Svetlana Popadić

Bullous Pemphigoid Induced by Penicillamine in a Patient with Wilson Disease

We report a 47-year-old man with Wilson disease who developed bullous lesions on the trunk and extremities after 20 years of penicillamine treatment. The histologic and immunofluorescence findings were diagnostic of bullous pemphigoid. When penicillamine was replaced by zinc sulfate, the patient’s bullous skin lesions improved rapidly. However, after 2 months of zinc sulfate treatment, the patient’s skin condition remained improved but his neurologic disease became worse and penicillamine was reinstituted. Bullous lesions recurred within 1 week and the diagnosis of penicillamine-induced bullous pemphigoid was confirmed. This is the first report of penicillamine-induced bullous pemphigoid in a patient with Wilson disease.

Congenital self-healing histiocytosis presenting as blueberry muffin baby: a case report and literature review.

Congenital self-healing Langerhans cell histiocytosis (CSHLCH), also called as Hashimoto-Pritzker disease, is a rare, benign variant of histiocytosis. Despite the initial dramatic clinical presentation, affected infants are otherwise healthy and skin lesions disappear spontaneously within several weeks to months. We present a case of CSHLCH presenting as blueberry muffin baby. The lesions appeared in the first week of life and lasted 6 months. The follow-up period was 24 months, without any signs of relapse. At the pediatric dermatology unit of our clinic, during the last 20 years, we had 10 children with Langerhans cell histiocytosis and among them only one with CSHLCH. In the literature, we found only 5 newborns with Langerhans cell histiocytosis presenting as blueberry muffin baby, among them only 4 with self-healing CSHLCH. The early recognition of CSHLCH may spare children from redundant and potentially toxic systemic treatment.

Pemphigus vulgaris and pemphigus foliaceus determined by CD86 and CTLA4 polymorphisms

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are rare autoimmune blistering diseases with presumed T-cell-dependent pathology. Activation of naïve T cells is dependent on antigen recognition, subsequent signaling through the T-cell receptor complex (signal 1), and various other interactions of T cells with antigen presenting cells that may be collectively designated as signal 2, which is unconditionally required for T-cell activation both in response to infection and to autoantigens. Among the best described interactions contributing to signal 2 are those mediated by B7 family molecules, such as CD80 and CD86 with their ligands; CD28, providing activation signals; and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), conferring inhibition. Single nucleotide polymorphisms (SNPs) within genes encoding those molecules may alter the signaling process. It is not known whether functional genetic polymorphisms within genes encoding the aforementioned proteins may increase risk for developing PV and PF and, if so, whether they might serve as biomarkers for susceptibility to these diseases. To address those questions, we examined functional single nucleotide polymorphisms within CD86 (rs1129055) and CTLA4 (rs733618 and rs5742909) genes in 61 pemphigus patients and 486 healthy controls. We found statistically significant differences in allele and genotype frequencies between PV patients and controls for rs1129055, as well as for rs5742909 among PV and PF patients. Namely, the rs1129055 A allele was significantly more common in PV patients compared with controls (35.4% versus 25.7%, respectively; P = .040), whereas the rs5742909 T allele was significantly more common in PF compared with PV patients (19.2% versus 5.2%, respectively; P = .035). The frequency of the rs5742909 T allele did not, however, differ significantly in PF or in PV compared with controls (10.5%; P = .187 and P = .100, respectively). We report a novel association of SNPs within CD86 and CTLA4 genes with pemphigus. The CD86 rs1129055 A allele appears to confer susceptibility to PV but not to PF.

TNF, IL12B, and IFNG Gene Polymorphisms in Serbian Patients with Psoriasis

Background Psoriasis is a common chronic inflammatory skin disease with a strong genetic basis. Cytokines such as tumor necrosis factor alpha (TNF-α), interleukins (ILs) such are IL-12 and IL-23, and interferon gamma (IFN-γ) are released from various inflammatory and resident cells, and have been implicated in the initiation/maintenance of inflammation. Certain alleles of the aforementioned cytokines may be associated with disease susceptibility/severity. Objective To investigate the association of three common functional gene polymorphisms, namely TNF -308 G/A (rs1800629), IL12B (encoding the p40 subunit of IL-12/23) +1188 A/C (rs3212227), and IFNG +874 T/A (rs2430561) with psoriasis development and severity in Serbian patients. Methods We genotyped 130 patients with psoriasis (26 of whom also had psoriatic arthritis) and 259 controls; rs1800629 and rs3212227, and rs2430561, by real-time PCR assay. Results The TNF GG genotype was detected at a higher frequency in patients with psoriasis compared to control subjects (OR, 1.420; 95% CI, 0.870~2.403) without statistical significance (p=0.191). Lack of the TNF G allele was associated with lower psoriasis severity (p=0.007). The IL12B AC genotype was underrepresented in the patients with psoriatic arthritis compared to healthy subjects (OR, 0.308; 95% CI, 0.090~1.057; p=0.049). The distribution of the rs2430561 allele and genotype frequencies was similar between patients with psoriasis and controls. Conclusion Our study demonstrates an effect of the rs1800629 on psoriasis severity, and a marginal impact of the rs3212227 on susceptibility to psoriatic arthritis. Collectively, our results obtained in a Serbian cohort expand current knowledge regarding individual predisposition to psoriatic disease.

Incidence of autoimmune bullous diseases in Serbia: a 20-year retrospective study.

While most previous surveys on the clinico‐epidemiological features of autoimmune bullous diseases (AIBDs) have predominantly focused on a single disease entity or just one disease group, there have been only few studies examining the incidence of various AIBDs. In the present study, we set out to determine the spectrum of AIBDs, to estimate the incidence of the most common AIBDs, and to examine their temporal trends in Central Serbia over a period of 20 years.

Direct immunofluorescence of the outer root sheath in anagen and telogen hair in pemphigus vulgaris and pemphigus foliaceus.

Direct immunofluorescence of peri‐lesional skin is the gold standard in the diagnosis of pemphigus. A specific immunofluorescence pattern may also be demonstrated in the outer root sheath of anagen and telogen hair. We demonstrated an intercellular reticular deposition of immunoglobulin G in the outer root sheath of plucked anagen and telogen hair in all pemphigus vulgaris patients with active disease and for the first time in all patients with active pemphigus foliaceus. Moreover, we demonstrated for the first time that plucked hair samples may be kept at −20°C for at least 2 weeks before immunofluorescent staining and analysis.

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

Inzidenz von bullösen Autoimmunerkrankungen in Serbien: eine retrospektive Studie über 20 Jahre

Die meisten früheren Arbeiten zu den klinisch‐epidemiologischen Merkmalen von bullösen Autoimmunerkrankungen (AIBD) konzentrierten sich vor allem auf eine einzige Krankheitsentität oder nur eine Krankheitsgruppe; nur in wenigen Studien wurde die Inzidenz verschiedener AIBD untersucht. Bei der vorliegenden Studie war es unser Ziel, das gesamte Spektrum der AIBD zu betrachten, die Inzidenz der häufigsten AIBD zu ermitteln und die zeitlichen Trends ihres Auftretens in Zentralserbien über einen Zeitraum von 20 Jahren zu untersuchen.

Pemphigus vulgaris in three adolescents: The course of the disease

We report three adolescents with pemphigus vulgaris whose disease started at the age of 13, 15 and 14 years, respectively. The course of the disease and the treatment approaches were reviewed. Pemphigus vulgaris during childhood and adolescence is a very rare disease in this part of Europe. Among 410 pemphigus vulgaris patients that we treated during the 20‐year period, only three patients (0.73%) were under the age of 18 years. According to our experience, the course of pemphigus vulgaris in patients before the age of 18 years is comparable with the course of pemphigus vulgaris in adults.

Granulomatous rosacea: Like leukemid in a patient with acute myeloid leukemia

INTRODUCTION Skin findings in leukemias may be divided into specific lesions (leukemia cutis) and non-specific lesions (leukemids) which may be found in up to 80% of all patients with leukemias. The leukemids vary clinically and they are usually a manifestation of bone marrow or immunologic impairment, but also Sweet syndrome, pyoderma gangrenosum, erythroderma, maculopapular exanthema, prurigo-like papules, generalized pigmentation, follicular mucinosis, generalized pruritus may be found during the course of leukemia. CASE REPORT We report a 70-year-old male with a 3-month history of erythema, papules and pustules on the face, ears and neck and over a month history of refractory anemia, anorexia, weight loss, malaise, and fever. Physical examination revealed symmetric erythematous, violaceous papules, papulo-nodules and plaques with slate scale and sparse, small pustules on the face, earlobes and neck. Histopathologic findings of involved skin showed diffuse mixed inflammatory cell infiltrate with perifollicular accentuation and focal granulomatous inflammation in the papillary and upper reticular dermis. Extensive checkup revealed the presence of acute myeloid leukemia French-American-British (FAB) classification subtype M2, with signs of three-lineage dysplasia. The patient was treated by L6 protocol which led to complete remission, both in bone marrow and skin, but after seven months he had relapse of leukemia with the fatal outcome. CONCLUSION This case indicates the importance of skin eruptions in the context of hematological malignancies.