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Revista chilena de pediatría

versión impresa ISSN 0370-4106

Rev. chil. pediatr. vol.89 no.5 Santiago oct. 2018

http://dx.doi.org/10.4067/S0370-41062018005000708 

CLINICAL CASE

Pemphigus vulgaris in pediatrics: A case report

Ana Laura Casuriaga Lamboglia1 

Agustina Minut Gubitosi2 

Claudia Guebenlián Bakerdjian3 

Gustavo Giachetto Larraz1 

1 Pediatrician. Spanish Association, Montevideo, Uruguay.

2 Former resident of Pediatrics, Spanish Association. Montevideo, Uruguay.

3 Dermatologist. Spanish Association. Montevideo, Uruguay.

Abstract:

Introduction:

pemphigus vulgaris is a serious and infrequent disease in children. Its timely diagnosis and treatment allows modifying its prognosis. The objective is to describe its clinical characteristics, and the diagnostic and therapeutic approach of this uncommon autoimmune blistering disease in children.

Clinical case:

2-year-old male patient, previously healthy. He initially presented generalized dermatosis with maximum lesion areas at the umbilical region, limbs and genitals; characterized by blisters, some denuded, and of easy bleeding, without mucosal involvement nor fever. Bullous im petigo was diagnosed and topical and systemic antibiotic treatment was started, showing no clinical improvement. He developed extension of the lesions with oral and anal mucosal involvement. The histologic and direct immunofluorescent study of lesions and perilesional skin confirm the diagnosis of pemphigus vulgaris. The patient started treatment with corticosteroids and immunomodulatory agents with good clinical response.

Conclusions:

Due to the similarity with other more prevalent infectious and inflammatory diseases, a high index of suspicion is required in order to avoid delays in the diagnosis and the start of treatment. In patients with blisters with an unexpected clinical evolu tion, it is necessary to conduct a joint evaluation with a dermatologist and to assess the opportunity of performing a biopsy of the lesion and perilesional skin for histological study and direct immunofluo rescence, which will allow diagnostic confirmation.

Keywords: Blistering diseases; pemphigus vulgaris; pediatrics

Introduction

Acquired blistering diseases in children are a diag nostic challenge due to the etiological heterogeneity and its clinical manifestations. According to the etio-pathogenic mechanism they are classified as infectious, inflammatory, and secondary to physical and autoim mune agents1-3. The awareness of its distinctive characteristics allows an adequate diagnostic approach and a timely treatment, which influences the prognosis1-3.

Acquired autoimmune forms are uncommon in children. From the histopathological point of view, two types are distinguished: the intraepidermal and the subepidermal. Pemphigus vulgaris is an intraepi dermal blistering disease. Other intraepidermal forms include pemphigus foliaceus, immunoglobulin A (IgA) pemphigus, and paraneoplastic pemphigus2,3. According to their age of appearance, they are classi fied as congenital and acquired. The acquired ones are sub-classified in infectious, inflammatory, secondary to physical and autoimmune agents3-6.

Pemphigus vulgaris (PV) is a chronic, rare and se vere autoimmune blistering disease with cutaneous- mucosal involvement. Its incidence is estimated at 0.1 0.5% of cases per 100,000 people per year. It is exceptional in children4,7,9-13. It is characterized by the ap pearance of superficial thin-walled blisters on healthy skin and/or mucosa, which extend progressively and rupture easily, leaving large exposed areas. Nikolsky sign, this is to say the epidermal detachment caused by a firm linear pressure on normal skin, is characteristic but not pathognomonic. The peripheral increase of the blister size when pressing it vertically or Asboe-Hansen sign is another possible manifestation(3>14-18).

Skin lesions predominate in the urogenital, palpe bral, anus, hands, face, neck, thorax and feet. In more than 60% of cases, the disease begins in the oral cavity with involvement of the palate, gums and occlusal plane. The nasal and conjunctival mucous membranes are frequently affected7,8,12.

Patients with PV usually present a significant de terioration of the general condition secondary to extensive cutaneous/mucosal involvement, difficulty in the fluids and food intake, and protein and electroly te losses. Local and systemic infectious complications are common due to the loss of skin integrity and the immunosuppressive effects of the drugs used in its treatment7,11-14.

Diagnosis in children is often difficult due to the low prevalence of the disease and the wide variety of differential diagnoses. Its confirmation requires a biopsy3,7-9.

The objective of this study is to describe the cli nical characteristics of a 2-year-old child with PV, an uncommon form of autoimmune blistering disease in children, and to review its diagnostic and therapeutic approach.

Clinical case

A previously healthy 2-year-old boy who consulted due to the sudden and progressive appearance of blisters in the umbilical region, upper and lower limbs and genitals, some of which were denuded with easy blee ding, without mucosal involvement or fever (Figure 1). Bullous impetigo was diagnosed and treated with oral administration of trimethoprim-sulfamethoxazole was started. On the tenth day of treatment, there was no improvement and, in addition, small erosions appea red in the oral mucosa. In the lesions exudate culture, he developed methicillin-sensitive Staphylococcus au reus, therefore it was indicated cefradine through oral route for 10 days.

Figure 1 Blister lesions evolved denudated. 

At one month of follow-up, new blistering lesions appeared on the face, trunk, limbs and genitals, intensely painful erosions on the anal mucosa, and greater oral mucosa involvement with multiple erosions that made feeding difficult; he also presented dysphonia. The examination showed crusted lesions on lips with positive Nikolsky sign (Figures 2 and 3). Probable to xicodermia, Stevens-Johnson Syndrome type was suggested, laboratory tests were requested: hemogram, C-reactive protein, liver tests, and renal function that did not show alterations. There was no bacterial deve lopment in the blood culture. The serology for human immunodeficiency virus was negative, and the study of lymphocyte populations and immunoglobulin levels were normal.

Figure 2 Crusted lesions on lips. 

Figure 3 Extensive blister lesions on the back, positive Nicolsky sign. 

The patient was referred to a dermatologist, where a lesional and perilesional skin biopsy was performed. The histology with hematoxylin and eosin staining showed a vesicular lesion, with suprabasal blister and persistence of basal cells attached to the basal layer (row of tombstone image). Necrobiotic tissue and fibrinous exudates comprising acantholytic cells were observed in the top of the blister and lymphomono- nuclear infiltrates in the dermis with frequent eosino phils. Direct immunofluorescence (DIF) showed linear intraepidermal intercellular fluorescent deposition of Immunoglobulin G (IgG) and complement fraction C3. According to the findings of the immunofluores cence biopsy, the diagnosis of PV was made.

Prednisolone through oral route was initiated at 1.5 mg/kg/day with fast improvement of lesions (Figures 4 and 5). After one month he relapsed, therefore azathio- prine was added at 3 mg/kg/day through the oral route. The patient received both drugs for three months, then they were progressively decreasing until the suspension one year after starting the treatment. After five months without treatment, he had a mild relapse that led to a restart of prednisolone and azathioprine. In the last follow-up visit, two years after the debut of the PV, the patient was four years old, asymptomatic and in a plan of progressive decrease of the medication.

Figures 4 and 5. Appea rance of the lesions 72 hours after the start of treatment with corticos teroids. 

Discussion

PV is a rare disease in children. In 1955, the first case in pediatric age was reported. Since then, approximately 50 new cases have been reported to date3,8.

PV is an autoimmune disease characterized by the production of autoantibodies against specific proteins of the skin and mucous membranes, which causes the separation between keratinocytes or acantholysis. The rupture of intercellular junctions is mediated by IgG antibodies which act against desmoglein-3, affecting the structure of desmosomes14. Genetic and environ mental factors have been associated in its etiopathogenesis. An association between PV and certain antigens of the major histocompatibility complexes class II has been observed. Drugs, hormones, physical agents (ra diation and burns) and some viruses (Epstein Barr, Cytomegalovirus, Herpesvirus 8) have been associated with probable immune stimuli(4,7, 13-18).

In this case, the definitive diagnosis was established after one month of illness. It is possible that the wide variety of blistering diseases most prevalent at this age and the lack of knowledge of this entity explain the diagnosis delay. The initial characteristics of the skin lesions and the absence of mucosal and systemic involvement led to the approach of bullous impetigo. However, two elements should have warned of differential diagnoses. On the one hand, the lack of impro vement with an adequate empirical antibiotic therapy, and on the other hand, the appearance of lesions in the oral mucosa, since bullous impetigo does not describe mucosal involvement19. The finding of Staphylococcus aureus in the exudate of lesions must have been inter preted as a possible contaminant. It was a strain sus ceptible to methicillin and therefore also susceptible to trimethoprim-sulfamethoxazole. It is important to interpret the results of laboratory tests in relation to the evolution of clinical manifestations.

Subsequently, when mucosal involvement was extended and in addition to the general condition involvement, probable toxicodermia of the Stevens- Johnson Syndrome type was raised. The diagnosis of toxicodermia is clinical and exclusionary. In this case, the suspicion was based on the history of exposure to drugs recognized as causative agents, such as sulfona mides and cephalosporins. However, the characteris tics of the lesions and the absence of fever distanced this diagnostic approach. In Stevens-Johnson Syndro me, the eruption begins with maculopapular erythe matous lesions that in their evolution present purple coloration and then become blisters. That was not the evolution in the patient20.

It is highlighted that although the clinical manifes tations of autoimmune blistering diseases in children are similar to those of adults, the low prevalence of this disease in children causes delays in diagnosis due to the lack of sensitization and therefore clinical suspicion. In addition, in their initial phases, these autoimmune dermatoses can mimic other more common processes in the pediatric age, such as occurred in the analyzed case8.

The diagnosis of PV requires biopsy as it is con firmed by histological study and direct immunofluorescence. The histopathological study is characterized by the presence of intraepidermal blisters containing eosinophils and perivascular superficial and deep in flammatory infiltrates. Direct immunofluorescence (DIF) generally reveals linear intraepidermal interce llular IgG and C3 depositions.

Indirect immunofluorescence (IFI) uses patient serum to demonstrate the presence of circulating antibodies against a hemidesmosome antigen that are pre sent in 70% of cases. The skin biopsies should include the edge of the ampulla or integral vesicle to observe the level of formation of the lesion with hematoxylin and eosin staining and that in this pathology acquires the characteristic aspect of a row of tombstones. For DIF, a sample of the perilesional skin adjacent to the blister lesions will be obtained4,7,11,12.

Regarding treatment, the use of systemic steroids has changed the prognosis of the disease. Before its use, the mortality was close to 75% and then it was reduced to figures close to 6%4,14,18,21.

Prolonged corticosteroid treatment is usually re quired thus side effects are very common. This has encouraged the search for adjuvant treatments with immunomodulators in order to reduce the dose and duration of corticosteroids. There is little scienti fic evidence on the comparative efficacy of different immunomodulators. Despite this, good results have been reported with the use of azathioprine in children10,14,18,22.

Patients with mild and moderate forms who have a fast response to treatment are more likely to achieve complete remission. Suspension of treatment is based on prolonged clinical remission and IFI findings(5,7, 8,14,18). In the long term, better results have been repor ted in children than in adults, as long as treatment is started early or promptly4.

The importance of long-term follow-up of patients is highlighted in order to monitor the evolution of the disease, the adverse effects of the indicated treatments as well as the progressive reduction of the drugs to the minimum doses sufficient to keep the patient asymptomatic7.

Conclusions

Pemphigus vulgaris is a severe autoimmune blis tering disease, rare in pediatrics, therefore its diagno sis requires a high rate of suspicion to avoid delay in treatment and improve prognosis. Given the similarity with other exanthematic diseases of higher prevalence, it is necessary when there are diagnostic doubts in cases of unexpected evolution, re-evaluate the clinical mani festations with the specialist and perform lesional and perilesional skin biopsy with histological study and direct immunofluorescence to confirm the diagnosis.

It is important to report new cases of pemphigus vulgaris in children in order to characterize their behavior and response to treatment in this age.

Ethical Responsibilities

Human Beings and animals protection: Disclosure the authors state that the procedures were followed according to the Declaration of Helsinki and the World

Medical Association regarding human experimenta tion developed for the medical community.

Data confidentiality: The authors state that they have followed the protocols of their Center and Local regulations on the publication of patient data.

Rights to privacy and informed consent: The authors have obtained the informed consent of the patients and/or subjects referred to in the article. This docu ment is in the possession of the correspondence author.

Financial Disclosure: Authors state that no economic support has been asso ciated with the present study.

Conflicts of Interest: Authors declare no conflict of interest regarding the present study.

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Received: May 02, 2018; Accepted: July 02, 2018

Correspondence: Ana Laura Casuriaga Lamboglia. E-mail: anitacasuriaga7@gmail.com.

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