Bullous Pemphigoid Induced by Metamizole in a Pediatric Patient.

Bullous pemphigoid (BP) is an autoimmune bullous disease commonly seen in adult population but rarely encountered in the pediatric population. Although the exact etiology of BP remains unclear, various vaccines, infectious agents, and drug use have been blamed in the etiology of BP. Here, we present a 14-year-old patient who developed BP after using metamizole and whose diagnosis was clinically and histopathologically confirmed.

Introduction

Bullous pemphigoid (BP) is a subepidermal autoimmune bullous dermatosis characterized by linear deposition of immunoglobulin G (IgG) and C3 along the dermoepidermal junction. BP180 and BP230 are major antigens in patients with BP.[1]

Case Report

A previously healthy 14-year-old boy presented to our clinic with the complaints of bullous lesions in the face, scalp, neck, upper chest, and back. The patient noticed the lesions 24 h after receiving intramuscular metamizole due to the complaint of headache. The patient had no systemic symptom except for itching and had no history of infection or other drug use within the last 1 month. Moreover, he had no family history of bullous disease. Skin examination revealed multiple tense bullae in the face, scalp, neck, upper chest, back, and genital region. In addition, numerous targetoid lesions were also present on the back [Figures 1a–c]. No lesion was detected in the oral mucosa. Routine laboratory workup including complete blood count and liver function tests was normal. Histopathologic evaluation of the lesion site indicated subepidermal disintegration and lymphocyte infiltration accompanied by eosinophils in the upper dermis [Figure 2a]. Direct immunofluorescence (DIF) test of the perilesional area revealed a linear deposition of IgG and C3 in the basal membrane [Figure 2b and c]. The patient was diagnosed as having pediatric BP depending on the clinical, histopathologic, and immunofluorescence findings. The patient was initiated on oral methylprednisolone (1 mg/kg/day) and all the lesions resolved within the first 3 days. At week 1, the methylprednisolone treatment was gradually terminated. No recurrence occurred within the 10-month follow-up.

Figure 1

(a) Multiple tense bullae in the face, scalp, neck, and upper chest; (b) multiple tense bullae and numerous targetoid lesions on the back and (c) multiple tense bullae in the genital region

Figure 2

(a) Subepidermal disintegration (large arrow) and lymphocyte infiltration accompanied by the eosinophils in the upper dermis (small arrow) (H and E; ×200) (b) direct immunofluorescence showing linear deposition of immunoglobulin G in the epidermal basement membrane (×100) (c) direct immunofluorescence showing linear deposition of C3 in the epidermal basement membrane (×100)

Discussion

BP is an autoimmune subepidermal bullous disease frequently seen in elderly patients and rarely encountered in pediatric patients.[2] The incidence of pediatric BP remains unclear. Pediatric BP has two peak incidences, one in the 1st year of life and the other at around 8 years of age.[3] BP is seen equally in women and men in adult patients, whereas it is more common in girls in pediatric patients.[4]

BP has different clinical manifestations; the face, palms, and soles are commonly involved in children aged less than a year, whereas these regions are rarely affected in older children. Although the involvement of the genital region is rarely seen in newborn children, it is presented by almost 50% of older children, mostly in girls. In addition, BP may be limited to the genital region alone in some patients.[3]

The exact pathogenesis of BP remains unknown. However, in the literature, BP has been reported after the first set of vaccinations (tetanus, diphtheria, pertussis, and polio) and hepatitis B vaccine.[12] In addition, a BP case that developed after homeopathy treatment including sulfur, mercury, and Rhus (Toxicodendron) had also been reported.[5] The literature also shows that BP may be triggered by infectious factors such as scabies in adult patients.[6] In addition, BP has also been shown to be associated with Coombs'-positive hemolytic anemia, membranous glomerulonephritis, ulcerative colitis, and hyperimmunoglobulin E syndrome and to develop after liver transplantation.[78]

The diagnosis of BP is usually established by a combination of clinical history, histopathologic features of the disease, and immunofluorescence examination. BP mostly presents as multiple tense bullae. Histopathologic examination of BP mostly reveals eosinophilic infiltration and subepidermal bullae. DIF test of perilesional skin samples commonly indicates linear deposition of IgG and C3 in the basal membrane.[18]

Systemic corticosteroids such as prednisone (1–2 mg/kg/day) constitute the mainstay treatment of pediatric BP.[3] BP commonly yields good prognosis. Patients respond well to early treatment, and most of them achieve complete remission within a few months from the initiation of therapy. Recurrence rarely occurs after the termination of corticosteroid therapy.[1] In resistant cases, some other drugs including dapsone, azathioprine, cyclosporine, mycophenolate mofetil, rituximab, and intravenous immunoglobulin can also be used.[123]

Metamizole, also known as dipyrone, is a nonsteroidal anti-inflammatory drug commonly used as an analgesic or antipyretic agent.[9] Commonly reported side effects of metamizole include agranulocytosis, anemia, acute kidney failure, and severe thrombocytopenia. The cutaneous side effects of metamizole include diaphoresis, urticaria, angioedema, morbilliform, erythematous and purpuric rash, fixed drug eruption, DRESS syndrome, acute generalized exanthematous pustulosis, and toxic epidermal necrolysis.[9] Brenner et al. reported three cases of pemphigus vulgaris induced by metamizole.[10]

Clinicians should be aware of this side effect of metamizole which is a common drug used in clinical practice.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.