Lichen planus and cicatrizing conjunctivitis: characterization of five cases.

PURPOSE: To report the clinical and immunopathologic features and the response to therapy in a series of six patients with cicatrizing conjunctivitis due to lichen planus. DESIGN: Retrospective case series. METHODS: All six patients were seen in an ocular pemphigoid clinic. Clinical, immunopathologic, and serologic features were evaluated and therapeutic response in each patient was monitored. RESULTS: All six patients had evidence of conjunctival scarring. Five patients had lichen planus of the oral mucosa and gingiva; one patient had involvement of the skin. Histologic findings consisted of thickened epithelium and an interface lymphocytic infiltrate along the lamina propria. In three patients, electron microscopy of the conjunctiva revealed thickening, fragmentation, and duplication of the basement membrane zone. Direct immunofluorescence examination of the conjunctiva and oral mucosa demonstrated linear and shaggy fibrinogen deposition along the basement membrane zone, confirming the diagnosis of lichen planus. All six patients were placed on immunosuppressive therapy with control of the disease. However, only one patient was able to discontinue the anti-inflammatory medication and have the lichen planus remain in remission. CONCLUSIONS: Lichen planus should be included in the differential diagnosis of cicatrizing conjunctivitis. Performing appropriate investigations to distinguish conjunctival lichen planus from other autoimmune diseases such as mucous membrane pemphigoid is critical to managing the patient with cicatrizing conjunctivitis appropriately. Oral cyclosporine effectively controlled the conjunctival lichen planus in four of the six cases.

Treatment of pemphigus vulgaris and pemphigus foliaceus with mycophenolate mofetil.

BACKGROUND: Mycophenolate mofetil is increasingly being used as a corticosteroid-sparing agent in immunosuppressive regimens. OBJECTIVE: To elucidate the effectiveness of mycophenolate as adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. DESIGN: Historical prospective study. SETTING: University hospital. PATIENTS: The study included 42 consecutive patients with pemphigus (31 with pemphigus vulgaris and 11 with pemphigus foliaceus) who had relapses during prednisone taper or had clinically significant adverse effects from previous drug therapy. RESULTS: Remission was achieved in 22 (71%) and 5 (45%) of patients with pemphigus vulgaris and pemphigus foliaceus, respectively. Partial remission was achieved in 1 (3%) and 4 (36%), respectively. The median time to achieve complete remission was 9 months (range, 1-13 months). The treatment was administered for a median of 22 months, and the median follow-up period was 22 months. Seventy-seven percent of patients had no adverse effect. Two patients had side effects severe enough to necessitate discontinuation of treatment, one because of symptomatic but reversible neutropenia and the other because of nausea. CONCLUSION: Mycophenolate is an effective and safe adjuvant in the treatment of both pemphigus vulgaris and pemphigus foliaceus.

Cutaneous polyarteritis nodosa in patients presenting with atrophie blanche.

BACKGROUND: The term 'atrophie blanche' is used both as a descriptive term denoting ivory-white stellate scars on the lower limbs as well as a diagnostic label synonymous with livedoid vasculitis, an ill-defined entity. Medium-sized vasculitides, such as polyarteritis nodosa (PAN), occasionally present with ulceration resulting in ivory-white stellate scarring on the lower limbs and may potentially be misdiagnosed as livedoid vasculitis. OBJECTIVES: To assess the occurrence, clinical and immunopathological features of medium-sized vasculitis in patients presenting with atrophie blanche without clinical and/or compression duplex ultrasonographic evidence of venous insufficiency. METHODS: We retrospectively evaluated patients presenting with atrophie blanche at the Department of Dermatology of Johns Hopkins Medical Institutions, from April 1996 until April 2002, following the diagnostic guidelines for leg ulcers of the Division of Immunodermatology. Deep and multiple skin biopsies were performed for histology. Investigations for underlying vasculitis, thrombophilia, nerve conduction studies and compression duplex ultrasonography of the lower extremities were performed in all patients. RESULTS: Of 29 consecutive patients presenting with atrophie blanche, six had underlying medium-sized vasculitis consistent with PAN, three of whom had previously been diagnosed to have segmental hyalinizing vasculitis/vasculopathy (livedoid vasculitis/vasculopathy) on superficial biopsies. All six patients with cutaneous PAN were women with a median age of 36.5 years (range 34-46) and with a median duration of the disease prior to diagnosis of 18 years (range 3-30). Of the six cutaneous PAN patients, four had neurological involvement evidenced by clinical symptoms and nerve conduction studies. No evidence of any other extracutaneous involvement was found. Erythrocyte sedimentation rate and tests for vasculitis and thrombophilic were normal in all six patients. None had evidence of venous insufficiency. Immunosuppressive therapy was effective in controlling PAN-associated cutaneous and neurological disease. Of the remaining 23 patients, two had antiphospholipid syndrome and one had homocystineaemia; all three also had evidence of venous insufficiency. One patient had multiple myeloma-associated type I cryoglobulinaemia and 19 patients had venous insufficiency alone. None of the non-PAN patients had abnormalities in the nerve conduction studies. CONCLUSIONS: In patients presenting with atrophie blanche without evidence of venous insufficiency and thrombophilia, PAN should be excluded, particularly in the presence of mononeuritis multiplex. Repeated and deep biopsies are often necessary to reveal the accurate underlying pathology of necrotizing medium-sized vasculitis in the reticular dermis and the subcutis, especially in the setting of atrophie blanche lesions. Immunosuppressive therapy was effective in controlling the PAN-associated clinical manifestations.

Infliximab for peristomal pyoderma gangrenosum.

Peristomal pyoderma gangrenosum (PPG) is a variant of pyoderma gangrenosum (PG) that is more refractory to treatment. It is a cause of severe morbidity and poses a therapeutic challenge for the clinician. Infliximab (Remicade(R); Centocor, Malvern, PA, USA) is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha that has been proven to be effective in the treatment of inflammatory bowel disease (IBD) and rheumatoid arthritis. Currently, very few reports exist documenting its use in the treatment of PG and none in the treatment of PPG. We describe our experience of treating three patients with IBD-associated PPG with infliximab. All patients tolerated the drug without significant side-effects. Two patients with PPG recovered completely following the administration of infliximab, and one patient had a partial response to the drug. We conclude that infliximab appears to be a safe and effective therapeutic alternative in patients with PPG.

Mycophenolate mofetil may serve as a steroid-sparing agent for sarcoidosis.

Sarcoidosis is an inflammatory disease with potentially severe mucocutaneous manifestations. Mycophenolate mofetil (MMF) is an immunosuppressive drug extensively used in organ transplantation. Its use has been rapidly expanded into autoimmune and inflammatory diseases. We report the first successful and safe use of MMF in five patients with sarcoidosis.

Severe scleritis and urticarial lesions.

PURPOSE: To report the first known case of bilateral scleritis in a patient with hypocomplementemic urticarial vasculitis. DESIGN: Interventional case report. METHODS: Medical and ophthalmic history, results of physical and ophthalmic examinations, laboratory data, and histologic and immunopathologic examination were reviewed and results recorded. RESULTS: A 67-year-old man who presented with eye redness and pain, rash, arthralgia, and malaise was found to have hypocomplementemic urticarial vasculitis. Treatment with high-dose oral corticosteroids and mycophenolate mofetil resulted in the resolution of the rash and scleritis. CONCLUSIONS: Ocular involvement may be a helpful clue in the diagnosis of this uncommon syndrome.

Paraneoplastic pemphigus in children and adolescents.

BACKGROUND: Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous disease associated with specific B-cell lymphoproliferative neoplasms. There has been an increasing number of individual reports in the childhood and adolescent population. OBJECTIVES: To examine the clinical and immunopathological features of PNP occurring in children and adolescents. PATIENTS AND METHODS: We analysed the clinical and immunopathological findings of 14 patients under the age of 18 years with a confirmed diagnosis of PNP. Sera from all patients were analysed by indirect immunofluorescence (IF) and immunoprecipitation for plakin autoantibodies, immunoblotting for detection of plectin autoantibodies, and enzyme-linked immunosorbent assay (ELISA) for the detection of desmoglein (Dsg) 1 and Dsg3 autoantibodies. RESULTS: Severe oral mucositis was observed in all patients, and lichenoid cutaneous lesions in eight of 14 patients. The average age at presentation was 13 years. Striking findings included: pulmonary destruction leading to bronchiolitis obliterans in 10 patients, association with Castleman's disease in 12 patients, and a fatal outcome in 10 patients. The underlying neoplasm was occult in 10 patients. Histological findings include lichenoid and interface dermatitis with variable intraepithelial acantholysis. Deposition of IgG and C3 in the mouth and skin by direct IF was not found in some cases, but indirect IF detected IgG autoantibodies in all cases. Immunoprecipitation revealed IgG autoantibodies against desmoplakin I, envoplakin and periplakin in all cases, and against desmoplakin II and the 170-kDa antigen in 13 and 10 patients, respectively. Dsg3 and Dsg1 autoantibodies were present in 10 and three patients, respectively, and plectin autoantibodies in 13 patients. CONCLUSIONS: PNP in children and adolescents is most often a presenting sign of occult Castleman's disease. It presents with severe oral mucositis and cutaneous lichenoid lesions. Serum autoantibodies against plakin proteins were the most constant diagnostic markers. Pulmonary injury appears to account for the very high mortality rates observed.

Paraneoplastic pemphigus: a refractory autoimmune mucocutaneous disease.

BACKGROUND AND OBJECTIVE: We report on a 42-year-old man with Stage IIA non-Hodgkin's lymphoma who developed a severe mucocutaneous blistering eruption. His diagnosis, paraneoplastic pemphigus, was based on clinical, histological, and immunofluorescence findings and confirmed by immunoprecipitation. Despite maximal therapy with plasmapheresis, corticosteroids, and mycophenolate mofetil and the subsequent addition of cyclophosphamide and cyclosporine, the condition was fatal. CONCLUSION: This case illustrates the refractory nature of this disease and the inadequacy of existing therapies.

Bullous lesions in scleroderma.

BACKGROUND: The occurrence of bullous lesions in localized or systemic scleroderma is rare. Three histologic patterns have been reported: lichen sclerosus et atrophicus-like, lymphangiectatic blisters and autoimmune blistering diseases. OBJECTIVE: To investigate the frequency, clinical, and immunopathologic features of patients with scleroderma and bullous eruptions and to review the literature regarding this rare condition. METHODS: A retrospective study of 53 cases of scleroderma (localized, generalized, and systemic) in the dermatology and rheumatology clinics at one institution over an 8-year span. Clinical, serologic, and immunopathologic findings were analyzed in four cases. RESULTS: Four of 53 patients exhibited bullous lesions in association with scleroderma. The first case illustrates lymphangioma-like clinical and pathologic presentation. The second case demonstrates bullous lichen sclerosus et atrophicus-like pattern. The other two cases exemplify a superimposed autoimmune skin disease, epidermolysis bullosa acquisita and penicillamine induced pemphigus foliaceus after treatment for systemic scleroderma. CONCLUSIONS: Of the 53 original patients, we have described four cases of bullous scleroderma (7.5%) Illustrating several pathogenetic mechanisms of bulla formation. inflammatory (lichen sclerosus et atrophicus), fibrotic/obstructive (lymphangiomatous), autoimmune (epidermolysis bullosa acquisita), and pemphigus foliaceus. The final case illustrates bullae as a complication of therapy for the underlying scleroderma.

Discoid lupus erythematosus and cicatrizing conjunctivitis: clinicopathologic study of two cases.

BACKGROUND: Discoid lupus erythematosus (DLE) demonstrates both cutaneous and mucosal manifestations. Mucosal involvement is typically limited to the oral and anogenital mucosa. Conjunctival involvement in DLE is rare, especially in the absence of accompanying cutaneous disease. OBJECTIVE: We describe the clinical and immunopathologic features of two cases of cicatrizing conjunctivitis due to DLE. METHODS: In each patient, the clinical, immunopathologic, and serologic features were reviewed and the results recorded. RESULTS: Both patients presented with cicatrizing conjunctivitis suggestive of mucous membrane pemphigoid. Patient 1 had no history of typical DLE skin lesions. Patient 2 had a history of cutaneous and oral DLE prior to presentation. Histologic, electron microscopic, and direct immunofluorescence examination confirmed the diagnosis DLE in both patients. CONCLUSION: In patients presenting with cicatrizing conjunctivitis, DLE should be considered in the differential diagnosis. Performing appropriate investigations to distinguish conjunctival DLE from other autoimmune diseases with conjunctival involvement such as mucous membrane pemphigoid is critical in selecting an appropriate treatment regimen, in offering an accurate prognosis, and in monitoring for signs and symptoms of disease progression.

Pemphigus vulgaris: environmental factors. Occupational, behavioral, medical, and qualitative food frequency questionnaire.

BACKGROUND: There have been reports suggesting the involvement of environmental factors in the disease process of pemphigus. Factors suggested include exposure to pesticides or certain drugs. OBJECTIVE: To analyze the association of pemphigus with environmental exposure to various agents, including smoking, recreational and occupational insults, drugs, and food. DESIGN AND SETTING: In-person interviews of pemphigus patients and control subjects were conducted by trained medical investigators using a structured questionnaire. Questions included occupational, behavioral, medical, and qualitative food frequency details. The multicenter study was conducted at outpatient services of teaching hospitals in Bulgaria, Brazil, India, Israel, Italy, Spain, and the USA. PARTICIPANTS: A total of 126 pemphigus patients (55 men, 71 women; age, 54 +/- 17 years) and 173 healthy controls (87 men, 86 women; age 50 +/- 19 years) were interviewed in the period between October 1, 1999 and March 31, 2000. The diagnosis of pemphigus was based on clinical, histologic, immunohistologic, and immunohistochemical criteria. The disease duration was 2-27 years (8.4 +/- 7.2 years). Individuals with skin diseases other than pemphigus were selected as control subjects. MAIN OUTCOME MEASURE: Information on drugs, foods, and occupational, environmental, constitutional, and other possible risk factors was analyzed by t-tests and chi-squared tests as applicable. A multivariate logistic regression model was applied to the data to study simultaneously the independent relationship between each risk factor and pemphigus vulgaris. RESULTS: The risk for pemphigus vulgaris was lower for ex-smokers and current smokers than for patients who had never smoked. Exposure to pesticides and occupational exposure to metal vapor were associated with an increased risk of pemphigus. Pemphigus patients had more pregnancies than controls. There were differences in environmental factors between countries, with exposure to gardening materials and pesticides being highest among patients from Bulgaria, followed by Israel. Disease characteristics also exhibited differences between countries. Bulgarian patients less frequently had oral mucous membrane lesions: 66% compared to 92% for Israeli patients and 83% for Italians. The distribution of the disease in skin and mucous membranes was similar among patients from all countries. Exclusive skin involvement was seen in 50% of patients, mucous membranes alone in 23% of patients, and both skin and mucous membranes in 27% of patients. CONCLUSIONS: The beneficial effect of smoking on pemphigus might be explained by its effect on the immune system. In addition, smoking has an antiestrogenic effect, while pesticides have an estrogenic effect. The lower numbers of smokers among patients, the higher exposure rates to pesticides, and the higher number of female patients who had been pregnant may point to the contribution of estrogens to the disease process. It remains to be determined whether measures, such as avoiding exposure to pesticides or metal vapor, may be beneficial in the clinical context. As the present study was a survey, more definitive studies should be conducted to validate the results.

Chronic idiopathic acrocyanosis.

Acrocyanosis is an uncommon condition characterized by symmetric coolness and violaceous discoloration of the hands and feet. The nose, ears, lips, and nipples are also often affected. The disease is temperature dependent and generally worsens with cold exposure. Acrocyanosis is often secondary to a variety of underlying causes. We present a very interesting case of a 44-year-old woman with almost lifelong idiopathic acrocyanosis. Differential diagnoses are discussed in this article.

Treatment of resistant discoid lupus erythematosus of the palms and soles with mycophenolate mofetil.

Mycophenolate mofetil is an immunosuppressive drug that has recently been used to treat a variety of autoimmune and inflammatory skin diseases. Expanding the use of this agent in dermatology, we describe 2 patients with both systemic lupus erythematosus and discoid lupus erythematosus whose recalcitrant palmoplantar lesions were successfully treated with mycophenolate mofetil.

Clinical phenotype and anti-desmoglein autoantibody profile in paraneoplastic pemphigus.

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.

Nonendemic pemphigus foliaceus presenting as fatal bullous exfoliative erythroderma.

Pemphigus foliaceus is a cutaneous autoimmune blistering disease that is characterized by lower morbidity and mortality than those observed in pemphigus vulgaris or paraneoplastic pemphigus. However, erythrodermic forms of the endemic variant of pemphigus foliaceus have been associated with a higher mortality. We report a case of nonendemic pemphigus foliaceus that presented as fatal bullous exfoliative erythroderma, and thus, we will emphasize the inclusion of this entity in the differential diagnosis and the use of skin direct immunofluorescence in the evaluation of patients with erythroderma.

Paraneoplastic pemphigus without antidesmoglein 3 or antidesmoglein 1 autoantibodies.

Paraneoplastic pemphigus (PNP) is an autoimmune mucocutaneous blistering disease characterized by IgG autoantibodies that bind to various epithelia and immunoprecipitate a complex of 250, 230, 210, 190 and 170 kDa proteins. A recent study has suggested that PNP patients have antidesmoglein (Dsg) 3 autoantibody and that the antibody plays a pathogenic role in PNP. We report a 72-year-old woman with PNP associated with thymoma and adenocarcinoma of the lung. Diagnosis of PNP was made by the characteristic clinical, histological and immunopathological findings, as well as immunoprecipitation of characteristic 230, 210 and 190 kDa proteins. Using enzyme-linked immunosorbent assay with baculovirus-expressed recombinant proteins, the patient's serum was negative against both Dsg 3 and Dsg 1. This finding is unusual, and it suggests that the target antigen, which is involved in acantholysis, may be other than Dsg 3 in this case.