It has been demonstrated that in PV, dominant epitopes reside in N-terminal adhesive regions of Dsg3 and that the dominant IgG subclass against Dsg3 is IgG4.

OBJECTIVE: We attempted to map conformational epitopes and analyze IgG subclass distribution against Dsg3 in PNP. METHOD: Epitopes on Dsg3 for circulating IgG autoantibodies from PNP (n = 22) were studied with competition enzyme-linked immunosorbent assay (ELISA) using domain-swapped molecules between Dsg3 and Dsg1 and were compared with those for IgG autoantibodies from PV (n = 22). IgG subclass distribution was analyzed with PNP serum by Dsg3 ELISA (n = 17).

RESULTS: Epitopes on Dsg3 in PNP were distributed more broadly through the extracellular domain of Dsg3 than were those in PV, although the N-terminal extracellular domains of Dsg3 were more frequently recognized than the C-terminal extracellular domains. IgG subclass in PNP was IgG1 and IgG2 dominant.

CONCLUSION: Autoimmune response against Dsg3 in PNP is more diversified than that in PV, a finding that suggests PNP and PV have different pathophysiologic mechanisms for triggering production of anti-Dsg3 IgG.

Clinical phenotype and anti-desmoglein autoantibody profile in paraneoplastic pemphigus

Manabu Ohyama, etal.

J Am Acad Dermatol 2001;44:593-8 Abstract quote

Background: Paraneoplastic pemphigus (PNP) has similar features to pemphigus vulgaris (PV), including circulating anti-desmoglein (Dsg) IgG as pathogenic autoantibodies. When PV is divided into mucosal dominant type and mucocutaneous type, mucosal dominant type has only anti-Dsg3 IgG, whereas the mucocutaneous type has both anti-Dsg3 and anti-Dsg1 IgG.

Objective: The purpose of this study was to determine whether there is a difference in anti-Dsg autoantibody profile between mucosal dominant PNP and mucocutaneous PNP.

Methods: Twenty-one patients with PNP were categorized as mucosal dominant and mucocutaneous types based on clinical information. Antibody titers against Dsg3 and Dsg1 were measured by enzyme-linked immunosorbent assay by means of recombinant Dsg1 and Dsg3.

Results: There were 9 cases of mucosal dominant type and 12 cases of mucocutaneous type. Eight of 9 cases of mucosal dominant type were positive for anti-Dsg3 IgG, but 3 of them were also positive for anti-Dsg1 IgG. All 12 cases of mucocutaneous type were positive for anti-Dsg3 IgG, whereas only 6 of them were positive for anti-Dsg1 IgG.

Conclusion: There was no clear association between the clinical phenotype and anti-Dsg antibody profile in PNP as seen in PV. This finding suggests that besides anti-Dsg IgG other pathologic mechanisms such as lichenoid reaction or interface dermatitis may be involved in the blister formation in PNP.


Classification, Clinical Manifestations, and Immunopathological Mechanisms of the Epithelial Variant of Paraneoplastic Autoimmune Multiorgan Syndrome:
A Reappraisal of Paraneoplastic Pemphigus

Arch Dermatol. 2001;137:193-206

The disease may display a spectrum of at least 5 different clinical and immunopathological mucocutaneous variants:
Erythema multiforme–like
Graft-vs-host disease–like
Lichen planus–like

Authors suggest that the more encompassing term "paraneoplastic autoimmune multiorgan syndrome," or PAMS, be applied

The pathophysiological mechanisms of PAMS involve both humoral and cellular autoimmunity responses:
Epithelial cell membrane antigens other than DSG1 or DSG3 are targeted by effectors of PAMS autoimmunity

In addition to the known "PNP antigenic complex," epithelial targets recognized by PNP antibodies included:
240-, 150-, 130-, 95-, 80-, 70-, 66-, and 40/42-kd proteins but excluded DSG1 and DSG3

In addition to skin and the epithelium lining upper digestive and respiratory tract mucosa, deposits of autoantibodies were found in kidney, urinary bladder, and smooth as well as striated muscle

Autoreactive cellular cytotoxicity was mediated by:
CD8+ cytotoxic T lymphocytes, CD56+ natural killer cells, and CD68+ monocytes/macrophages

Inducible nitric oxide synthase was visualized both in activated effectors of cellular cytotoxicity and their targets

Keratin 14–positive basal epithelial cells sloughed from the large airways and obstructed small airways.

Apoptosis of damaged basal cells mediates epithelial clefting, and respiratory failure results possibly from obstruction of small airways with sloughed epithelial cells



Suprabasilar acantholysis, keratinocytic necrosis, and vacuolar interface dermatitis

Lymphocytes with occasional eosinophils and neutrophils are present


Direct immunofluorescence (DIF) Direct immunofluorescence shows intercellular and basement membrane staining for C3 and IgG
Paraneoplastic pemphigus with negative direct immunofluorescence in epidermis or mucosa but positive findings in adnexal structures.

Department of Dermatology, Hospital Sta. Creu i St. Pau, Barcelona, Spain.

J Cutan Pathol. 2009 Jan;36(1):34-8. Abstract quote

INTRODUCTION: Paraneoplastic pemphigus (PNP) is considered an autoimmune, multiorgan disease caused by antiplakin antibodies. We present three PNP patients who had negative epithelial direct immunofluorescence (DIF) findings in one or more biopsies.

PATIENTS: An early lip biopsy of uninvolved oral epithelia in patient 1 was negative. A later biopsy from foreskin showed intense intercellular immunoglobulin G (IgG) deposits in the epithelia. In the early phase of the disease in patient 2, the intercellular fluorescence was negative in the epidermis, while intercellular IgG and C3 were observed in the sweat ducts. A later biopsy showed weak intercellular epidermal IgG and C3 fluorescence. Patient 3 showed intercellular IgG and/or C3 in follicular, sebaceous and sweat duct structures in several biopsies. No intercellular IgG or C3 was observed in the epithelia.

DISCUSSION: The presence of immunoreactants in adnexal structures suggests that desmoplakins can be more strongly expressed in adnexa than in the epidermis, facilitating visualization of antibody deposits.

CONCLUSIONS: Negative DIF findings in epithelia do not rule out the diagnosis of PNP, and the presence of IgG and/or C3 at the intercellular level of adnexal structures can help establish this diagnosis.
Indirect immunofluorescence (IIF)

Antiepidermal antibodies recognizing both the epithelial surface of keratinocytes and the basement membrane zone

Labels substrates such as rat urinary bladder, myocardium, and liver

Immunoblot analysis Circulating antibodies against 190kd band of periplakin and 210kd band of envoplakin

A nonfatal case and 2 fatal cases of paraneoplastic pemphigus: can a complement indirect immunofluorescent test help to identify fatal "group A" paraneoplastic pemphigus cases?

Beutner EH, Pelton S, Hashimoto T, Xu Y, Plunkett RW, Korman NJ, Helm TN, Jablonska S.

Department of Microbiology, University at Buffalo, State University of New York, USA.

J Am Acad Dermatol 2002 Dec;47(6):841-51 Abstract quote

We studied 3 recent cases of paraneoplastic pemphigus (PNP) in detail. Two patients died despite concerted management efforts. One patient received no treatment after the appearance of PNP and recovered completely from both PNP and lymphoma.

Multiple serum studies of these 3 patients plus 9 other proven PNP cases revealed that 8 of 9 fatal PNP cases (referred to here as "group A") had distinctive cell surface antibodies detected by complement indirect immunofluorescent (CIIF) tests on monkey esophagus sections.

By contrast, none of the sera from 3 patients with PNP who experienced long-term survival (referred to here as "group B") and none of 20 pemphigus vulgaris or 10 pemphigus foliaceus control sera revealed similar beaded cell surface CIIF reaction patterns, a difference that is statistically significant (P <.0001). Cell surface CIIF reaction patterns of group A PNP antibodies resemble the pattern of pemphigus antibody reactions in indirect immunofluorescent tests on the same substrate; however, the latter tend to be thinner and more linear, whereas the cell surface CIIF pattern tends to be more beaded, suggesting possible desmosomal reactions.

We believe this test is useful in identifying an aggressive group A form of PNP.

A monoclonal antibody against the paraneoplastic pemphigus (PNP) antigen, envoplakin: cDNA sequences encoding the variable regions of heavy and light chains.

Ahn JH, Lee MG, Kim SC, Lee TH.

Department of Biology, Yonsei University College of Science, Seoul 120-749, Korea.

Mol Cells. 2004 Oct 31;18(2):237-41. Abstract quote  

Paraneoplastic pemphigus (PNP) is an acquired autoimmune disorder characterized by severe mucosal erosion, and polymorphous cutaneous lesions associated with neoplasia. PNP patients have circulating autoantibodies that bind to stratified and nonstratified epithelia. Previously, we showed that envoplakin was a component of the antigen complex recognized by PNP sera.

In the present study we generated a monoclonal antibody, EVP-YS, against human envoplakin. The antibody bound to keratinocyte cell surfaces and reacted with the 210-kDa PNP antigen, confirming its specificity for envoplakin. The variable regions of the heavy (H) and light (L) chain genes were cloned from the hybridoma and shown to belong to mouse H chain subgroup III and kappa light chain subgroup V, respectively. The L chain of EVP-YS was 98% identical to the k chains of some autoantibodies and anti-nucleic acid antibodies, and had an identical amino acid sequence in all three complementary determining regions, suggesting that the H chains determine the specificity of the EVP-YS-envoplakin interaction.

The EVP-YS antibody can be used to evaluate the sensitivity and specificity of clinical, histological, and immunological criteria for diagnosing PNP.

Paraneoplastic pemphigus with clinical features of lichen planus associated with low-grade B cell lymphoma.

Coelho S, Reis JP, Tellechea O, Figueiredo A, Black M.

Department of Dermatology, University Hospital, P. 3000-075 Coimbra, Portugal.
Int J Dermatol. 2005 May;44(5):366-71. Abstract quote  

BACKGROUND: Neoplasia-induced lichen planus is described as a cell-mediated reaction to unknown epithelial antigens. Paraneoplastic pemphigus (PNP), characterized by the presence of a specific array of autoantibodies, probably represents a different form of presentation of the same autoimmune syndrome where the mucocutaneous expression depends on the dominant pathologic mechanism.

METHODS: The authors report a case of PNP with predominant lichen planus-like lesions and review the relevant literature. We observed a 74-year-old female with vesico-bullous, erosive, target-shaped and flat papular lichenoid lesions on the lower legs, palms and soles, evolving for 3 weeks. Histopathology revealed a lichenoid dermatitis. Direct immunofluorescence showed C3 deposition around keratinocytes and epidermal IgG intranuclear deposition. Indirect immunofluorescence revealed circulating IgG with intercellular staining on rat bladder substrate. Immunoblotting demonstrated bands of 130, 190, 210 and 250 kDa antigens. A pararenal B cell lymphoma was found.

RESULTS: Oral corticotherapy with 40 mg prednisolone daily was initiated with a good cutaneous response. Four months later, cyclophosphamide (50 mg/day) was introduced because of a discrete enlargement of the pararenal mass. The patient died on the seventh month of follow up as a result of respiratory insufficiency.

CONCLUSION: PNP has different forms of presentation and the lack of a consensus about diagnostic criteria may contribute to underdiagnosed cases. Advances on the knowledge of the sensitivity and specificity of diagnostic criteria have allowed a better accuracy of diagnosis.

PROGNOSIS Dependent upon the underlying malignancy
Exacerbation of paraneoplastic pemphigus by cyclophosphamide treatment: detection of novel autoantigens and bronchial autoantibodies.

Preisz K, Horvath A, Sardy M, Somlai B, Harsing J, Amagai M, Hashimoto T, Nagata Y, Fekete S, Karpati S.

Department of Dermatology, Keio University School of Medicine, Tokyo, Japan.
Br J Dermatol. 2004 May;150(5):1018-24. Abstract quote  

A 48-year-old woman with a follicular, grade III, B-cell non-Hodgkin lymphoma developed clinical, immunopathological and histological features of paraneoplastic pemphigus. The skin symptoms flared after repeated cyclophosphamide infusions, and were preceded and accompanied by a progressive dyspnoea. Although the skin and oral mucosal disease went into remission with high-dose steroid and intravenous immunoglobulin therapy, the severe alveolitis led to death.

Immunoblotting of human epidermal extracts showed that the patient's serum IgG reacted with the 210-kDa envoplakin, 190-kDa periplakin, as well as the recombinant protein of BP180 NC16a domain. IgG and IgA enzyme-linked immunosorbent assays for desmoglein 3 were positive, too. Indirect immunofluorescence studies on COS-7 cells transiently transfected with desmocollin 1-3 cDNAs showed that the patient's serum contained IgG and IgA antibodies to desmocollin 3 as well as IgG antibodies to desmocollin 2. Serum IgG and IgA strongly stained rat bronchial epithelium, corresponding to autoantibodies possibly involved in the pathomechanism of the severe lung disease.

In this case, which was characterized by a mixed IgA/IgG antibody panel displaying known and unique antigenicity, the serious episodes of paraneoplastic pemphigus flared after cyclophosphamide treatment.
Paraneoplastic pemphigus secondary to fludarabine evolving into unusual oral pemphigus vegetans.

Powell AM, Albert S, Oyama N, Sakuma-Oyama Y, Bhogal B, Black MM.

Immunofluorescence Department, St John's Institute of Dermatology, St Thomas' Hospital, Lambeth Palace Road, London SE1 7EH, UK.
J Eur Acad Dermatol Venereol. 2004 May;18(3):360-4. Abstract quote  

We report a patient with chronic lymphocytic leukaemia who developed paraneoplastic pemphigus (PNP) soon after the initiation of fludarabine therapy.

He presented with severe oral and cutaneous erosions. Initially, he had high titres of circulating autoantibodies as detected by indirect immunofluorescence (IF) on multiple epithelial substrates (normal human skin, monkey oesophagus, and rat bladder) and by desmoglein 1 and 3 enzyme-linked immunosorbent assays (ELISAs).

His oral erosions have subsequently progressed into unusual hyperplastic papillomatous lesions affecting the inner aspect of lips and buccal mucosae, histologically consistent with pemphigus vegetans. Desmoglein 1 antibodies and IF on rat bladder substrate have become negative after 18 months of therapy.

Several agents had been initiated to bring the disease under control originally, but a partial remission was achieved and maintained with mycophenolate mofetil and low-dose prednisolone.
TREATMENT Dependent upon the underlying malignancy
Alemtuzumab-induced remission of both severe paraneoplastic pemphigus and leukaemic bone marrow infiltration in a case of treatment-resistant B-cell chronic lymphocytic leukaemia.

Hohwy T, Bang K, Steiniche T, Peterslund NA, d'Amore F.

Department of Dermatology, Aarhus University Hospital, Denmark.
Eur J Haematol. 2004 Sep;73(3):206-9. Abstract quote  

BACKGROUND: Alemtuzumab (MabCampath; ILEX Pharmaceuticals, Geneva, Switzerland) is a humanised monoclonal antibody directed against CD52. It belongs to a new group of monoclonal antibodies with anti-neoplastic effects used in chronic lymphocytic leukaemia (CLL) either as first-line treatment or in those cases resistant to alkylating drugs. Paraneoplastic pemphigus (PNP) is a severe mucocutaneus disease mostly associated with B-cell lymphoproliferative disorders. Independent of the course of the underlying malignancy, this disease is often resistant to conventional immunosuppressive treatment and may lead to death as a result of infectious complications.

CASE PRESENTATION: We report a case where an ongoing long-term remission of PNP has been induced by alemtuzumab in a patient with an underlying B-CLL. A 68-yr-old male with a 4-yr history of B-CLL presented with a widespread blistering eruption on the extremities and trunk and a severe stomatitis. The diagnosis of PNP relied on the clinical, histological and direct immunofluorescence findings. Despite intensive treatment strategies with various immunosuppressive drugs and antibiotics, blisters continued to develop and the patient was deteriorating. When treated with alemtuzumab the mucocutaneous lesions healed almost completely within a few weeks and the patients' general condition improved significantly. After 12 wk of treatment with alemtuzumab, the CLL infiltration of the bone marrow previously quantified at 75-80% remitted completely. Twelve months later, the patient was still in remission with only a small residual ulceration on the lip and one on the penis.

CONCLUSIONS: Based on this case report we recommend treatment with alemtuzumab to severe cases of PNP in CLL. However, further follow-up of this case is needed in order to assess the long-term effect of alemtuzumab treatment in PNP.
Using rituximab (anti-CD20 antibody) in a patient with paraneoplastic pemphigus.

Schadlow MB, Anhalt GJ, Sinha AA.

Department of Dermatology, New York Weill Cornell Medical College, New York Presbyterian Hospital, New York, New York, USA.
J Drugs Dermatol. 2003 Oct;2(5):564-7. Abstract quote  

Paraneoplastic pemphaigus (PNP) is a rare autoimmune mucocutaneous blistering disease that is commonly associated with underlying B-cell neoplasms. There is no standard therapy for PNP. Potent immunosuppression has been the only potentially effective treatment in the setting of malignancy because there is no correlation between tumor burden and activity of disease.

Two recent case reports have noted the resolution of lesions of PNP after treatment of the underlying CD20+ B-cell lymphomas with rituximab. Rituximab is an anti-CD20 antibody that has had some success in treating proliferative B-cell disorders.

We report a case of PNP in the setting of B-cell lymphoma that did not respond to this novel therapy, and discuss rituximab's putative mechanism of action along with the clinical settings in which this novel therapy may prove useful in the treatment of PNP.

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