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Introduction. Mucous membrane pemphigoid (MMP) is a rare autoimmune, chronic inflammatory disease that affects mucous membranes, most commonly the eyes and mouth, with or without skin involvement. It is a complex disease with several complications, including scarring, especially on conjunctival mucosa, that can lead to visual loss. Case report. We report four patients (two men and two women) with MMP. In all patients, the disease started between seventy and eighty years of age. The diagnosis was confirmed based on clinical appearance, histology, direct and indirect immunofluorescence studies, indirect split skin technique, and enzyme-linked immunosorbent assay (ELISA) test. The majority of lesions were on the gums and buccal mucosa; one patient had laryngeal involvement and a lesion on the umbilicus. No ocular involvement and no malignancy were detected. Direct immunofluorescence tests revealed continuous linear IgG deposition in the basal membrane zone in two patients, and they were treated with oral nicotinamide and tetracycline hydrochloride. In two patients, we detected IgG along with IgA linear deposition; they received treatment with methylprednisolone. Complete remission was achieved in all patients. Conclusion. Early diagnosis and an adequate therapeutic approach are necessary for the MMP treatment in long-term disease control and reduction of disease-related complications.

Introduction. Wells` syndrome (eosinophilic cellulitis) is a chronic, recurrent disease characterized by episodes of erythematous and edematous plaques or nodules with occasional development of hemorrhagic bullae on the trunk and limbs. Eosinophilic granulomatosis with polyangiitis, formerly known as Churg-Strauss syndrome, is a specific variant of the group of diseases characterized by necrotizing vasculitis of small to medium-sized blood vessels affecting multiple organ systems. The association of Wells` syndrome and eosinophilic granulomatosis with polyangiitis is very rare, and to our knowledge has been reported in only ten patients. Case report. We present a case of a 34-year-old woman with a 3-year history of periodical onset of erythematous plaques on the trunk and edematous plaques clinically resembling cellulitis on her lower limbs. The patient reported a one-year history of asthma, rhinosinusitis, and nasal polyposis. Skin biopsy revealed the presence of diffuse eosinophilic infiltrates in the dermis accompanied by characteristic “flame figures”. Further investigation showed peripheral blood eo-sinophilia (22.6%), bilateral maxillary sinusitis, presence of eosinophil infiltrates and microabscesses in the bron-chial wall, and pericapillary eosinophil infiltrates in the pulmonary interstitium shown by bronchoscopy and transbronchial biopsy, respectively. Treatment was started with methylprednisolone 0.5 mg/kg/day, and the dose was gradually tapered for the following twelve weeks. Complete remission of skin changes was achieved, but new lesions appeared in the past two years, which required repeated treatment. Conclusion. Association of these syndromes is unusual and may be based on the common pathogenetic background. We hypothesize that Wells` syndrome could be a stage preceding eosinophilic granulomatosis with polyangiitis, and that patients should be evaluated for eosinophilic granulomatosis with polyangiitis, since these two diseases overlap in clinical and laboratory findings.

Background/Aim. Psoriasis as multisystemic inflammatory dis-ease is related with an increased cardiometabolic risk. The aim of the study was to analyze risk biomarkers, peripheral and renal arteries ultrasonography and echocardiography for subclinical atherosclerosis and metabolic disease in 106 subjects (66 psoriasis patients and 40 controls, 20 eczema patients and 20 healthy volunteers). Methods. In all exameenes following parameters were analyzed: body mass index (BMI), C-reactive protein, D-dimer, serum amyloid A (SAA), apolipoprotein (Apo) A1, ApoB, ApoB/Apo A1 index, fasting glucose, C-peptide, fasting insulinemia, homeostatic model assessment-insulin resistance (HOMA-IR), HOMA-β-cell, lipid profile, serum uric acid concentration (SUAC), 24-h proteinuria and microalbuminuria. Carotid, brachial, femoral and renal arteries ultrasonography, as well as echocardiography was also performed. Results. Five of 66 (7.6%) psoriasis patients had metabolic syndrome (not present in both control groups). The following variables were increased in patients with psoriasis compared to both control groups: BMI (p = 0.012), insulinemia (p < 0.001), HOMA-IR (p = 0.003), HOMA-β cell (p < 0.001), SUAC (p = 0.006), ApoB/ApoA1 ra-tio (p = 0.006) and microalbuminuria (p < 0.001). Also, increased C-peptide (p = 0.034), D-dimer (p = 0.029), triglycerides (p = 0.044), SAA (p = 0.005) and decreased ApoA1 (p = 0.014) were found in the psoriasis patients compared to healthy controls. HDL cholesterol was decreased in the psoriasis patients compared to the control group of eczema patients (p = 0.004). Common carotid (CIMT) and femoral artery intima-media thickness (FIMT) was significantly greater (p < 0.001) and the maximal flow speed (cm/s) in brachial artery significantly de-creased (p = 0.017) in the patients with psoriasis in comparison to both control groups. In multivariate logistic regression analysis, after the adjustment for confounding variables, the most important predictor of CIMT and FIMT was the diagnosis of psoriasis (p < 0.001). Conclusion. Cardiometabolic risk biomarkers and ultrasonographic signs of early atherosclerosis are correlated with the diagnosis of psoriasis, and not to generalized eczema. Psoriasis was found to be an independent risk factor for subclinical atherosclerosis.

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Background/Aim. Treatment options for metastatic melanoma in Serbia are limited due to the lack of newly approved biologic agents and the lack of clinical studies. Also, there is a paucity of data regarding the treatment approaches in different tertiary centers and efficacy of available chemotherapy protocols. The aim of this study was to obtain more detailed data about treatment protocols in Serbia based on structured survey in tertiary oncology centers. Methods. Data about the melanoma patients treated in 2011 were analyzed from hospital databases in 6 referent oncology centers in Serbia, based on the structured survey, with the focus on metastatic melanoma patients (unresectable stage IIIC and IV). Results. A total of 986 (79-315 in different centers) patients were treated, with 320 (32.45%) newly diagnosed patients. There were 317 patients in stage IIIC/IV, 77/317 aged < 50 years. At the time of diagnosis 47.3% of patients were < 60 years of age (24.2% < 40 years, 23% 50-59 years, 52.6% > 60 years). At initial diagnosis 12.5% of patients were in stage III and 4.5% in stage IV. The most common type was superficial spreading melanoma (50-66%), followed by nodular melanoma (23.5-50%). Apart from the regional and distant lymph node metastases, the most frequent organs involved in stage IV disease were distant skin and soft tissues (12-55%), lungs (19-55.5%), liver (10-60%), and bones (3-10%). The first line therapy in stage IV metastatic melanoma was dacarbazine (DTIC) dimethyl-triazeno-imidozole-carboxamide in 61-93% of the patients, while the second line varied between the centers. Disease control (complete response + partial response + stable disease) was achieved in 25.7% of the patients treated with the first line chemotherapy and 23.1% of the patients treated with the second line therapy, but the duration of response was short, in first-line therapy 6.66 ± 3.36 months (median 6.75 months). More than 90% of patients were treated outside the clinical trials. Conclusion. Based on this survey, there is a large unmet need for the new treatment options for metastatic melanoma in Serbia. The development of national guidelines, and greater involvement in international clinical studies could lead to widening of treatment options for this chemotherapy resistant disease.

Introduction. Granulomatosis Wegener is anti-neutrophil cytoplasmic antibodies (ANCAs)-associated systemic vasculitis of unknown etiology. It is manifested as granulomatous necrotizing inflammation of the upper and lower parts of the respiratory tract, glomerulonephritis and systemic vasculitis involving most frequently the skin and oral mucous membrane. Sera markers of this disease are c-ANCA and p-ANCA. Case report. We presented a female patient aged 52 years with purpuric spots that had appeared on the lower legs ten months before admission to our hospital. The disease ran an aggressive course, and a month before admission hemorrhagic bullae, skin ulcers, hoarseness, dyspnea, generalized arthralgia, fatigue and fever had rapidly developed. Histopathological examination of a skin sample revealed necrotizing vasculitis, so that sera markers concentrations were elevated (c-ANCA, p-ANCA). There was a perforation of the nasal septum found on rhinoscopy. During hospitalization acute abdominal pain occurred, a possible tumor in the small intestine and possible granulomas in the liver were seen by multislice computed tomography (MSCT) examination, with normal findings on the lungs and kidneys. The treatment started with methylprednisolone: 500 mg/d i.v. infusion for consecutive 3 days, then 60 mg/d. On exploratory laparotomy small bowel perforation and diffuse peritonitis were found. Unstable in the postoperative period, the patient died on the day 12 of hospitalization. Conclusion. The reported patient was with fulminant Wegener’s granulomatosis, dominantly with skin changes and with gastrointestinal manifestation. This case accents the need for rapid systemic clinical evaluation in a severely ill patient with unclear diagnosis.

Introduction. Churg-Strauss syndrome (CSS) is an allergic granulomatous angiitis, a rare disease of small and medium arteries and veins, associated with the presence of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA). According to the American College of Rheumatology (ACR), there are four or more criteria out of six for the diagnosis: asthma, eosinophilia (> 10% in peripheral blood), paranasal sinusitis, pulmonary infiltrates, histological evidence of vasculitis with extravascular eosinophils, and mononeuritis multiplex or polyneuropathy. Case report. We reported a female patient, aged 80 years, with asthma for many decades and repeatedly verified eosinophilia in peripheral blood, in which CSS was suspected only after the occurrence of skin changes in the form of vesicles, vesiculopustule, purpuric macula, papule and petechiae. Further tests verified pulmonary infiltrates, paranasal sinusitis, extravascular eosinophils on histopathologic sample of skin tissue, and polyneuropathy. The treatment started with methylprednisolone (60 mg/d, with decreasing doses), and continued with pulse doses of cyclophosphamide (800 mg once monthly), also corticosteroid ointment for skin lesions. Conclusion. Despite long-standing pulmonary symptoms and laboratory findings of eosinophilia, the appearance of skin changes raised suspicion of possible CSS. Skin changes resolved and the patient was reffered to rheumatologist.

Background. Contact hypersensitivity (CHS) is a local inflammatory response of the skin following challenge of hapten-sensitized animals. It is the consequence of cell infiltration of derm and the release of inflammation mediators, among which Tumor necrosis factor-alpha (TNF-α) is one of the most important factors. The intensity of the inflammation could be quantified by ear swelling which is the classical manifestation of the reaction. This study was testing the working hypothesis that levels of TNF-α in skin organ culture medium should correlate with the intensity of CHS reaction measured in vivo by ear swelling assay, and with the density of dermal infiltrate in ear skin samples. In order to test the working hypothesis, the intensity of inflammatory reaction following challenge was evaluated by classical measurements of ear swelling, by the determination of TNF-α levels in culture fluids of ear skin following epicutaneous application of dinitrochlorobenzene (DNCB) into the ears of sensitized animals. Methods. Animal model of CHS reaction to DNCB in Albino Oxford rats was used as described. Ear swelling was quantified in percentage terms as the difference in thickness between the challenged and nontreated ears of the same animal. Dermal infiltrate density in histopathologically analyzed samples of ear skin was evaluated by computer-assisted image analysis. Ear skin samples were cultured in standard medium for 24 h, and TNF-α concentration in the conditioned medium was subsequently determined with ELISA test. Results. Dose-dependent increase in the density of the dermal infiltrate and in TNF-α in CM were noted following the application of 0.65%, 1.3% and 2.6% of DNCB to the ears of previously sensitized rats. The correlation between ear swelling and the levels of TNF-α (r=0.933, p

Background: Diagnosing mycosis fungoides (MF) can be challenging in the early stage of the disease because histopathological features may simulate a variety of benign inflammatory skin diseases. Assessment of T-cell clonality was found to be useful in diagnosis and follow-up of patients., Objective: In this study, PCR-based TCRgamma gene rearrangement analysis was performed in skin and peripheral blood samples of patients with MF treated at the two largest referral centers in Serbia, and the results obtained were correlated with clinical and follow-up data., Methods: Skin and peripheral blood samples were obtained with informed consent from 37 patients treated at the Department of Dermatology of the Military Medical Academy and the Medical Center of Serbia from 2001 to 2006. The median time of follow-up was 4 years. Multiplex PCR was used for TCRgamma gene rearrangement analysis in skin and peripheral blood samples. Clonality results were correlated with the clinical data and disease course data., Results: Monoclonality was detected in skin samples of 30/37 patients (81%), in 2/5 patients with large-plaque parapsoriasis (LPP), in 28/32 (88%) patients with histologically proven MF, and in 1/16 (6%) patients with benign inflammatory dermatoses. A monoclonal pattern in both skin and peripheral blood was detected in 7/16 (44%) patients in the late stage of the disease, and in 1/7 (14%) patients in the early stage of the disease. A dominant clone was found in both skin and peripheral blood in 1/4 patients in remission, 2/5 with a stable disease, and 4/9 (44%) with disease progression., Conclusion: TCR-gamma gene rearrangement analysis can be regarded as a useful adjunct to diagnosis of epidermotropic lymphoproliferative disorders. The presence of a dominant clone in both the skin and peripheral blood was more frequently detected in late stages and in patients with disease progression, confirming the usefulness of clonality detection by TCR-gamma gene rearrangement analysis in follow-up of patients with primary cutaneous T-cell lymphomas.