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.

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.

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.

"Essential" cutaneous vasculitis: what every rheumatologist should know about vasculitis of the skin.

Although the classification of small-and medium-vessel vasculitides involving the skin remains complex and imperfect, a substantial body of knowledge related to cutaneous vasculitis exists. Some components of this knowledge, though beyond the usual purview of rheumatologists, are essential to understanding the vasculitides. The correct interpretation of cutaneous findings combined with a properly performed skin biopsy yields important insights not only into underlying diagnoses, but also into the pathophysiological mechanisms of individual cases. In this review, we discuss a classification scheme for the cutaneous vasculitides, outline the work-up for evaluating patients with these disorders, and describe the essential features of the major categories of skin vasculitis.

Annular leukocytoclastic vasculitis associated with monoclonal gammopathy of unknown significance.

Leukocytoclastic vasculitis is a condition characterized by necrotizing neutrophilic inflammation of small dermal blood vessels usually resulting in palpable purpuric lesions. Leukocytoclastic vasculitis may be secondary to a variety of medications and underlying disease processes, including infections, connective tissue disorders, and malignancies. We describe a patient with a monoclonal gammopathy of unknown significance in whom leukocytoclastic vasculitis developed, manifested by a few prominent annular plaques on the lower extremity. The rare association between monoclonal gammopathy of unknown significance and leukocytoclastic vasculitis as well as the unusual annular presentation of the disease in this patient is discussed, and the relevant literature is reviewed.

Paraneoplastic pemphigus caused by an epithelioid leiomyosarcoma and associated with fatal respiratory failure.

A patient is described who initially presented with pemphigus vulgaris, limited to the oral cavity, and weight loss. Although the various laboratory studies pointed to the diagnosis of paraneoplastic pemphigus (PNP), the underlying neoplasm was not detected until 6 months later, when the patient developed shortness of breath and routine physical examination on admission revealed an abdominal mass, which eventually was proven to be an epithelioid leiomyosarcoma. In spite of radical excision of the tumour and intensive treatment of the dyspnoea, the patient died of respiratory failure 19 months after the PNP had been diagnosed. Early diagnosis of PNP is stressed to possibly prevent fatal pulmonary involvement.

Drug-induced linear immunoglobulin A bullous disease that clinically mimics toxic epidermal necrolysis.

Drug-induced linear immunoglobulin A bullous disease is a subepidermal blistering disorder that most commonly occurs after exposure to vancomycin. It can clinically mimic toxic epidermolytic necrolysis. We describe an 87-year-old white woman in whom linear immunoglobulin A bullous disease developed while she was taking vancomycin and phenytoin. A few days after the linear immunoglobulin A bullous disease developed, both medications were discontinued. No new bullae developed, and the eruption completely resolved within 2 weeks. The patient was treated with only topical therapy.

Mycophenolate mofetil in the treatment of severe skin manifestations of dermatomyositis: a series of 4 cases.

Four cases with classic skin manifestations and histologic evidence of dermatomyositis are presented. No occult malignancies were found. After conventional therapy with corticosteroids, hydroxychloroquine and/or methotrexate proved to be limited by side effects or an inadequate clinical response, a therapeutic trial of mycophenolate mofetil was instituted. This relatively new drug, which inhibits lymphocyte proliferation, was effective [with a mean duration of treatment of 13 months (range 6-20)] at controlling cutaneous disease activity, resulting in a decrease of the steroid dose.

Lichenoid dermatitis in paraneoplastic pemphigus: a pathogenic trigger of epitope spreading?

BACKGROUND: In select cases, lichen planus has been observed to be a paraneoplastic condition sometimes associated with paraneoplastic pemphigus, a disease featuring autoantibodies directed against plakin proteins, desmogleins 3 and 1, and a still uncharacterized 170-kd antigen. Epitope spreading describes the phenomenon where underlying chronic inflammation leads to the sequential recognition of new epitopes on self-proteins over time. OBSERVATIONS: Five of 6 patients diagnosed as having paraneoplastic pemphigus had concomitant clinical and histological features of lichen planus. In 1 patient, results of the initial indirect immunofluorescence on rat bladder were negative and only 2 of the 5 antigens were identified by immunoprecipitation. After 1 year of worsening disease, repeated testing confirmed the presence of antibodies directed against all 6 of the implicated antigens, supportive of our hypothesis that epitope spreading may occur in paraneoplastic pemphigus. CONCLUSIONS: Lichenoid eruptions may predispose to an early evolutionary stage of paraneoplastic pemphigus. Cell-mediated autoimmunity at the dermoepidermal junction may promote the exposure of self-antigens and the development of subsequent and progressive humoral autoimmunity. As such, paraneoplastic pemphigus may demonstrate epitope spreading in a human, humoral-mediated autoimmune disease.

KID syndrome associated with features of ichthyosis hystrix.

Keratitis-ichthyosis-deafness (KID) syndrome is a congenital ectodermal disorder causing erythrokeratoderma, vascularizing keratitis, and neurosensory deafness. Ichthyosis hystrix is a rare cutaneous disease characterized by well-demarcated, spiky, verrucous, linear plaques that is believed to be a clinical and pathologic chimera of two autosomal dominant diseases: epidermal nevus and epidermolytic hyperkeratosis. We present a patient with the classic triad of KID syndrome with clinical and histologic features of ichthyosis hystrix. This case demonstrates that KID syndrome comprises a spectrum of ectodermal disorders which may include diseases such as hystrix ichthyosis and deafness (HID) syndrome.