Mirjana Gajić-Veljić

Granulomatosis with Polyangiitis (Wegener's Granulomatosis) in Children: Report of Three Cases with Cutaneous Manifestations and Literature Review

Granulomatosis with polyangiitis (GPA), also known as Wegeners granulomatosis, is a rare disease in childhood. Of 39 GPA patients that we diagnosed during a 20‐year period, only 3 (7.7%) were younger than 18 years. We report the course of GPA in three girls whose disease started at the ages of 16, 11, and 6 years. All had cutaneous manifestations: the first had necrotizing vasculitis, the second had palpable purpura, and the third had right upper‐eyelid edema and infiltration and proptosis caused by extraocular pseudotumor, initially histologically misdiagnosed as orbital immunoglobulin G4 (IgG4)‐related disease. Unlike with skin vasculitis and glomerulonephritis, upper‐airway and orbital inflammation were resistant to immunosuppressive therapy. Our report emphasizes that children presenting with cutaneous vasculitis, chronic eyelid swelling, sinusitis, or hoarseness should be tested for antineutrophil cytoplasmic antibodies. We emphasize that the upper‐eyelid edema and infiltration, with histologic characteristics of orbital IgG4‐related disease, may be the initial presentation of localized GPA in children, a feature that, until now, has been described only in adults.

Combined oral pulse and topical corticosteroid therapy for severe alopecia areata in children: a long-term follow-up study.

There are no widely accepted therapy protocols for severe alopecia areata (AA). We treated 65 children/adolescents with AA affecting >30% of scalp. Fourty‐three percent of patients had AA plurifocalis (AAP). Fifty‐seven percent had AA subtotalis (AAS), AAP+ophiasis (AAP+OPH), and alopecia totalis/universalis (AT/AU). Long‐term follow‐up (median 96 months) data were available for 69% of patients. Oral dexamethasone (prednisolone 5 mg/kg equivalent) was given once in 4 weeks. Patients received 6, 9, or 12 pulses. Clobetasol propionate 0.05% ointment under plastic wrap occlusion was applied 6 days a week. Hair growth was assessed on a scale ranging 0–100% of regrowth in individual AA lesions. Regrowth >50% was considered good response. Six to twelve months months after the therapy, 56.9% of patients had >75% of hair regrowth. In AAP, 65.5% had complete regrowth. 61.5% of all patients were considered good responders. Significantly, higher percentage of good responders was found in AA lasting ≤12 months. No patients had serious side effects. There was no change in stability of the hair status at the long‐term follow‐up. Most AA patients had beneficial effects with this protocol. Best results were in AAP and AAP+OPH. Combined topical and oral pulse corticosteroid therapy of AA in children shows long‐lasting results, without serious side effects.

Stevens–Johnson syndrome and toxic epidermal necrolysis: a 20‐year single‐center experience

Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life‐threatening diseases that are most frequently caused by drugs.

Prepubertal onset of hidradenitis suppurativa in a girl: A case report and literature review

1. Louhichi N, Hadjsalem I, Marrakchi S, Trabelsi F, Masmoudi A, Turki H, et al. Congenital lamellar ichthyosis in Tunisia is caused by a founder nonsense mutation in the TGM1 gene. Mol Biol Rep 2013;40:2527-32. 2. Huber M, Yee VC, Burri N, Vikerfors E, Lavrijsen AP, Paller AS, et al. Consequences of seven novel mutations on the expression and structure of keratinocyte transglutaminase. J Biol Chem 1997;272:21018-26. 3. Terrinoni A, Serra V, Codispoti A, Talamonti E, Bui L, Palombo R, et al. Novel transglutaminase 1 mutations in patients affected by lamellar ichthyosis. Cell Death Dis 2012;3:e416. 4. Nakagawa N, Yamamoto M, Imai Y, Sakaguchi Y, Takizawa T, Ohta N, et al. Knocking-in the R142C mutation in transglutaminase 1 disrupts the stratum corneum barrier and postnatal survival of mice. J Dermatol Sci 2012;65:196-206. 5. Vahlquist A, Ganemo A, Virtanen M. Congenital ichthyosis: An overview of current and emerging therapies. Acta Derm Venereol 2008;88:4-14.

Importance of low serum DNase I activity and polyspecific anti-neutrophil cytoplasmic antibodies in propylthiouracil-induced lupus-like syndrome

OBJECTIVE To study the role of deoxyribonuclease (DNase) I activity and ANCA in propylthiouracil (PTU)-induced lupus-like syndrome (LLS). METHODS We compared 36 SLE patients with 17 PTU-induced LLS patients diagnosed from 2008 to 2014. We studied ANCA profile (MPO, PR3, lactoferrin, CTG, elastase, bactericidal/permeability-increasing protein), anti-dsDNA, anti-ENA, anti-nucleosome, anti-histone, anti-C1q, anti-aCL, complement components, cryoglobulins and serum DNase I activity. Healthy persons and patients without LLS treated with PTU comprised the control groups. Twelve LLS patients were serologically and clinically followed for 4.1 (S.D. 2.0) years. RESULTS PTU-induced LLS patients less frequently had arthritis, renal and neurological manifestations, but more frequently had fever, purpura, urticarial-like vasculitis and ulceration (P < 0.01). PTU-induced LLS patients more frequently had polyspecific ANCA (anti-MPO, anti-elastase and anti-PR3 were most commonly detected) (P < 0.01). SLE patients more frequently had anti-dsDNA, anti-ENA, anti-nucleosome, anti-C1q (P < 0.01) and anti-histone antibodies (P < 0.05). PTU-induced LLS patients had lower DNase I activity than SLE patients and controls (P < 0.01). Discontinuation of PTU increased DNase I activity, although it did not reach the levels of controls (P < 0.01). After remission, MPO-ANCA decreased (P < 0.01), but persisted for a long time. CONCLUSION PTU, as a trigger, and low DNase I activity, as a predisposing factor, may lead to LLS. Polyspecific ANCAs are useful markers for differentiating SLE from PTU-induced LLS. Low DNase I activity might be an important prognostic biomarker for PTU-induced LLS. Monitoring of ANCA and DNase I activity may prevent long-lasting exposure to causal drugs, unnecessary immunosuppressive therapy and severe complications of LLS.

National Guidelines for the Treatment of Atopic Dermatitis

1Clinic of Dermatovenereology, Clinical Center of Serbia, Department of Dermatovenereology, School of Medicine, University of Belgrade, Belgrade, Serbia 2Institute for Child and Youth Health Care of Vojvodina, Faculty of Medicine, University of Novi Sad, Serbia 3Clinic of Skin and Venereal Diseases, Military Medical Academy, Department of Dermatovenereology, School of Medicine, University of Belgrade, Belgrade, Serbia 4Department of Dermatovenereology, Clinic of Skin and Venereal Diseases, Clinical Center Niš, School of Medicine, University of Niš, Niš, Serbia

Pachyonychia Congenita - Can a Specific Phenotype be a Clue to a Genetic Defect? - a Case Report and Literature Review

Abstract Pachyonychia congenita (PC) is a rare inherited disorder of keratinization characterized by hypertrophic nail dystrophy, painful palmoplantar blisters, cysts, follicular hyperkeratosis and oral leukokeratosis. These pathological clinical features are resulting from mutations in keratin proteins including KRT6A, KRT6B, KRT6C, KRT16, and KRT17. We present a 6-year-old girl with hypertrophic nail dystrophy, follicular hyperkeratosis, circumscribed plantar keratoderma and oral leukokeratosis. The features were consistent with the diagnosis of PC. The patient has been registered in the International Pachyonychia Congenita Research Registry (IPCRR) and is waiting for a detailed genetic analysis. The IPCRR has contributed to publication of numerous papers which emphasized the importance of the mutation type affecting various clinical presentations of PC. Based on recent data, a new classification system has been developed for PC, and it is gradually replacing the earlier classifications. It is based almost exclusively on the mutated genes. In this report we have raised the hypothesis that distinctive clinical features may be highly suggestive of a specific keratin mutation.

Diffuse Cutaneous Mastocytosis in a Child - a Case Report

Abstract Mastocytosis refers to a group of diseases characterized by a clonal proliferation and accumulation of mast cells in one or more tissues/organs with different clinical presentations. In children, limited cutaneous forms of mastocytosis are rather frequent, while systemic mastocytosis is rare. The diagnosis of cutaneous mastocytosis is based on clinical findings and histopathology. We present a patient who developed skin lesions at the age of 18 months. Clinical findings, confirmed by histopathology, were consistent with diffuse cutaneous mastocytosis. The follow-up period was 7 years. The treatment included oral antihistamines in combination with mast cell stabilizers, mild topical steroids and avoidance of friction. During the follow-up period, there were no signs of systemic involvement, and the quality of life was preserved, despite the large surface of affected skin. This case report should increase the awareness and knowledge of clinicians about this rare form of cutaneous mastocytosis in the pediatric population.

IgA Pemphigus in a Child – a Case Report

Abstract IgA pemphigus (IGAP) is a rare autoimmune bullous disease characterized by IgA deposits on keratinocyte cell surfaces. The IGAP is classified into: 1) subcorneal pustular dermatosis (SPD) type, and 2) intraepidermal neutrophilic (IEN) IgA dermatosis type. So far, only 9 children with IGAP have been described in the literature, of whom only 3 with SPD type. We report a 3-year-old boy with SPD type of IGAP. Clinically, he presented with pruritic vesicles, pustules and erosions on the face, trunk, groin area, and extremities. Histopathology showed subcorneal pustules containing a few acantholytic cells. Direct immunofluorescence (DIF) test of Tzanck smear showed intercellular IgA deposits on the surface of the groups of epidermal cells. Oral dapsone and prednisone induced remission after two weeks; the treatment was discontinued 11 months later, and complete remission was achieved during 19 months without any treatment. Direct immunofluorescence of Tzanck smear is a simple, sensitive, rapid and non-aggressive test, very suitable for the diagnosis of IGAP in children.

Orofacial granulomatosis in a 12-year-old girl successfully treated with intravenous pulse corticosteroid therapy and chloroquine

Orofacial granulomatosis, a rare disease in childhood, is characterized by orofacial swelling in the absence of systemic disease. We report the case of a 12‐year‐old girl with asymptomatic erythematous infiltration of her upper lip, cheeks, and chin that had persisted for more than 2 years; biopsy confirmed granuloma formation. Because a large area was affected, intralesional corticosteroids were inappropriate and six cycles of 3‐day intravenous pulse corticosteroid therapy (dexamethasone 1.5mg/kg), repeated once after 4 weeks, was given. Our patient also received oral chloroquine and topical emollients. At the end of the sixth pulse cycle, the infiltration had completely resolved, leaving slight residual erythema.