A case of anti-laminin γ1 (p200) pemphigoid developed after dipeptidyl peptidase-4 inhibitor administration.

A 73-year-old man with diabetes mellitus was referred to our department for ultraviolet treatment for erythematous skin lesions with itching. On dipeptidyl peptidase-4 inhibitor (DPP-4i) sitagliptin (Januvia®) for diabetes mellitus, the erythematous skin lesions appeared and spread to the whole body. At the initial visit, erythema multiforme-like skin lesions with crusts were observed on the trunk and extremities, and the patient was suspected to have drug eruption. Histopathology demonstrated eosinophilic infiltration in the superficial dermis and inflammatory cell infiltration in the epidermis. Sitagliptin was discontinued, and erythematous lesions improved with oral prednisolone. Thereafter the patient was treated with phototherapy and  betamethasone sodium phosphate infusion for residual prurigo. However, blistering skin lesions appeared 5 months later. Histopathological findings were subepidermal blisters with eosinophilic abscess, and bullous pemphigoid was suspected. CLEIAs for autoantibodies to desmoglein 1 (Dsg1), Dsg3 and BP180 were negative. Direct immunofluorescence showed linear depositions of immunoglobulin G (IgG) and C3 at the epidermal basement membrane zone, and indirect immunofluorescence detected IgG anti-epidermal basement membrane zone antibodies, reacting with the dermal side of 1M NaCl-split normal human skin. IgG antibodies reacted with 200 kDa laminin γ1 (p200) by immunoblotting using dermal extracts. These results indicated that this patient was diagnosed with anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration. Although reports of DPP-4i-related bullous pemphigoid have accumulated, cases of anti-laminin γ1 (p200) pemphigoid developed after DPP-4i administration are rarely reported.

A case report of steroid-refractory bullous pemphigoid induced by immune checkpoint inhibitor therapy.

The widespread use of immune checkpoint inhibitors in several malignancies has revealed new immune-related adverse events. Bullous pemphigoid (BP) is an antibody-driven autoimmune disease characterized by skin inflammation and fluid-filled bullae. Herein, a 69-year-old man with lung squamous cell carcinoma developed multiple vesicles and tense bullae 3 weeks after the initiation of a programmed death-1 (PD-1) inhibitor, pembrolizumab, and chemotherapy. Biopsy revealed a subepidermal bulla with lymphocytic and eosinophil infiltration, and immunohistochemical studies predominantly showed CD4+ cells, a few CD8+ cells, and the occasional CD20+ lymphocyte. The serum anti-BP180 antibody level, as well as the interleukin-6 and interleukin-10 levels, were elevated compared to the lower levels of tumor necrosis factor-α. Eosinophil levels were high and consistent with the development of blisters. A diagnosis of BP associated with PD-1 inhibitor therapy was made, and the Common Terminology Criteria for Adverse Events classification was grade 3. Immunotherapy was permanently discontinued, and the patient's bullous lesions failed to react to high-dose systemic corticosteroids combined with minocycline and niacinamide. Intermittent blister recurrence occurred in 2 months, eventually improving with the administration of two courses of intravenous immunoglobulin. At 5 weeks of follow-up, the patient's tumor was reduced on a computed tomographic scan. Despite stable BP treatment, however, he repeatedly developed complications due to the complexity of his underlying disease and could not be treated with anti-tumor therapy. Early recognition and management of serious immune-related bullous dermatologic toxicity are essential for patient safety.

The associations between bullous pemphigoid and drug use: a UK case-control study.

OBJECTIVE: To explore associations between bullous pemphigoid (BP) and previous drug use in the United Kingdom. DESIGN: A case-control study comparing the drug history of consecutive patients with BP and control subjects. SETTING: Tertiary care center for immunobullous diseases and skin tumor clinics at Oxford University Hospitals. PATIENTS OR OTHER PARTICIPANTS: Eighty-six consecutive BP patients and 134 consecutive controls from the same region and similar in age and sex who presented with other dermatological diagnoses. MAIN OUTCOME MEASURES: Crude and adjusted odds ratios and 95% confidence interval of BP in relation to each drug. RESULTS: Loop diuretics were used significantly more frequently by the BP patients (crude odds ratio, 2.4 [95% CI, 1.2-5.0; P= .02]; adjusted odds ratio, 3.8 [1.5-9.7; P= .006]). No significant differences were found between groups for use of other diuretics, aspirin, antidepressants, antiepileptics, antihypertensives, or central nervous system agents (eg, antipsychotics). Patients with BP used calcium or vitamin D supplements, antibiotics, antihistamines, and prednisolone significantly more often on multivariate analysis. CONCLUSIONS: The findings of our study demonstrate increased use of loop diuretics in patients with BP before the development of BP. The mechanism behind such an association clearly warrants further investigation.

Localized bullous pemphigoid induced by photodynamic therapy.

Topical photodynamic therapy (PDT) causes localized phototoxicity and has been shown both in vitro and in humans to have immunomodulatory and immunosuppressive effects. We report a case of localized bullous pemphigoid (BP) developing after PDT. Although BP has been reported to develop following cutaneous insults such as surgery, radiotherapy, psoralen ultraviolet A (PUVA) and ultraviolet B phototherapy, PDT has not previously been reported as a trigger. Possible mechanisms include direct mechanical injury to the basement membrane and subsequent autoantibody formation, an indirect immunomodulatory effect of PDT, or most likely, precipitation of BP in individuals with pre-existing low titres of epidermal autoantibodies (so-called subclinical BP). PDT should be added to the list of possible exogenous triggers for BP and this condition should be considered if blistering develops following PDT.

Bullous pemphigoid in an infant using complementary medicine.

Bullous pemphigoid (BP) is an acquired immunobullous disorder rarely seen in childhood. We report the case of an infant with BP successfully treated with oral corticosteroids. The onset of BP was associated with use of complementary medications and we speculate that these may have been triggering factors.

Lichen planus pemphigoides associated with Chinese herbs.

We report a 62-year-old Chinese woman with a 2-year history of lichen planus presenting with extensive violaceous maculopapules and plaques 1 week after taking an oral preparation of Chinese herbs. The patient developed vesiculobullous skin lesions 7 weeks later. Histopathological examination showed subepidermal blisters and adjacent bandlike lymphocytic infiltration. Direct immunofluorescence revealed linear deposits of IgG and C3 along the basement membrane zone. Indirect immunofluorescence showed IgG antibody deposition along the epidermal side of salt-split human skin. Circulating anti-bullous pemphigoid 180 antibodies were detected by ELISA. Lichen planus pemphigoides (LPP) was diagnosed. To our knowledge, this is the first report of LPP associated with oral Chinese herbs.

Bullous pemphigoid induced by PUVA therapy.

An 80-year-old psoriatic patient developed a blistering eruption during oral PUVA therapy. The diagnosis of bullous pemphigoid (BP) was established by routine histopathology, which demonstrated subepidermal blistering, and direct immunofluorescence, which revealed linear deposits of IgG, IgM and C3 along the basement membrane zone. Indirect immunofluorescence using normal human split skin revealed binding of IgG antibodies to the epidermal side, thus confirming a subepidermal blistering disorder. These proteins were identified by the immunoblotting technique as BP antigens I and II. Clinically, the lesions could be reproduced by phototesting using topical 8-methoxypsoralen. Again, the histopathological and immunopathological findings were consistent with the diagnosis of PUVA-induced BP. To the best of our knowledge, this is the first report demonstrating psoriasis-associated BP, in which the clinical diagnosis of BP is confirmed by immunoblotting analysis. The exact role of UV light in precipitating bullous lesions, particularly the question whether UV light may represent an unspecific epidermal injury leading to further attraction of autoantibodies to the basement membrane zone, as suggested recently by an experimental study in rodents, remains to be clarified in future studies.

[Bullous pemphigoid induced by photochemotherapy of psoriasis. Apropos of 2 cases, with a review of the literature]. / Pemphigoïde bulleuse induite par la photochimiothérapie du psoriasis. A propos de 2 cas, avec revue de la littérature.

PUVA-induced generalized bullous pemphigoid is reported is 8 patients with psoriasis and compared with the bullous pemphigoid described in 25 patients treated by other techniques (Goeckerman, UVB, anthralin, sun exposure, topical steroids). Furthermore they must be differentiated from all the other types of bullae induced by photochemotherapy in psoriatic patients. Diagnostic criteria should be improved in order to allow a better classification of these bullous diseases and to separate the photo-toxic bullae which are the commonest, from other bullae such as epidermolysis bullosa acquisita, localized bullous pemphigoid and drug-induced bullous pemphigoid.