Exploring Remission Dynamics and Prognostic Factors in Lichen Planopilaris: a Retrospective Cohort Study.

INTRODUCTION: Lichen planopilaris (LPP) is a common type of primary cicatricial alopecia. Previous studies focused on the epidemiology, clinical characteristics, and treatment of LPP. A lack of knowledge regarding LPP outcomes and prognostic factors remained. METHODS: To delineate the rate and timing of remission in LPP, as well as the prognostic factors for achieving remission, a retrospective cohort study was conducted. The study included 126 patients, from a single tertiary center, diagnosed with LPP between January 2010 and December 2022, who were followed up for a minimum of 6 months. RESULTS: There were 89 (70.6%) women and 37 (29.4 %) men included in this study. The mean age of the patients was 47.92±14.2 years. The mean time from disease onset to diagnosis was 33.85 (±30) months, indicating significant diagnostic delays. The mean duration of follow-up was 34.13±22.7 months. Among the cohort, 43 patients achieved complete remission (CR) during the follow-up period, whereas 83 patients did not. Of the 83 patients who did not achieve CR, 35 partially improved and 48 did not improve or worsened. The median time for achieving CR was 46±18.8 months. Milder disease at presentation and comorbid lichen planus were associated with higher CR rates. CONCLUSION: This study demonstrates significant diagnostic delays that should be addressed as LPP causes irreversible alopecia, suggests disease severity and comorbid lichen planus as potential prognostic factors. Further, it emphasizes the limited efficacy of current treatments and the need for prolonged treatment in patients with LPP to achieve remission.

Improved effectiveness of an increased dose of griseofulvin for treating Tinea capitis among refugee children in Israel: A retrospective cohort study.

BACKGROUND: Tinea capitis (TC), a fungal infection that occurs in children, is primarily caused by dermatophytes such as Trichophyton and Microsporum species. For Trichophyton species, treatment with terbinafine is considered more effective than griseofulvin treatment. Specific populations, such as refugee children, are more susceptible to TC. OBJECTIVE: This study aimed to describe and compare the response to treatment among Israeli and refugee children with TC. PATIENTS/METHODS: We retrospectively reviewed data collected on refugee and Israeli children with TC between January 2004 and January 2020. RESULTS: Overall, 3358 children with TC (refugees: 1497; Israelis: 1861) were identified. Among these, 86% of the refugee children had TC caused by Trichophyton violaceum, 65% of the Israeli children had TC caused by Microsporum canis and 83% of all children were treated with griseofulvin. Overall, 14% of the refugees showed a partial response to a griseofulvin dose of ≤25 mg/kg/day; however, they showed a complete response upon increasing the dose to ≥30 mg/kg/day. No significant adverse effects were observed. CONCLUSION: The over-crowded day care centres and dense living make refugee children more susceptible to TC than the general population, and griseofulvin dosage adjustment is necessary. TC, due to Trichophyton species, could benefit from receiving an increased dose of griseofulvin in a suspension form, which is cheaper than terbinafine.

Percutaneous ethanol sclerotherapy is a promising treatment for recalcitrant angiolymphoid hyperplasia with eosinophilia.

Angiolymphoid hyperplasia with eosinophilia (ALHE) is a rare benign vascular proliferation, which manifests as characteristic red nodules and papules, mostly located on the scalp and periauricular regions. Patients seek treatment for both aesthetic and functional reasons, as lesions may ulcerate, bleed and itch. Many therapeutic approaches have been reported, with variable success, and relapse remains a troublesome issue. The aim of this study was to report our experience treating ALHE using percutaneous ethanol sclerotherapy (PES). We present a retrospective case series of three patients treated with PES (1-2 treatment sessions each). All patients had tried and failed other treatments prior to this intervention, but following PES treatment, all patients demonstrated significant improvement, which was sustained at follow-up (range 8-17 months after first treatment). Adverse effects were tolerable and transient. This case series demonstrates PES as a promising treatment for recalcitrant ALHE.

Interleukin-17 is a potential player and treatment target in severe chronic spontaneous urticaria.

BACKGROUND: Chronic spontaneous urticaria (CSU) is considered an autoimmune disorder in 50% of cases at least, in which T- and mast cell mediators are considered to be the primary cause of symptoms. However, H1 -antihistamines, cyclosporine A, and omalizumab fail to achieve complete symptom amelioration in up to 70% of patients. This suggests that other inflammatory pathways are involved and that additional and more effective treatments need to be developed. OBJECTIVE: This preliminary report examines the possibility that interleukin-17 (IL-17), a cytokine involved in the pathogenesis of many autoimmune diseases, may contribute to CSU and its inhibition may offer a relevant therapeutic target. METHODS: The expression of IL-17A in skin biopsies of 20 CSU patients and 10 healthy controls was determined by quantitative histomorphometry. We also assessed the response to secukinumab (anti-IL-17A) treatment patients of eight severe CSU (7-day urticaria activity score UAS7 32-40) who were H1 -antihistamine and omalizumab-resistant. RESULTS: Increased numbers of CD4+ T cells and mast cells were present in both lesional and non-lesional skin of CSU patients compared with healthy controls. Both types of cells were strongly positive for IL-17A and found to be in close proximity to each other. All eight patients treated with the anti-IL-17A antibody, secukinumab, showed significant improvement in CSU disease activity. The action of secukinumab was shown to be relatively slow in onset. The significant reduction in disease activity from baseline UAS7 was demonstrated to be 55% and 82% at 30 and 90 days, respectively. CONCLUSIONS: These findings suggest that IL-17 is involved in the pathogenesis of CSU and that IL-17 should be investigated as a therapeutic target in future studies with larger numbers of patients.

Characteristics of patients with bullous pemphigoid: comparison of classic bullous pemphigoid to non-bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal autoimmune blistering disease. Patients occasionally present with a clinical picture of pruritus/urticaria alone for months and do not even develop blisters over time. Only few studies have investigated this subgroup of non-bullous pemphigoid (NBP). OBJECTIVE: To evaluate the demographic and clinical characteristics of BP patients with or without blisters at the time of diagnosis. METHODS: A retrospective study based on the medical records of 115 BP patients. Collected data included demographic characteristics, clinical presentation, treatment and response to treatment. RESULTS: Thirty-six patients presented with pruritus/urticaria (31.3%), and 79 presented with blisters (68.7%), with mean ages of 77.5 and 76.0, respectively, at diagnosis and an equal female:male ratio. The level of immunoglobulin E (IgE) was 4.1 times higher, and the mean blood eosinophil count was significantly increased in the pruritus/urticaria group. Remission rate at 3 months and relapse rate were similar between the groups. Median follow-up period was 9 months (range 3-18). Only 23% of the patients with pruritus/urticaria developed blisters. CONCLUSIONS: A significant number of BP patients present without blisters. We found no significant epidemiological or clinical differences from the classic BP patients aside from significantly elevated IgE and blood eosinophil levels. Similar results in larger cohort studies might be the foundation for a change in clinical protocols regarding the diagnosis and recommended treatment for the elderly presenting with pruritus/urticaria only.

Unilesional mycosis fungoides is associated with increased expression of microRNA-17~92 and T helper 1 skewing.

BACKGROUND: The molecular basis of unilesional mycosis fungoides (MF), characterized by a solitary lesion that is clinicopathologically indistinguishable from multifocal patch or plaque MF (early MF), is unknown. OBJECTIVES: To investigate the microRNA profile in unilesional MF distinguishing it from early MF. METHODS: Biopsy samples of unilesional MF and early MF were evaluated with the Affymetrix microRNA array, with further comparison with inflammatory dermatosis, using quantitative polymerase chain reaction. NanoString technology was applied to analyse the gene expression of T helper (Th)1 immune markers, and immunohistochemistry was used to evaluate CXCR3 and GATA-binding protein 3 (GATA3) markers for Th1 and Th2 cells, respectively. RESULTS: Unilesional MF had a significantly higher level of expression of all members of the microRNA miR-17~92 cluster than early MF. Specifically, unilesional MF had a higher miR-17 level than early MF and inflammatory dermatoses. There was downregulation of the expression of phosphatase and tensin homolog (PTEN) and CREB1, known targets of miR-17~92 members; higher gene expression of interleukin-2 and interferon-γ; and a statistically lower average percentage of GATA3+ dermal cells (6·7% vs. 42·3%), were detected in unilesional MF compared with early MF. High immunoreactivity of CXCR3 was noted in both unilesional and early MF. CONCLUSIONS: Unilesional MF exhibits a microRNA profile distinct from that of conventional early MF, with a higher level of miR-17~92 members along with Th1 skewing. These findings suggest a robust reactive T-cell immune response in unilesional MF and might account for the localized nature of this disease.

Alopecia areata: a long-term follow-up study of 104 patients.

BACKGROUND: Alopecia areata (AA) is a common autoimmune disease that considerably affects the quality of life. Although several studies have investigated the epidemiology, clinical characteristics and treatment of AA, limited recent data are available regarding its long-term course. OBJECTIVES: To evaluate the long-term course of AA in different age groups. METHODS: A retrospective evaluation of patients who were newly diagnosed with AA from 2008 to 2011 and had at least 7 years of follow-up. Data regarding the initial episode, treatment given, disease-free interval and relapses were analysed. RESULTS: A total of 104 cases were analysed: 31 childhood-onset, 63 adult-onset and 10 late-onset. At first episode, 88.5% of patients had mild, 3.8% moderate and 7.7% severe AA. Full or significant re-growth was observed in 74%, 94% and 100% of childhood-onset, adult-onset and late-onset AA patients, respectively. There was no re-growth in 13%, 3% and 0% of childhood-onset, adult-onset and late-onset patients, respectively. The duration of the initial episode and the disease-free interval negatively correlated with age. Systemic steroids were the most effective treatment for the primary episode. The frequency of relapses was high overall (52%, 44% and 30% in childhood-onset, adult-onset and late-onset, respectively), but significantly declined over time with a majority (79%) occurring within the first 4 years. The disease-free interval and relapse rate were not correlated with gender, disease severity at onset or treatment given. CONCLUSIONS: The prevalence of severe disease, duration of an initial episode and the rate of relapses decreased with an older age at onset. In addition, the outcome and the disease-free interval improved with age at onset. The frequency of relapses declined over time and most appear early on. The current treatment modalities do not seem to influence the long-term outcome.

Neuropsychiatric comorbidity among adolescents with psoriasis.

BACKGROUND: Psoriasis is a known risk factor for neuropsychiatric diseases among adults. Less is known about the impact on adolescents. OBJECTIVES: To investigate the association between psoriasis and neuropsychiatric comorbidity and social skills among adolescents. METHODS: A population-based cross-sectional study between 1 January 1999 and 1 January 2014 was conducted. The study included 1746 and 1366 adolescents (aged 16 to 18) with mild and moderate-to-severe psoriasis, respectively. The psoriasis patients were diagnosed by a dermatologist. Neuropsychiatric diseases were diagnosed by a neurologist and a psychiatrist, as appropriate. Social skills were evaluated using psychosocial assessment. Patients with psoriasis were compared with 884 653 healthy controls by a multivariate analysis adjusted for age, sex, country of origin, socioeconomic status, cognitive skills and body mass index. A subgroup evaluation was done for comorbidity that could only be evaluated for part of the recruitment years, using a univariate analysis. RESULTS: Overall chronic headaches (8·1% vs. 3·4%), intermediate frequency migraine (4·8% vs. 1·6%), low-frequency migraine and nonmigraine headaches (3·4% vs. 1·8%) were associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted odds ratios (OR) 1·9, 95% confidence interval (CI) 1·6-2·4; 2·3, 95% CI 1·8-3·0 and 1·5, 95% CI 1·1-2·1, respectively]. Anxiety disorders (2·1% vs. 0·8%) and impaired social adjustment skills (7·5% vs. 4·2%) were also associated with moderate-to-severe psoriasis only compared with healthy controls [adjusted ORs 2·9, 95% CI 1·6-5·5 and 1·9, 95% CI 1·3-2·6 (of 466 vs. 265 023), respectively]. CONCLUSIONS: Psoriasis among adolescents is associated with neuropsychiatric comorbidity and impaired adjustment skills, depending on disease severity.

Psoriasis comorbidity affects multiple sclerosis neurological progression: a retrospective case - control analysis.

BACKGROUND: Multiple sclerosis (MS) and psoriasis are inflammatory disorders, with epidemiological and biological associations. The impact of one disease on the course of the other has not been studied. OBJECTIVE: To characterize patients with psoriasis and MS, and to assess whether psoriasis comorbidity affected the progression of MS. METHODS: A retrospective case-control study. Patients with psoriasis comorbidity were identified from 3456 patients included in the Sheba Hospital Multiple Sclerosis Center database. Clinical and demographical characteristics and MS progression-related outcomes in patients whose follow-up exceeded 5 years were analysed and compared to those of a matched control cohort of MS-only (MSO) patients. RESULTS: Forty-five (1.3%) MS patients had psoriasis comorbidity. Psoriasis preceded MS in 35 (78%) cases. The psoriasis was defined as mild, moderate and severe in 24 (53%), twelve (27%) and nine (20%) cases respectively. MS progression-related outcomes were evaluated in 35 patients that had follow-up over 5 years. Patients with psoriasis onset preceding relapsing-remitting MS (RRMS) had slower progression of disease compared to MSO patients, as manifested by a longer time to second relapse (P < 0.01) and a longer time to significant neurological disability scores (P < 0.03). CONCLUSION: Psoriasis comorbidity preceding the onset of MS is associated with slower progression of disability.

Unusual forms of cutaneous leishmaniasis due to Leishmania major.

BACKGROUND: Cutaneous leishmaniasis (CL) due to Leishmania major (L. major) is common in the Middle East; however, this skin infection may be under-diagnosed when it presents atypically. OBJECTIVE: To highlight the occurrence of uncommon presentations of CL that may elude diagnosis. MATERIALS AND METHODS: A retrospective study was performed among patients who presented at The Sheba Medical Center between 2005 and 2014 with atypical clinical presentations of CL due to L. major. RESULTS: Twelve patients with unusual clinical presentations of L. major CL were identified. All infections were acquired in L. major - endemic areas of Israel. The average age was 37 years. The average number of lesions was 2. Nine patients presented with a form that mimicked other forms of CL, such as lupoid, giant ulcer, sporotrichoid and recidivans, and three had a variant resembling other infectious skin diseases, such as erysipeloid and verruciform. All patients required systemic therapy. CONCLUSION: Cutaneous leishmaniasis due to L. major can masquerade as many other infectious and inflammatory diseases. In addition, it can mimic clinical forms of New World CL. We suggest that in endemic countries or in travellers returning from countries where L. major is endemic, polymerase chain reaction (PCR) for Leishmania-specific DNA should be performed routinely in cases of unusual presentations of dermatitis with a single or a few lesions, even if a diagnosis of CL was not considered by the referring clinician.

Late-onset onchocercal skin disease among Ethiopian immigrants.

BACKGROUND: Onchocerciasis is an infectious disease caused by the filaria Onchocerca volvulus. Very little is known regarding onchocerciasis imported from endemic to nonendemic areas. OBJECTIVES: To evaluate pruritic dermatitis simulating atopic dermatitis in Ethiopian immigrants in Israel. PATIENTS AND METHODS: A retrospective study of 27 Ethiopian immigrants to Israel was conducted. Demographics and clinical and laboratory data were collected. RESULTS: Of the group of 27 patients, 10 (37%) were men and 17 (63%) were women. The average age at referral was 29 years. All of the patients emigrated from Kuwara, Ethiopia. Diagnosis was done by either positive skin snip test or immunoglobulin (Ig) G4 serology of onchocerciasis in 14 patients. The most common presentation was a combination of lichenified onchodermatitis with atrophy and depigmentation (36%). Eosinophilia and elevated IgE levels were common. Seventeen patients were treated with a single administration of oral ivermectin 200 µg mg(-1). Thirteen patients responded to the treatment. CONCLUSIONS: Immigrants from endemic regions to developed countries presenting with pruritic diseases, especially those with a clinical picture suggestive of atopic dermatitis, should be evaluated for possible onchocerciasis infection. Ivermectin, a relatively safe and low-cost treatment, should be considered even in the absence of a proven disease. Physicians should have a high index of suspicion in patients with the corresponding residential history.

Erysipelas-like erythema as the presenting feature of familial Mediterranean fever.

BACKGROUND: 'Erysipelas-like' erythema (ELE) is a well recognized, although uncommon, manifestation of familial Mediterranean fever (FMF), which is frequently mistaken for infectious erysipelas, especially when forming the initial disease presentation. AIM: To clinically and genetically characterize ELE as the first manifestation of FMF. METHODS: FMF patients with ELE as the first disease presentation (study group), were compared with FMF patients with ELE, appearing during the disease course (control group I), and to those FMF patients who never had ELE (control group II). RESULTS: Patients of the study group were comparable to patients without ELE with respect to all demographic, clinical and genetic features studied, and yet differed from patients with ELE appearing later in the disease course in disease severity score (1.7 ± 0.4 vs. 2.4 ± 0.6, P = 0.01), length of diagnosis delay (7.2 ± 6.4 vs. 2.3 ± 3.3 years, P=0.037), age of FMF onset (24.8 ± 19.9 vs. 5.6 ± 5.7 years of age, P=0.014) and rate of homozygosity to the M694V mutation (14.3% vs. 68.7% respectively). ELE traits in the study and control groups were alike. CONCLUSIONS: FMF with ELE as the first disease manifestation form an uncommon subgroup, clinically and genetically diverging from the rest of the FMF-ELE patients.

Autoimmune syndrome induced by adjuvants (ASIA) in the Middle East: morphea following silicone implantation.

Morphea and other scleroderma-like skin conditions are occasionally linked with exposure to chemical compounds such as silicone. We treated a 56-year-old woman with generalized severe skin induration accompanied with systemic symptoms and peripheral eosinophilia, which appeared 2.5 years after breast silicone implantation and abdominal liposuction. Blood test results and histopathological examination of her skin suggested the diagnosis of morphea overlapping with eosinophilic fasciitis. Her skin disease was presumed to be an autoimmune reaction to silicone implantation. While the removal of the implants did not improve her illness, treatment with 1 mg/kg prednisone and PUVA bath was initiated, with some improvement. This patient illustrates an example of ASIA (Autoimmune Syndrome Induced by Adjuvants), as her disease appeared following exposure to an adjuvant stimulus, with 'typical', although not well-defined, autoimmune manifestations.

NB-UVB (311-312 nm)-induced lentigines in patients with mycosis fungoides: a new adverse effect of phototherapy.

BACKGROUND: Lentigines are a common pigmentary disorder in adults and in patients treated by psoralen and ultraviolet A (PUVA) radiation. Their appearance following treatment with narrow-band ultraviolet B (NB-UVB) radiation has been reported in only two patients. OBJECTIVE: To describe the clinical and histological features of NB-UVB-induced lentigines their relation to dosimetry and the course of the eruption in patients with mycosis fungoides (MF). METHODS: The files of all patients with MF treated in our department in 2003-2010 were searched to identify those in whom lentigines appeared following monotherapy with NB-UVB radiation. RESULTS: Of the 73 patients with early stage MF identified, 10 met the study criteria. Lentigines were detected in skin previously involved by MF in seven patients, and in both involved and uninvolved skin in three patients. They appeared during therapy in three patients, after a mean of 56 exposures (range 50-61), and several months (mean 7.8) following completion of treatment in seven patients, after a mean of 69 exposures (range 32-157). Histopathological study of lesions from five patients revealed basal hyperpigmentation relative to adjacent normal-looking skin. Two lesions had a slight increased number of normal-looking melanocytes on immunohistochemical staining with melanoma cocktail. One lesion had elongated rete ridges. The lesions persisted throughout follow-up (mean 26.7 months) in 8 patients. CONCLUSIONS: Patients with MF treated with NB-UVB may acquire lentigines. As opposed to PUVA-induced lentigines which are a known common side-effect of long-term treatment, NB-UVB-induced lentigines are uncommon but appear earlier, even after a few months of treatment.

The role of therapeutic plasma exchange in pemphigus vulgaris.

BACKGROUND: The treatment of pemphigus, an autoimmune bullous disease, is based on the combination of corticosteroids and adjuvant therapies, such as immunosuppressive drugs, anti-inflammatory drugs and immunomodulatory procedures, such as intravenous immunoglobulin and therapeutic plasma exchange (TPE). OBJECTIVE: This study aims to assess our experience with TPE as a steroid-sparing modality in moderate and severe intractable pemphigus patients. METHODS: A retrospective evaluation for all intractable pemphigus patients treated by TPE in a university-affiliated tertiary referral medical centre between the years 1998 and 2008. Treatment protocol included three TPE treatments weekly for 1-3 months, combined with monthly pulse therapy of dexamethasone and/or cyclophosphamide. Maintenance therapy was based on once/bi weekly TPE treatments or monthly intravenous immunoglobulin. RESULTS: Seven patients were included in the study, four with severe pemphigus vulgaris and three with moderate disease. Six of the seven patients responded to TPE: Four patients (57%) achieved complete remission and two patients (28%) achieved partial remission on minimal therapy. Mild adverse effects related to TPE were observed in two patients and included dizziness and mild headache. CONCLUSION: TPE is a well-tolerated effective steroid-sparing agent in recalcitrant pemphigus patients.

An outbreak of Burkholderia cenocepacia bacteremia in immunocompromised oncology patients.

BACKGROUND: Burkholderia cepacia is a common environmental bacterium that is resistant to disinfectants, and therefore is often encountered as a hospital-acquired pathogen. We describe an outbreak of B. cenocepacia bacteremia among hospitalized oncology patients. METHODS: A matched case-control study and an extensive environmental investigation were conducted. Species were identified by RFLP of the amplified recA gene. DNA was fingerprinted by pulsed-field gel electrophoresis (PFGE). RESULTS: Between November 2005 and September 2006, B. cenocepacia bacteremia developed in 17 patients with underlying malignancy of whom 14 had tunneled central venous catheters. All patients had fever and chills which subsided following removal of the central catheter and administration of ceftazidime. Extensive epidemiological investigation could not find a common source for the outbreak. Patients were hospitalized in three different buildings with different health care personnel. Medications were prepared in different sites by different personnel. A multivariate analysis demonstrated that the independent risk factors for developing nosocomial B. cenocepacia bacteremia were hospitalization at the center for long-term support (OR 28.8; 95% CI 1.83-453.4) and reduced use of antibiotics during the last month (OR 0.07; 95% CI 0.01-0.40). All isolates had identical antimicrobial susceptibility; PFGE indicated that a complex of closely related strains was involved in the outbreak. All isolates were identified as B. cenocepacia, known to infect cystic fibrosis patients. Strict infection control measures terminated the outbreak. CONCLUSIONS: B. cenocepacia is an emerging nosocomial pathogen among oncology patients.

Low-dose methotrexate treatment for moderate-to-severe atopic dermatitis in adults.

BACKGROUND: Atopic dermatitis (AD) is a common inflammatory skin disease. Methotrexate (MTX) was suggested as an effective treatment option in cases of moderate-to-severe atopic dermatitis. This study assessed the efficacy and safety of treatment with low weekly doses of methotrexate for moderate-to-severe AD in adults. METHODS: Twenty adult patients with moderate-to-severe AD were included in this retrospective study. Those patients were unresponsive to topical treatments, antihistamines and at least one of the second-line treatments. MTX in low weekly doses of 10-25 mg was administered orally or intramuscularly with folic acid supplementation 5 mg per week for at least 8-12 weeks. The response to treatment was evaluated by change in SCORAD (SCORing Atopic Dermatitis), DLQI (Dermatology Quality of Life Index) and the global assessment of the clinical response score. RESULTS: After 8-12 weeks of treatment, we observed an objective response in most patients. There were 16 responders and 4 non-responders. The mean SCORAD and DLQI decreased by 28.65 units (44.3%) and 10.15 units (43.5%), respectively. The first improvement was observed after a period ranging from 2 weeks to 3 months (mean 9.95 w +/- 3.17). Treatment was more effective in adult onset AD than in childhood onset. Tolerance of treatment was good. However, nausea and an increase of liver enzymes were observed in 5 patients and 3 of them required a transient discontinuation of MTX. One patient developed peripheral neuropathy, which was resolved several weeks after the discontinuation of MTX. CONCLUSION: MTX seems to be an effective and safe second-line treatment for patients with moderate-to-severe atopic dermatitis. A randomized, controlled study is warranted.