Conleth A. Egan

Linear IgA Bullous Dermatosis

Linear IgA bullous dermatosis (LABD) is a unique autoimmune blistering disease which can present both in children and adults. There are various clinical presentations of the disease which can involve both cutaneous and mucosal tissues. LABD has been reported to be associated with medications, ulcerative colitis, and malignancies. This chapter will discuss the diagnosis, current therapies, and possible treatment algorithms for managing LABD patients.

Plasmapheresis as an adjunct treatment in toxic epidermal necrolysis.

BACKGROUNDnToxic epidermal necrolysis (TEN) is a severe, progressive disease characterized by the sudden onset of skin necrosis. It is frequently associated with systemic involvement and has a high rate of morbidity and mortality. Standard therapy includes meticulous wound care, fluid replacement, and nutritional support in an intensive care setting.nnnOBJECTIVEnWe evaluated the outcomes of patients treated in a burn unit for TEN over a 9-year period and compared the outcomes of a subset of patients treated with plasmapheresis with those managed by conventional means.nnnMETHODSnThe records of 16 patients with a diagnosis of TEN obtained from a computerized database were reviewed. Parameters recorded included extent of body surface area involvement and number of mucous membranes involved at admission, complications such as sepsis or need for mechanical ventilation, length of stay, and disposition.nnnRESULTSnSixteen patients were included in this study. Ten were treated with conventional support measures alone. Six were treated with plasmapheresis. The average age was 42.4 years; the male/female ratio was 1:2.2. Sulfamethoxazole/trimethoprim was implicated in causation in 6 patients. The average extent of involvement on admission in all patients was 51.5% total body surface area. The average length of stay in all patients was 14.8 days. Eight patients (50%) were discharged home, 4 (25%) were discharged to a rehabilitation facility, and 4 (25%) died (2 of sepsis, 2 of cardiopulmonary arrest). None of the plasmapheresis-treated patients died.nnnCONCLUSIONnPlasmapheresis is a safe intervention in extremely ill TEN patients and may reduce the mortality in this severe disease. Prospective studies are needed to further define its usefulness.

Cutaneous malignant melanoma and oculodermal melanocytosis (nevus of Ota): Report of a case and review of the literature

A 29-year-old white man, with oculodermal melanocytosis, had a rapidly enlarging, erythematous, painful nodule over his left brow, within the nevus. The lesion was excised and diagnosed as a malignant melanoma. Systemic evaluation showed no evidence of distant disease. This is the tenth case reported of a cutaneous melanoma developing in a nevus of Ota. Melanoma arising in the choroid, brain, orbit, iris, ciliary body, or optic nerve in association with a nevus of Ota is well documented. Careful observation is necessary in patients with a nevus of Ota, particularly in white patients, in whom malignant degeneration seems to occur with a disproportionate frequency.

Low-dose oral methotrexate treatment for recalcitrant palmoplantar pompholyx

We describe 5 patients with severe pompholyx who did not respond to conventional therapy or who had debilitating side effects from corticosteroids. Low-dose methotrexate was added to their treatment regimens and led to significant improvement or clearing with a favorable side-effect profile. In all 5 patients the need for oral corticosteroid therapy was substantially decreased or eliminated, thus decreasing potential corticosteroid-induced morbidity. In this uncontrolled series of patients with recalcitrant palmoplantar pompholyx, methotrexate was an effective treatment and acted as a steroid-sparing agent.

Linear IgA bullous dermatosis responsive to a gluten-free diet

Dermatitis herpetiformis is associated with a gluten-sensitive enteropathy in >85% of cases. Both the skin lesions and the enteropathy respond to gluten restriction. Linear IgA bullous dermatosis has a much lower prevalence of histological small bowel abnormalities, and lesions are not known to respond to gluten restriction. We report a patient with linear IgA bullous dermatosis and gluten-sensitive enteropathy. This report addresses the issue of whether linear IgA bullous dermatosis can be associated with gluten-sensitive enteropathy. We evaluated the response to gluten restriction and normal diet by following the status of the patients jejunal biopsies and skin lesions. The patient responded to gluten restriction, as shown by resolution of jejunal abnormalities and skin lesions and subsequently by recurrence of jejunal abnormalities and skin lesions with reinstitution of a gluten-containing diet. This report demonstrates that linear IgA bullous dermatosis can respond to gluten restriction if an underlying gluten-sensitive enteropathy is present.

IgA1 is the major IgA subclass in cutaneous blood vessels in Henoch–Schönlein purpura

Henoch–Schönlein purpura (HSP) is characterized by palpable purpura predominantly involving the lower extremities. On direct immunofluorescence IgA can be seen deposited in the blood vessel walls of the superficial dermis. The subclass distribution of antibodies to this IgA was studied in the biopsies of 28 patients with HSP by direct immunofluorescence using anti‐IgA1 and anti‐IgA2 specific monoclonal antibodies. All 28 patients’ biopsies demonstrated deposition of IgA1 while only one patient had IgA2 deposition. Positive and negative controls stained appropriately. This demonstrates that IgA1 is the dominant IgA subclass found in the skin in Henoch–Schönlein purpura.

The Immunoglobulin A Antibody Response in Clinical Subsets of Mucous Membrane Pemphigoid

Background: Mucous membrane pemphigoid (MMP) is an immunobullous disease. In MMP there is frequently a mixed antibody response with the presence of IgA and/or IgG antibodies directed toward basement membrane zone antigens. The IgG antibody response in MMP has been studied, but the antigens to which the IgA antibodies react have not been studied. Objective: To determine the IgA autoantibody reactivity profiles in patients with MMP. Methods: Patients who had both ocular and oral MMP were compared with patients who had ocular or oral MMP and with patients who had cutaneous linear IgA disease (LABD) by Western immunoblot studies. Results: Five of 15 MMP patients and 1 of 5 LABD patients had IgA antibodies reactive with the 180-kD bullous pemphigoid antigen. Seven of 15 MMP patients had IgA antibodies reactive with the 97-kD LABD antigen. Conclusion: Major antigens in IgA MMP are the 180-kD bullous pemphigoid antigen and the 97-kD LABD antigen.

Plasmapheresis as a steroid saving procedure in bullous pemphigoid.

Background Bullous pemphigoid is an immunobullous disease affecting predominantly older patients. In severe cases, high‐dose corticosteroids and/or other immunosuppressants are often needed long term to control the disease. These can be associated with serious side‐effects in this patient population.

Characterization of the antibody response in oesophageal cicatricial pemphigoid

Cicatricial pemphigoid (CP) is a subepidermal, autoimmune bullous dermatosis. It is classified as a clinical subset of bullous pemphigoid (BP). However, it differs from BP in some significant ways: (i) in CP mucosal involvement with clinical scarring is prominent; (ii) there is a prominent IgA class antibody response alone or in addition to the IgG class antibody response; and (iii) there is a heterogeneous antibody response in CP, whereas in BP the majority of the antibodies are directed against a 180‐kDa hemidesmosomal protein, bullous pemphigoid antigen 2 (BPAg2). Oesophageal involvement in CP is a rare, but often devastating manifestation. In this study we examined the humoral autoimmune response in oesophageal CP, in an attempt to characterize the autoantibody reactivity profile. We used direct and indirect immunofluorescence and Western immunoblotting using normal human skin and oesophagus substrates. We studied patient sera over time in order to search for evidence of epitope spreading in these patients. All patients had positive direct immunofluorescence of perilesional oesophageal epithelium. All patients had positive circulating antibasement membrane zone autoantibody titres. There was a significant IgA class in addition to an IgG class autoantibody response. IgA and IgG antibodies demonstrated significant reactivity with BPAg2 and the 97u2003kDa linear IgA disease antigen on Western immunoblot suggesting intraprotein epitope spreading. There was no evidence of interprotein epitope spreading over time. Our findings suggest that there is a heterogeneous antibody response in oesophageal CP with the predominant antigen being BPAg2.

Neurologic variant of epidermal nevus syndrome with a facial lipoma

A 1‐year‐old girl presented for evaluation of a linear plaque on her forehead. She was born at 36u2003weeks gestation following an uncomplicated pregnancy and delivery. At birth, she was noted to have an enlarged right cheek. She had no seizure history, but developed grand mal seizures 1u2003year later.