Serum Zinc Concentration in Patients with Alopecia Areata.

Alopecia areata is an autoimmune non-scarring disease in which the exact mechanism that induces loss of immune privilege is unknown. Zinc is important for DNA stability and repair mechanisms that are essential in maintaining normal hair growth. Zinc deficiency has been investigated as an important factor in many autoimmune diseases, and may have a possible role in the aetiopathogenesis of alopecia areata. This study included 32 patients with severe forms of alopecia areata, and 32 age- and sex-matched healthy controls. When comparing serum zinc levels in these 2 groups, statistically significantly lower zinc concentrations were found in the alopecia areata group (p = 0.017). Detected zinc deficiency was statistically more prevalent in patients with alopecia areata (p = 0.011). Evaluating patients with alopecia areata, a statistically significant negative correlation between serum zinc levels and severity of the disease was found (ρ = 0.006). The results indicate that zinc serum assessment is necessary in patients with alopecia areata. Low serum zinc levels were found to correlate with severity of alopecia areata. Given that most severe forms of alopecia areata are frequently most treatment-resistant, additional randomized control trials examining zinc supplementation are necessary to investigate its potential role in the restoration of hair follicles.

Mastocytosis in children: a single-center long-term follow-up study.

BACKGROUND: Mastocytosis is a heterogeneous group of rare disorders characterized by the accumulation of clonal mast cells in organs such as the skin and bone marrow. The diagnosis of cutaneous mastocytosis (CM) is based on clinical findings, positive Darier's sign, and histopathology, if necessary. METHODS: Medical records of 86 children with CM diagnosed during a 35-year long period were reviewed. Most patients (93%) developed CM during the first year of life (median age 3 months). Clinical features at presentation and during the follow-up period were analyzed. Baseline serum tryptase level was measured in 28 patients. RESULTS: A total of 85% of patients had maculopapular cutaneous mastocytosis/urticaria pigmentosa (MPCM/UP), 9% had mastocytoma, and 6% had diffuse cutaneous mastocytosis (DCM). Boy to girl ratio was 1.1:1. Fifty-four of 86 patients (63%) were followed from 2 to 37 years (median 13 years). Complete resolution was registered in 14% of mastocytoma cases, 14% of MCPM/UP, and in 25% of DCM patients. After the age of 18, skin lesion persisted in 14% mastocytoma, 7% MCPM/UP, and 25% children with DCM. Atopic dermatitis was diagnosed in 9.6% of patients with MPCM/UP. Three of 28 patients had elevated serum tryptase. Prognosis in all patients was good, and there were no signs of progression to systemic mastocytosis (SM). CONCLUSION: To the best of our knowledge, our results represent the longest single-center follow-up study of childhood-onset CM. We found no complications of massive mast cell degranulation or progression to SM.

Level and avidity of antineutrophil cytoplasmic antibodies specific to lactoferrin are useful biomarkers in systemic lupus erythematosus.

OBJECTIVES: To evaluate specificity, level, and avidity of antineutrophil cytoplasmic antibodies (ANCA) in systemic lupus erythematosus (SLE). There are no studies of ANCA avidity in SLE. METHODS: Level (ELISA) and avidity (ELISA) of myeloperoxidase (MPO-), proteinase 3 (PR3-), lactoferrin (LF-), cathepsin G, elastase (EL-), and bactericidal/permeability increasing protein (BPI)-ANCA in 142 SLE patients were studied. SLE activity was measured by SLEDAI-2 K. 25/40 ANCA-positive patients were immunoserologically followed (12 ± 2 months). RESULTS: 40/142 (28.2%) SLE patients were ANCA-positive: LF- (21/40), MPO- (19/40), EL- (6/40), PR3- (3/40), and BPI-ANCA (1/40). Only LF-ANCA were associated with renal manifestations (p < 0.05), and positive predictive value for renal involvement in ANCA-positive SLE was 76.2%. LF-ANCA-positive patients had higher SLEDAI-2 K (p < 0.05) and more frequently had anti-dsDNA (p < 0.05), low C3 (p < 0.001), and low C4 (p < 0.05) than LF-ANCA-negative patients. LF-ANCA level was in a positive correlation with SLEDAI-2 K, anti-dsDNA, and anti-C1q (p < 0.01) and in a negative correlation with C3 and C4 (p < 0.05). LF-ANCA avidity was higher than MPO-, EL-, PR3-, and BPI-ANCA avidity (p < 0.01). In LF-ANCA-positive patients, renal manifestations were associated with higher LF-ANCA level (p < 0.01) and avidity (p < 0.05). Based on LF-ANCA level and avidity, the receiver operating characteristic curves for discriminating patients with and without renal involvement had areas under the curves of 0.988 (95% CI: 0.949-1.00) and 0.813 (95% CI: 0.607-1.00), respectively. After the follow-up period, number of LF-ANCA-positive patients decreased (p < 0.01). CONCLUSIONS: In contrast to other ANCAs, only LF-ANCA level correlated with activity and standard serological SLE markers. LF-ANCA level and avidity might be biomarkers of renal involvement in SLE. LF-ANCA are promising serological marker in SLE. Key Points • LF- and MPO-ANCA were most frequently found, while EL-, PR3-, and BPI-ANCA were rarely detected in SLE. • In contrast to other ANCAs, only LF-ANCA were associated with renal involvement, and their level correlated with the activity and standard serological markers of SLE. • LF-ANCA avidity was higher than other ANCAs' avidity; LF-ANCA level and avidity might be useful biomarkers of renal manifestations in SLE. • Detection of ANCA specificity, level, and avidity may help in the diagnosis of particular clinical SLE phenotypes.

Annular lichenoid dermatitis of youth-Recurrent case of rare skin disease treated with cyclosporine.

Annular lichenoid dermatitis of youth (ALDY), first described in 2003, represents an uncommon entity whose etiopathogenesis is still debated. Futhermore, the optimal treatment for ALDY is yet to be established. We report a 9-year-old girl who presented with annular and oval erythematous lesions mostly on her trunk, with several lesions on the neck, groin, flanks, and upper extremities. The lesions had histological and immunohistochemical features characteristic for ALDY. Treatment with H1-antihistamines, topical corticosteroid, and UVB therapy was unsuccessful, while systemic treatment with cyclosporine induced complete remission.

Combined intravenous pulse and topical corticosteroid therapy for severe alopecia areata in children: Comparison of two regimens.

There is no universally accepted treatment for severe pediatric alopecia areata (AA). This prospective study comprised 73 patients (aged 1-18 years) with severe AA (>30% of scalp surface area): 37 received 1-day intravenous dexamethasone pulses (1-DP) and 36 received 3-day pulses (3-DP), monthly, for 6-12 months. Also, all patients applied topical clobetasol propionate under plastic wrap occlusion. Patients achieving >50% regrowth were considered good responders (GR). All patients reached short term, while 65/73 were available for the long-term follow-up (mean 33.3 ± 15.3 vs. 27.7 ± 14.3 months, 1-DP and 3-DP, respectively). Relapses during therapy were more frequent in 1-DP group. 3-DP patients were more frequently GR in comparison with 1-DP. 3-DP patients with disease duration <6 months had better outcomes. Patients without Hashimoto thyroiditis (HT) had 9.8-fold higher chance of being GR in comparison with HT patients. The best results were achieved in AA plurifocalis (AAP). No patient had severe short-term side-effects. At the long-term follow-up, 67% of 3-DP patients had stable results. Only 14.2% AAP patients experienced relapses. Patients had no long-term side-effects. 3-DP were more efficacious than 1-DP. Short disease duration and no HT were good prognostic factors. 3-DP protocol is well-tolerated, with beneficial effects and long-lasting results in severe pediatric AA.

Penicillin-induced Cutaneous Necrotizing Eosinophilic Vasculitis with Cryofibrinogenemia.

Cutaneous necrotizing eosinophilic vasculitis (CNEV) is a rare type of vasculitis. Eosinophilic vasculitis is a necrotizing vasculitis with eosinophilic vascular infiltration, in which eosinophils mediate vascular damage in the disease process. We present a case of an 18-year-old girl who developed palpable purpura and hemorrhagic bullae over the lower extremities associated with itching, 7 days after the commencement of penicillin therapy. Plasma cryofibrinogen was positive. Histopathology showed an infiltration of eosinophils within and around the vessel walls and a complete absence of nuclear dust and neutrophils. Oral prednisone at 1 mg/kg induced remission in 2 weeks; the prednisone dose was tapered and discontinued after 2.5 months. There was no evidence of recurrence after 37 months of follow-up. Our patient represents a rare case of drug/penicillin-induced CNEV associated with cryofibrinogenemia, without systemic organ involvement.

Pregnancy-Induced Sweet's Syndrome Treated with Infliximab.

OBJECTIVE: To present a case of relapsing and resistant Sweet's syndrome that developed during pregnancy together with an onset of Crohn's disease, showing complete resolution with the use of infliximab. CLINICAL PRESENTATION AND INTERVENTION: A 30-year-old pregnant woman presented with fever, skin lesions, and diarrhea. Skin biopsy confirmed neutrophilic dermatosis and she was diagnosed with Crohn's disease after endoscopy. There was no recurrence of Sweet's syndrome outside of her pregnancy. During a previous pregnancy, while corticosteroids were ineffective, complete regression of skin lesions was achieved using infliximab. CONCLUSION: The "off-label" use of infliximab is beneficial for relapsing and resistant Sweet's syndrome.

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.

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.

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.

Stevens-Johnson syndrome and toxic epidermal necrolysis: a 20-year single-center experience.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening diseases that are most frequently caused by drugs. OBJECTIVES: The purpose of this study was to summarize 20 years of experience with SJS and TEN in the largest dermatology clinic in Serbia. METHODS: The study included 38 patients treated during the period 1993-2012. The patients were classified into three groups according to whether they were diagnosed with SJS, a condition representing an overlap of SJS and TEN (SJS/TEN), or TEN. Patients with TEN were also divided into three groups according to the modality of therapy: supportive therapy (ST) only (n = 3); ST plus systemic corticosteroids (SC) (n = 8); and ST plus SC plus IV immunoglobulins (IVIG) (n = 6). RESULTS: The study population included 13 SJS patients, eight SJS/TEN patients, and 17 TEN patients. The disease had started at a mean ± standard deviation (SD) of 7.1 ± 3.5 days after the commencement of treatment with the offending drug. The disease resulted in three lethal outcomes, all of which occurred in TEN patients. However, the predicted mortality for the whole group was 5.6 in 38 patients, whereas that for the TEN group was 3.97 in 17 patients. The differences between actual and predicted rates of mortality were not significant. Among the three groups of TEN patients, there were no significant differences in the commencement of re-epithelialization or the duration of hospitalization. CONCLUSIONS: In the present study, nonsteroidal anti-inflammatory and anti-infective drugs were the most frequent causative agents (eight patients in each group). In the group of SJS and SJS/TEN patients treated with ST and SC, the mortality rate was 0%. In TEN patients, the mortality rate was 17.6% (three of 17 patients). There were no significant differences in mortality rate among the three TEN treatment groups, but the results may have been biased by the small number of patients.

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 Wegener's 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.

Acrokeratosis paraneoplastica Bazex syndrome associated with esophageal squamocellular carcinoma.

BACKGROUND: Acrokeratosis paraneoplastica Bazex (APB) is a very rare disease in the group of obligate paraneoplastic dermatoses, associated mostly with squamous cell carcinoma of the upper aerodigestive tract and metastatic cervical lymphadenopathy. The disease is characterized by violaceous erythemosquamous changes on the acral regions. This entity was first reported by Bazex in 1965. About 160 cases have been presented so far. CASE REPORT: We presented a patient with a three-month history of violaceous erythema, edema, erosions and scaling on the acral regions, elbows and knees and severe nail dystrophy. When the diagnosis was established, he did not have any symptom of internal malignancy. Esophagogastroscopy revealed ulcerovegetant lesion of the esophagus, while histology showed squamocellular invasive carcinoma. Surgical tumor removal resulted in significant improvement of skin changes in 15 days. Unfortunately, four months later, extensive skin lesions pointed to metastasis of squamous cell carcinoma. CONCLUSION: Skin changes can precede a few years the first manifestations of neoplasia. The course of the disease in our patient proved that APB is a specific marker of underlying malignancy.

Pagetoid reticulosis of Woringer-Kolopp.

Pagetoid reticulosis of Woringer-Kolopp is a rare form of cutaneous T-cell lymphoma that primarily affects middle-aged males. It is characterized by the presence of one or several scaly patches and plaques with an acral distribution. We present a case of a 58-year-old woman, otherwise healthy, with a 5-month history of asymptomatic, hyperkeratotic plaques on the hands and feet. Histological and immunohistochemical analysis confirmed the diagnosis. Nearly complete spontaneous regression was noted 7 months after the initial examination. After 5 years no evidence of the disease remained.