Comparison of Intralesional Sodium Stibogluconate versus Intralesional Meglumine Antimoniate for the Treatment of Leishmania major Cutaneous Leishmaniasis.

Israel is endemic for Old-World cutaneous leishmaniasis. The most common species is Leishmania major. However, the available treatment options are limited. This study's objective was to compare the authors' experience with different antimony intralesional treatments of Leishmania major cutaneous leishmaniasis. A retrospective evaluation was undertaken for cases of Leishmania major cutaneous leishmaniasis treated by pentavalent antimony in a university-affiliated medical centre in Israel. The previous treatment of intralesional sodium stibogluconate (Pentostam®) was compared with the current treatment of meglumine antimoniate (Glucantime®). One hundred cases of cutaneous leishmaniasis were treated during the study period, of whom 33 were treated with intralesional sodium stibogluconate and 67 were treated with intralesional meglumine antimoniate. The patients were 78 males and 22 females, mean age 24 (range 10-67) and there was a total of 354 skin lesions. Within 3 months from treatment, 91% (30/33) of the intralesional sodium stibogluconate group and 88% (59/67) of the intralesional meglumine antimoniate group had complete healing of the cutaneous lesions after an average of 3 treatment cycles (non-statistically significant). In conclusion, the 2 different medications have the same efficacy and safety for treating cutaneous leishmaniasis. Pentavalent antimoniate intralesional infiltration treatment is safe, effective, and well tolerated with minimal side effects for Old-World cutaneous leishmaniasis.

Diagnostic delay, comorbid hidradenitis suppurativa and the prognostic value of bacterial culture in folliculitis decalvans: A cohort study.

BACKGROUND: Folliculitis decalvans (FD) is a type of primary neutrophilic cicatricial alopecia often leading to irreversible hair loss. Data on its epidemiology, clinical features, outcomes, and prognostic factors are limited. OBJECTIVE: To evaluate a cohort of patients with FD and identify characteristics of severe disease and prognostic factors which impede remission. PATIENTS AND METHODS: This retrospective cohort study included 192 patients diagnosed with FD and followed for at least six months at a tertiary center between 2010 and 2020. RESULTS: There was a diagnostic delay averaging 22.2 (± 29.7) months. Comorbid follicular occlusion disorders were common. Bacterial cultures were positive in 45.6% of the cases, with Staphylococcus (S.) aureus being the most common pathogen. Severe disease was associated with comorbid hidradenitis suppurativa and a positive bacterial culture, particularly S. aureus. 50.7% of patients experienced complete remission: 32% within the first six months of treatment and 18.7% later during follow-up. Relapses were frequent. Negative prognostic factors for achieving remission included younger age and a positive bacterial culture. CONCLUSIONS: There is a need for the education of dermatologists to reduce the diagnostic delay. Screening FD patients for comorbid hidradenitis suppurativa and obtaining bacterial cultures is important for treatment planning.

Safety of COVID-19 mRNA vaccination and effects of SARS-CoV-2 infection in children and adults with mast cell disorders.

Mastocytosis is characterized by abnormal clonal mast cell proliferation. Given the paucity of data in patients with mastocytosis, it is crucial to assess the safety of COVID-19 vaccines in this population. We aimed to assess the risk of allergic reactions and the effect of COVID-19 infection among patients with mastocytosis. Participants were recruited from Canada and Israel between December 2021 and May 2022. Consenting participants were administered standardized questionnaires querying whether they were infected with COVID-19, if they received the first and second dose vaccines, and post-vaccination side effects including allergic reactions (urticaria/angioedema, current rash flaring, need for updosing medications, or respiratory symptoms) and common side effects including injection site reaction (ISR) and flu-like symptoms. Forty participants with mastocytosis were administered a standardized questionnaire (median age = 9, 59% male). Amongst all participants, 16 (39%) reported COVID-19 infection and most (75%) reported flu-like symptoms, 3 (19%) were asymptomatic, 1 suffered from shortness of breath/chest pain and 1 from facial flushing. Of the 25 participants who were eligible for vaccination (≥ 5 years old), 80% received a first-dose vaccine and 68% received a second-dose vaccine. Of those who received the first-dose vaccine, most (60%) remained asymptomatic, 20% developed flu-like symptoms, 20% had an ISR, and 1 patient had an allergic reaction (urticaria and swelling). Of those who received the second-dose vaccine, most (53%) were asymptomatic, and 1 had an allergic reaction. No significant difference was found between side effects of both vaccine doses. No reactions fulfilled the criteria for anaphylaxis in either dose. This study reveals that among patients with mastocytosis, COVID-19 vaccine and infection were well-tolerated in the majority of cases.

Pediatric Contact Dermatitis: A 10-Year Multicenter Retrospective Study.

Background: Although allergic contact dermatitis (ACD) is relatively common in the adult and pediatric populations alike, few studies describe the special features of contact sensitization among the Israeli pediatric populations, none of them is multicenter. Our study aims to describe and analyze patch test results and trends in 4 tertiary care centers between 2012 and 2022. Methods: We assessed the results of 357 patch tests performed on children 0-18 years old between 2012 and 2022 in designated clinics in 4 tertiary medical centers. All patients were tested using the European baseline series and additional series as clinically indicated. We assessed the demographic features, atopic features, and influence, as well as the main allergens to cause sensitization and allergic contact dermatitis among the pediatric population. Results: In total 69% of the study population were females, mainly 12-18 years old, 35% of the study population were previously diagnosed with atopic dermatitis, and 57% had an atopic diathesis. Females were more commonly sensitized (P < 0.05). Patients without atopic dermatitis were more commonly diagnosed with ACD and had more reactions on patch test (P < 0.05). The most common allergens to cause ACD are preservatives and metals, as previously described, however, acrylate sensitivity is an emerging group that has not been described among the Israeli pediatric population in previous studies. Fragrance mix 2 and Mroxylon pereirae are relatively rare allergens among the Israeli pediatric population, whereas linalool hyperoxide might be considered an emerging allergen. Methylisothiazolinone causes ACD more frequently among patients without atopic dermatitis (P < 0.05). Conclusions: Among the Israeli pediatric population, ACD is more common in females without atopic dermatitis. Acrylates become a common culprit and should be included in baseline series. Patients with atopic dermatitis are less frequently sensitized by methylisothiazolinone.

Coexistence of malignancies in pemphigus vulgaris.

Pemphigus vulgaris (PV) is a rare autoimmune intraepidermal bullous disease. PV has a major effect on morbidity as well as quality of life. There is sparse literature regarding the association between pemphigus vulgaris (PV) and comorbid malignancies. In this study we aimed to assess the risk of malignancy in a cohort of patients with PV and characterize PV-associated malignancies. Data were collected from two tertiary referral centers between the years 2008 and 2019 and compared with the national cancer registry. Of 164 patients with PV, 19 were diagnosed with malignancy: seven prior to PV diagnosis and 12 after. All cancers, solid and hematological, displayed higher incidences compared to the general population (p <0.001). In conclusion, we demonstrated higher rates of malignancies among patients with PV than in the general population. These observations suggest the need for careful assessment and follow up of patients with PV, given the possibility of associated malignancies.

Biological treatment for bullous pemphigoid.

Background: Bullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease. Topical or systemic corticosteroids are often used as the first-line treatment. However, long-term corticosteroid use may lead to significant side effects. Therefore, various adjuvant immunosuppressant therapies are used as steroid-sparing agents, with accumulating reports of biological treatments for severely recalcitrant BP. Objective: To describe the clinical and immunological features of a series of patients with recalcitrant BP treated with immunobiological therapies. To assess the efficacy and safety of their therapies. Methods: Patients receiving biological treatment for BP from two centers were assessed. Here, we described the clinical, immunopathological, and immunofluorescence findings of adult patients with BP and analyzed the clinical response and adverse events associated with various biological therapies. Results: We identified nine eligible patients treated with rituximab (seven), omalizumab (three), or dupilumab (one). The mean age at diagnosis was 60.4 years, the average BP duration before biologic initiation was 1.9 years, and the average previous treatment failure was 2.11 therapies. The mean follow-up period from the first biological treatment to the last visit was 29.3 months. Satisfactory response, defined as clinical improvement, was achieved in 78% (7) of the patients, and total BP clearance was achieved in 55% (5) of the patients at the last follow-up visit. Additional rituximab courses improved the disease outcomes. No adverse events were reported. Conclusions: Efficient and safe novel therapies can be considered in recalcitrant steroid-dependent BP non-responsive to conventional immunosuppressant therapies.

Bullous pemphigoid and dipeptidyl peptidase-4 inhibitors: evaluation of clinical course and treatment response.

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP4is), drugs used to treat type 2 diabetes mellitus (DM2), show a significant association with bullous pemphigoid (BP) development. OBJECTIVES: To evaluate the clinical course and development of BP among patients with DM2 treated with DPP4is. METHODS: This retrospective cohort study included all the patients with BP and comorbid DM2 who visited Sheba Medical Center during 2015-2020. RESULTS: Among 338 patients with BP, 153 were included in our study. In 92 patients, BP diagnosis was attributed to the use of DPP4is. The patients with DPP4i-associated BP had fewer neurological and cardiovascular comorbidities and higher blistered body surface area (BSA) at first presentation, with noticeable upper and lower limb involvement. These patients were younger and more responsive to treatment, with a greater reduction in their BSA score after 2 months of treatment. CONCLUSIONS: The clinical features of patients with BP treated with DPP4is were initially more severe; however, during follow-up, a marked clinical improvement was noticed, especially among patients who had ceased the drug. Therefore, although withdrawal of the drug may not impose disease remission, it can alleviate the disease course and avert the need for treatment escalation.

Prevalence, Spectrum and Clinical Implications of Malignancies in Patients with Bullous Pemphigoid.

Current research on the malignancy rate and spectrum of malignancies in patients with bullous pemphigoid is contradictory. The aims of this study were to determine the prevalence and spectrum of malignancy in patients with bullous pemphigoid and to compare demographic, clinical, therapeutic and outcome data between bullous pemphigoid patients with and without malignancy. This retrospective cohort study enrolled 335 patients (194 women and 141 men; mean age at diagnosis of bullous pemphigoid 77.5 ± 12 years) followed up at an Israeli tertiary centre between January 2009 and December 2019: 107 (32%) had malignancy and 228 (68%) did not. Malignancy occurred before and after bullous pemphigoid diagnosis in 82 (77%) and 25 (23%) patients, respectively. Bullous pemphigoid patients with cancer were older (p = 0.02) and had a higher mortality rate (p < 0.0001) than those without malignancy. The 2 groups did not differ in terms of sex, comorbidities, or clinical characteristics. Those who developed malignancy before bullous pemphigoid were younger than those who developed malignancy after bullous pemphigoid (mean age 69.3 vs 82.4 years, p < 0.0001). Overall malignancy rates did not differ between patients with bullous pemphigoid and the general population; therefore, comprehensive malignancy workup may be unnecessary. However, patients with bullous pemphigoid had a greater risk of melanoma (10.7% vs 4.3%, p = 0.0005); therefore, routine skin screening may be recommended.

The Role of Histological Examination of Nail Clipping in the Diagnosis of Onychomycosis.

BACKGROUND: Diagnosis of onychomycosis is based on potassium hydroxide (KOH), direct smear, culture, and polymerase chain reaction. Nail clippings are rarely used as a diagnostic tool. OBJECTIVES: To evaluate nail clippings for the diagnosis of onychomycosis and to compare it to KOH smears. METHODS: Nail clipping specimens of 39 patients were collected: 34 with onychomycosis proved by positive culture and 5 from normal nails. The specimens were submitted to histological processing and then stained with periodic acid-Schiff (PAS) and Grocott-Gomori's methenamine silver (GMS) stains. For each nail, KOH smear was also performed. Two pathologists who had no information on the KOH smear and the culture results evaluated the nail clipping histology for the presence of fungal element. Their assessment was compared to the KOH smear and culture results. RESULTS: Of the 34 specimens that had positive culture, 25 were dermatophytes, 5 were molds, and 4 were candida. Clipping specimens were positive in 30 cases (88%): 23/25 dermatophyte, 4/5 molds, and 3/4 candida. Pathologists were able to classify the pathogens into dermatophytes and non-dermatophytes based on the morphology. PAS stain results were the same as GMS in evaluation of the nail specimen. KOH smear was positive in 29 nails (85%): 20/25 dermatophytes, all 5 molds, and 4 candida. In all five nails where the culture was negative, both clipping and KOH smear did not show fungal elements. CONCLUSIONS: Nail clippings can serve as a rapid, inexpensive, and reliable method for evaluation of onychomycosis, comparable to KOH smear, with the advantage of pathogen group identification.

Skin Eosinophil Counts in Bullous Pemphigoid as a Prognostic Factor for Disease Severity and Treatment Response.

Dermal infiltration of eosinophils and eosinophilic spongiosis are prominent features of bullous pemphigoid lesions. Although several observations support the pathogenic role of eosinophils in bullous pemphigoid, few studies have examined the impact of skin eosinophil counts on disease severity and treatment response. This retrospective study assessed the association between eosinophil counts in skin biopsy samples of 137 patients with bullous pemphigoid and their demographic characteristics, comorbidities, disease severity, and treatment response. There was no relationship between eosinophil count and age, sex, or disease severity at disease onset. There was a positive relationship between eosinophil counts and neurological comorbidity and a negative relationship between eosinophil counts and treatment response. At all follow-up points patients with no tissue eosinophils had a better response to treatment than patients with any tissue eosinophil count. In conclusion, skin eosinophil counts in patients with bullous pemphigoid are not correlated with disease severity at onset, but can serve as a negative prognostic marker for treatment response.

New-Onset Guttate Psoriasis: A Long-Term Follow-Up Study.

BACKGROUND: Guttate psoriasis (GP), a distinct variant of psoriasis, is more common in children and adolescents. The long-term course of these patients has sparsely been examined, with few studies reporting the rates of relapse, persistence, and further development of the psoriasis vulgaris phenotype. OBJECTIVES: The objective of this study was to characterize the long-term outcomes of new-onset GP and elucidate the potential factors associated with a persistent disease course. METHODS: This was a retrospective cohort study. Patients diagnosed with new-onset GP between 2009 and 2020 with a follow-up period of at least 1 year, were enrolled. The examinees were evaluated by dermatologists. Detailed data retrieved from the examinees' medical files included demographics, disease characteristics, treatment, and comorbidities. A structured telephone questionnaire was used to determine the current psoriasis status: type, severity, and extent. At the end of follow-up, patients with a persistent disease course, defined as having lesions at least a year after disease onset, were compared with patients in complete remission without further psoriasis symptoms. RESULTS: A total of 120 patients (mean age 28.8 years [±15.2], 58.3% women) with new-onset GP flare were identified. At the end of follow-up period (mean 6.2 years [±3.1]), 49.1% (n = 59) of the patients reported active persistent psoriasis. A switch to the psoriasis vulgaris phenotype occurred in 17.5% (n = 21) of the study cohort. Persistent psoriasis was associated with male sex (OR = 2.1, p < 0.05), multiple disease flares (>3; OR = 9.1, p < 0.001), switch to the vulgaris phenotype (OR = 4.16, p < 0.001), and palmoplantar involvement (OR = 5.2, p < 0.01). CONCLUSION: A persistent disease course is common among patients with new-onset GP, with most retaining their guttate phenotype throughout the disease course. Persistency was associated with male sex, multiple GP flares, switching to the vulgaris phenotype, and palmoplantar involvement.

Changing spectrum of hair and scalp disorders over the last decade in a tertiary medical centre.

BACKGROUND: Hair- and scalp-related disorders (HSRDs) encompass a wide range of conditions that affect people of all ages. OBJECTIVE: To evaluate the workload and trends in HSRDs at an outpatient dermatological clinic in a tertiary medical centre over a 10-year period. METHODS: Medical records for HSRD visits to the outpatient dermatology clinic at the Sheba Medical Center, an Israeli tertiary care center, were reviewed between 1 January, 2010 and 31 December, 2020. RESULTS: There were 10,396 HSRD visits with a new-to-follow-up visit ratio of 1:1.9. The annual number of HSRD visits, as well as their proportion out of all dermatological outpatient visits, have increased from 295 (1.24%) in 2010 to 1726 (9.44%) in 2020. The patients' mean age was 35.3 years (women 39.5 years, men 28.8 years), age range 1-87 years. Over the decade, there was a growing predominance of women with an average female-to-male ratio of 2:1. The winter season accounted for 28.7% of annual visits, followed by the autumn (25.6%), summer (24.3%) and spring (21.4%). The most prevalent HSRDs included androgenetic alopecia (30.6%), alopecia areata (19.3%), telogen effluvium (15.4%), non-scarring folliculitis (15.4%), seborrheic dermatitis (14.9%), lichen planopilaris (7.1%) and folliculitis decalvans (6.6%). Androgenetic alopecia demonstrated the highest increase over the decade examined (from 17% to 32%). CONCLUSION: HSRDs account for a significant percentage of visits at a tertiary dermatology outpatient clinic. The number of HSRD visits has increased annually over the past decade. The recent advancement in diagnosis and treatment may account, at least in part, for the growing burden of HSRDs within dermatological ambulatory care.

Validation of the Urticaria Control Test (UCT) in Children With Chronic Urticaria.

BACKGROUND: Few validated tools exist to evaluate chronic urticaria (CU) control in children. Although the Urticaria Control Test (UCT) exhibits favorable clinometric properties in adult CU, it is not yet validated in children. OBJECTIVE: To evaluate the validity of the UCT for the assessment of pediatric CU. METHODS: Children presenting with CU were consecutively recruited and completed both the UCT and the Children's Dermatology Life Quality Index (CDLQI) at study entry. Using the CDLQI as an anchor, we assessed the internal consistency, convergent and known-groups validity, and screening accuracy of the UCT at study entry and at follow-up. RESULTS: A total of 52 children with CU were recruited. The UCT exhibited respectable internal consistency in the evaluation of CU (Cronbach's α, 0.73; 95% CI, 0.62-0.85). UCT and CDLQI scores strongly correlated (r = -0.74; P < .01). The UCT distinguished between different strata of disease severities established by the CDLQI (P < .01). Screening accuracy of the UCT was excellent in the discrimination of poorly controlled CU (area under the curve, 0.82). An optimal cutoff of less than or equal to 10 was determined for defining poorly controlled CU (sensitivity, 95.5%; specificity, 63.3%). Data at follow-up were consistent with data at study entry. Subgroup analyses of patients with chronic spontaneous urticaria were consistent with overall estimates of validity. CONCLUSIONS: The UCT is a valid tool for the assessment of pediatric CU and chronic spontaneous urticaria, as evidenced by the acceptable internal consistency, convergent and known-groups validity, and screening accuracy at multiple time points.

Illness Perception Regarding Early-stage Mycosis Fungoides among Dermatologists: A Multi-centre Cross-sectional Study.

Early-stage mycosis fungoides is a rare cutaneous T-cell lymphoma with a good prognosis. Data regarding patients' illness perception of mycosis fungoides are accumulating. However, investigating the dermatologists' viewpoint is also essential, as it shapes the therapeutic relationship and doctor-patient communication. The aim of this study was to investigate the aspects of dermatologists' illness perception towards early-stage mycosis fungoides and the way they present it to patients. Twenty-five dermatology residents and 55 attending physicians from all Israeli dermatology departments and the community completed the study questionnaires online. Dermatologists viewed mycosis fungoides as a chronic disease, causing a moderate emotional burden. In contrast to previously published data regarding patients' illness perception, dermatologists demonstrated dominancy in the notion that patients were able to control their disease. Most dermatologists thought that patients perceived mycosis fungoides as an indolent lymphoma that causes anxiety. Dermatologists used a high diversity of themes when presenting mycosis fungoides to patients. The differences between the residents' and attending physicians' perceptions were minimal. Dermatologists have a kaleidoscope of views regarding the way they perceive mycosis fungoides, the way they think patients perceive it, and the way they communicate with patients. Maintaining patient-centred communication enables dermatologists to identify these gaps and view mycosis fungoides from their patients' perspective.

Evaluating differential expression of fibrosis-related genes and their correlation with blood vessel density in chronic cutaneous graft-versus-host disease.

BACKGROUND: Sclerodermoid graft-versus-host disease (GVHD) is the most severe form of chronic GVHD (cGVHD) and represents a considerable therapeutic challenge. Due to the scarcity of human studies on sclerodermoid cGVHD, the pathogenesis of this entity is not fully understood. OBJECTIVE: To identify the differential expression of fibrosis-related genes in skin lesions of human lichenoid and sclerodermoid cGVHD and to assess the expression of their corresponding proteins. METHODS: PCR array analysis was performed on RNA extracted from three skin biopsies of sclerodermoid cGVHD patients and three normal skin samples, for fibrosis-related gene expression profiles followed by evaluation of their corresponding protein expressions. The expressions of Tissue inhibitor of metalloproteinase 3 (TIMP3), matrix metalloproteinase 1 (MMP1), TIMP1, and TIMP2 were further studied by immunohistochemistry. Demographic, clinical and immunohistochemical parameters of the two cGVHD groups and the control group were compared. The Pearson correlation coefficient was used to assess the correlation between data among the study groups. RESULTS: We identified 44 upregulated and 14 downregulated genes in the skin samples of sclerodermoid cGVHD compared to the control group. TIMP3 was positive in 13/21 biopsies of cGVHD and in one biopsy of the control group. The average staining intensity was significantly higher in the cGVHD group compared to the control group. TIMP3 was expressed mainly in dermal blood vessels. cGVHD specimens with positive TIMP3 staining had a statistically significantly higher total microvascular area than the negative specimens. CONCLUSION: TIMP3 levels are increased in both subtypes of cGVHD and are associated with increased dermal vascularity.

Relationship Between Pemphigus Vulgaris Severity and PCR-positive Herpes Simplex Virus.

Pemphigus vulgaris is a rare autoimmune skin disease. Although herpes simplex virus has been associated with autoimmune diseases, evidence regarding its association with pemphigus vulgaris exacerbations is scarce. This retrospective cohort study aimed to characterize the epidemiological and clinical features of patients with pemphigus vulgaris who were herpes simplex-positive, compared with those who were herpes simplex-negative, during disease onset. Of 62 patients with pemphigus vulgaris who underwent PCR testing for herpes simplex virus, 25 (40.3%) were positive, with a mean age of 56.1 ± 15.5 years; 35.5% were male. The herpes-positive group had significantly elevated levels of C-reactive protein, Pemphigus Disease Activity Index score, and shorter time to relapse. The time to remission, number of exacerbations per year, and remission status were non-significantly elevated in the herpes-positive group. Thus, routine testing lesions from patients with pemphigus for herpes simplex virus should be performed. If positive, antiviral treatment should be initiated; and preventive antiviral treatment should be considered in severe cases.