A Case of Successful Management of Adult-Onset Linear IgA Bullous Disease With Sulfasalazine During the COVID-19 Pandemic.

Linear IgA bullous disease (LABD) is a rare, acquired, autoimmune, pruritic, and blistering skin condition. Dapsone is a first line treatment option, however, there are limited options if this fails, or if contraindicated. We present a case of successful management of LABD with sulfasalazine. A 46-year-old Caucasian female with LABD was commenced on high dose corticosteroids. She failed to wean, and dapsone was contraindicated due to a history of primary sclerosing cholangitis and risk of hepatitis. Following the failure of mycophenolate mofetil, sulfasalazine was trialed and successfully controlled both this patient’s LABD and ulcerative colitis. There is little literature on the use of sulfasalazine in dermatological conditions. We present sulfasalazine as an option for patients who are unable to use classically used treatments for LABD, or in those who have a dual diagnosis, as in this case, allowing for one agent to manage both conditions. Furthermore, The National Institute for Health and Care Excellence guidance mentions sulfasalazine as one of the few drugs that can be continued during the COVID-19 pandemic, and its use spared this patient from the significant immunosuppression associated with other treatment modalities.J Drugs Dermatol. 2022;21(12): doi:10.36849/JDD.6717.

Linear IgA Bullous Dermatosis Preceding the Diagnosis of Primary Sclerosing Cholangitis and Ulcerative Colitis: A Case Report.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune blistering disorder seen in the pediatric and adult populations that is often linked to a medication, infection, or underlying gastrointestinal, hepatobiliary, or autoimmune disease. In this study, we describe the case of a 23-year-old white man whose presentation and diagnosis of LABD ultimately led to the discovery of underlying primary sclerosing cholangitis (PSC) and ulcerative colitis (UC). His dermatitis resolved with topical steroids and dapsone, and he is undergoing systemic treatment for his UC and PSC. This exceptional case further validates the association between LABD with UC, strengthens that with PSC, and underscores the importance of alerting clinicians to consider conducting a systemic workup in addition to thorough medication history on making the diagnosis of LABD.

Linear IgA bullous dermatosis associated with ulcerative proctitis: treatment challenge.

Linear IgA bullous dermatosis is a rare bullous disease in children and adults that can be associated with autoimmune conditions, malignancies, infections, or medication exposure. The definitive diagnosis relies on the biopsy. A 58-year-old man presented to our clinic with a pruritic vesicular and bullous eruption. Histology showed the classic findings of a subepidermal blister with neutrophilic infiltrate and linear IgA deposition along the dermal-epidermal junction. Upon further evaluation, he was diagnosed with ulcerative proctitis. His therapy was complicated owing to side effects and lack of response to the standard treatment options. Dapsone, a first-line therapy, caused symptomatic methemoglobinemia whereas niacinamide with doxycycline were not effective. He required intravenous and oral steroids to reach improvement followed by transitioning to methotrexate.

Linear IgA bullous disease presenting as toxic epidermal necrolysis: a case report and review of the literature.

A 91-year-old female presented with widespread skin sloughing and bullae clinically mimicking toxic epidermal necrolysis (TEN). The patient was on multiple antibiotics, including vancomycin and piperacillin/tazobactam. Histopathology and direct immunofluorescence were consistent with a diagnosis of linear IgA bullous disease (LABD). In a PubMed review of the literature from 1975 to the present, there have been 15 cases of LABD presenting as TEN clinically and with characteristic linear IgA deposits on direct immunofluorescence studies. Vancomycin and phenytoin were the most commonly implicated medications. Twelve patients saw a resolution or healing of skin lesions after discontinuation of the implicated medication. There were, however, 5 patients who died of complications related to their comorbidities. It is important to include LABD in the differential diagnosis when evaluating patients who clinically present with TEN.

Association of linear IgA bullous disease with ulcerative colitis: a case of successful treatment with infliximab.

Linear IgA bullous disease (LABD) has been reported in association with inflammatory bowel disease, in particular ulcerative colitis (UC). We reporting a 34-year-old female who developed LABD during a flare-up of UC. We administered infliximab, which has been approved for the treatment of UC; infliximab dramatically improved the cutaneous lesions and bowel symptoms. This is the first report showing a marked effect of infliximab on LABD. First, we hypothesize that infliximab works for UC and then calms down excessive production of inflammatory cytokines and autoantibodies, and so stricter control of UC by infliximab is beneficial against the skin condition of LABD. Second, we suggest that TNF-α production in the lesion of LABD is increased, so TNF-α plays an important role in developing cutaneous lesions. This case suggests that infliximab, a monoclonal antibody against TNF-α, is efficacious in the cutaneous symptoms of LABD.

Interstitial pneumonia associated with linear immunoglobulin A/immunoglobulin G bullous dermatosis.

A 76-year-old man with interstitial lung disease was admitted to our institution after developing persistent dyspnea upon effort. He also had a relapse of bullous eruptions on the skin of the trunk and extremities, previously diagnosed as vesicular pemphigoid. Direct immunofluorescence of a skin biopsy specimen using fluorescence microscopy showed the linear deposition of immunglobulin A (IgA), IgG and C3 along the basement membrane. These findings indicated a definitive diagnosis of linear IgA/IgG bullous dermatosis. Chest computed tomography, bronchoalveolar lavage and transbronchial lung biopsy findings suggested nonspecific interstitial pneumonia. Direct immunofluorescence of the lung biopsy specimens using fluorescence microscopy also showed a deposition of IgA, IgG and C3 along the epithelial cell membranes and basement membranes of the bronchioles and alveoli. Lung disorders associated with linear IgA/IgG bullous dermatosis are extremely rare and, to our knowledge, this is the first report of such a case of interstitial pneumonia.

Linear IgA bullous dermatosis: an unusual cause of upper eyelid cicatricial entropion.

Chronic cicatrizing conjunctivitis is a relatively uncommon condition resulting in significant ophthalmic morbidity, including keratoconjunctivitis sicca, cicatricial entropion, trichiasis, corneal scarring, significant discomfort, and visual loss. The potential causes of cicatrizing conjunctivitis are varied and include commonly encountered entities such as ocular cicatricial pemphigoid, Stevens-Johnson syndrome, and trachoma and many more rare causes which are particularly difficult to diagnose and treat and may not be familiar to the ophthalmologist. The authors herein present a case of chronic cicatrizing conjunctivitis, cicatricial entropion, and trichiasis caused by a rare entity called linear IgA bullous dermatosis. The case presentation conforms to the tenets of the Declaration of Helsinki and is Health Insurance Portability and Accountability Act compliant. This chronic dermatosis has a varied presentation, and the ophthalmic manifestations in particular have been infrequently described. This case demonstrates the benefits of immunohistochemistry in diagnosis and the difficulties in medical and surgical management of linear IgA bullous dermatosis while underscoring the lifelong difficulties in managing chronic inflammatory conditions causing ocular cicatrization.

Linear IgA bullous dermatosis in an acute myeloid leukemia patient: a rare case report.

Linear IgA bullous dermatosis (LABD) is a rare autoimmune bullous disease characterized by linear IgA deposition along the skin basal membrane. In children, LABD classically presents with a "cluster of jewels" appearance, whereas in adults the classic presentation is itchy papules with tense vesicles and bullae on an erythematous base. We report the case of a 41-year-old woman with LABD that we suspect was induced by acute myeloid leukemia presenting with multiple vesicles and bullae that coalesced, forming the typical clinical manifestation of LABD and confirmed with histopathological and direct immunofluorescence. The patient was treated with a combination of oral and topical corticosteroids with excellent results.

Ulcerative colitis complicated with linear immunoglobulin A bullous dermatosis.

Linear immunoglobulin A (IgA) bullous dermatosis (LABD) is a rare disorder involving subepidermal blistering characterised by IgA deposition along the basement membrane. The clinical features of LABD are variable but can include bullae, vesicles and erythematous lesions. Histopathology reveals formation of subepidermal bullae and linearly deposition of IgA in the basement membrane of the epidermis. LABD has been reported as a rare complication of ulcerative colitis (UC). We report the case of a young woman with UC complicated by LABD. The latter manifested as vesicles with erythema on almost the entire body. A biopsy of the skin lesions revealed linear IgA deposits in the basement membrane according to a direct immunofluorescence assay. Prednisolone administration resulted in clinical remission of UC but poor improvement of skin lesions. Oral administration of diaminodiphenyl sulfone led to improvement of blisters. Thereafter, abdominal and skin symptoms did not recur and she was discharged from hospital.

A Case of Possible Concurrence of Dermatitis Herpetiformis and Linear Immunoglobulin A / Immunoglobulin G Bullous Dermatosis.

Dear Editor, Linear immunoglobulin (Ig) A bullous dermatosis (LABD), one subtype of subepidermal autoimmune bullous skin diseases (AIBDs), is characterized by linear deposit of only IgA along the basement membrane zone (BMZ) on direct immunofluorescence (DIF) (1,2). Patients showing linear deposits of both IgA and IgG are diagnosed with linear IgA/IgG bullous dermatosis (LAGBD) (3,4). Dermatitis herpetiformis (DH) is another type of subepidermal AIBD characterized by clinically pruritic erythematous skin lesions with vesicles on the elbows, knees, and buttocks with granular IgA deposits of IgA by DIF (5). In this study, we report a Japanese case of a patient who showed possible concurrence of DH and LAGBD based on clinical, histological, and immunological findings. A 72-year-old Japanese man who had a past history of dyslipidemia and resected lung cancer but was not taking any medicines, presented with a one-year history of blistering skin lesions. Physical examination revealed erythemas and peripherally arranged vesicles and erosions on the bilateral elbows, knees, and the buttock (Figure 1, a-c). Mucous membranes were not involved. The results of all laboratory tests were within normal ranges, except for increased serum IgA level 351 mg/dL (normal ranges; 46-260 mg/dL). Skin biopsy histopathologically showed subepidermal blisters infiltrated with neutrophils and eosinophils (Figure 1, d). DIF showed deposits of IgG, IgA, and complement component 3 along the BMZ mainly in granular but partially in a linear pattern (Figure 1, e-g). Circulating IgG (Figure 1, h) and IgA (Figure 1, i) autoantibodies were not detected by indirect immunofluorescence (IIF) of normal skin, however, circulating IgA (Figure 1, j) but not IgG (Figure 1, k) antibodies were bound to both the epidermal and dermal sides by IIF of 1M NaCl-split normal skin. Commercially available enzyme-linked immunosorbent assays (ELISAs) for BP180 NC16a domain, BP230, and type Vll collagen (MBL, Nagoya, Japan), showed negative results for both IgG and IgA antibodies. IgG in-house ELISA for full length BP180 was also negative. IgG and IgA immunoblotting analyses of different antigen sources, including normal human epidermal and dermal extracts, recombinant proteins of NC16a, and C-terminal domains of BP180 region, BP230, purified laminin 332, and concentrated culture supernatant of HaCaT cells for LAD-1, were all negative. IgA ELISAs of tissue- and epidermal-transglutaminases were negative (1.92 AU/mL and 20.98 AU/mL, respectively; normal range <22.0 AU/mL). The patient was successfully treated with only topical corticosteroids with occasional mild local relapses. Japanese DH is different from European DH in some respects, i.e., DH is very rare in Japan due to genetic/HLA difference, absence of celiac disease, and frequent fibrillar IgA deposition in DIF. Therefore, we believe that this case is interesting as a rare Japanese DH case with complicated conditions. The clinical and immunochemical characteristics in the present case were compatible for both DH and LAGBD. Clinical features of vesicles on erythemas on the knees and buttock suggested DH, while histopathological features were compatible with LAGBD but also with DH, DIF results suggested both LAGBD and DH, and the results of IIF of 1M NaCl-split skin suggested LAGBD. All biochemical studies for autoantigens were negative, which suggested DH. However, autoantigens are not clearly detected in many LAGBD cases, either. IgA anti-epidermal transglutaminase antibody, a DH marker, was negative, but the titer was relatively high but within normal range. Therefore, we considered that this case might have developed DH and LAGBD concurrently. However, there may be two other possibilities: [1] this case was DH and non-pathogenic circulating autoantibodies were secondary production, and [2] LAGBD cases may sometimes show granular-linear BMZ deposition of IgG and IgA. Future studies on similar cases are needed to clarify our speculations.

Ten-year follow-up study of linear immunoglobulin A dermatosis complicated with ulcerative colitis.

Linear immunoglobulin A dermatosis (LAD) is rarely complicated in patients with ulcerative colitis (UC), though the long-term prognosis in those with concurrent LAD and UC is not fully understood. Here, we report findings obtained in follow-up examinations performed over a 10-year period of a UC patient initially complicated with LAD. We treated an 18-year-old male for relapse of UC with deteriorating blisters diagnosed as LAD. Following successful induction therapy for both UC and LAD with oral prednisolone, the patient was followed for 10 years. Skin condition remained good at each examination, even with second and third relapses of UC. Our findings in this case indicate that LAD is rarely complicated with UC, while it has no association with colitis disease activity. Furthermore, adequate treatment following an initial diagnosis of LAD is important for management of affected UC patients.