Dermatological changes in a prospective cohort of acutely ill, hospitalised Malawian children, stratified according to nutritional status.

RATIONALE: Since the first documentation of skin changes in malnutrition in the early 18th century, various hair and skin changes have been reported in severely malnourished children globally. We aimed to describe the frequency and types of skin conditions in children admitted with acute illness to Queen Elizabeth Central Hospital, Blantyre, Malawi across a spectrum of nutritional status and validate an existing skin assessment tool. METHODS: Children between 1 week and 23 months of age with acute illness were enrolled and stratified by anthropometry. Standardised photographs were taken, and three dermatologists assessed skin changes and scored each child according to the SCORDoK tool. RESULTS: Among 103 children, median age of 12 months, 31 (30%) had severe wasting, 11 (11%) kwashiorkor (nutritional oedema), 20 (19%) had moderate wasting, 41 (40%) had no nutritional wasting and 18 (17%) a positive HIV antibody test. Six (5.8%) of the included patients died. 51 (50%) of children presented with at least one skin change. Pigmentary changes were the most common, observed in 35 (34%), with hair loss and bullae, erosions and desquamation the second most prevalent skin condition. Common diagnoses were congenital dermal melanocytosis, diaper dermatitis, eczema and postinflammatory hyperpigmentation. Severe skin changes like flaky paint dermatosis were rarely identified. Inter-rater variability calculations showed only fair agreement (overall Fleiss' kappa 0.25) while intrarater variability had a fair-moderate agreement (Cohen's kappa score of 0.47-0.58). DISCUSSION: Skin changes in hospitalised children with an acute illness and stratified according to nutritional status were not as prevalent as historically reported. Dermatological assessment by means of the SKORDoK tool using photographs is less reliable than expected.

Outcome Measures in Adult Vulvar Lichen Sclerosus: A Case Series of Women Diagnosed as Juveniles.

OBJECTIVES: Studies on the consequences of juvenile vulvar lichen sclerosus (JVLS) in adulthood are limited. A number of measuring tools are available for analyzing adult vulvar lichen sclerosus (VLS), but these have not been applied in studies on JVLS. The aim is to study physical findings, quality of life, sexual well-being, and self-image in adult women with a history of juvenile VLS. MATERIALS AND METHODS: Adult women with a biopsy proven history of JVLS were recruited to be examined and surveyed using available standardized measurement tools. This took place in an outpatient setting by physicians who were not involved in the treatment of participants. RESULTS: Twenty-seven women (median age 29 years) with a history of JVLS and median time since biopsy of 19.5 years were recruited. Of these women, 59% currently had symptoms, 63% had signs of active disease, and 85% had moderate to severe architectural changes. Despite these residual signs, vulvar specific-quality of life and vulvar self-image scored favorably while generic health-related quality of life was somewhat effected. CONCLUSIONS: JVLS has consequences in adulthood involving physical findings and vulvar quality of life. The use of standardized outcome measures for clinical practice and research purposes facilitates a better understanding of the sequelae to JVLS.

Growing up with juvenile vulvar lichen sclerosus, the experiences and care needs of adult women with lichen sclerosus since childhood: a qualitative exploration.

BACKGROUND: Vulvar Lichen Sclerosus (VLS) is a chronic remitting condition affecting the genital skin of females of all ages. Although qualitative studies have been conducted focusing on women with VLS in mid-life or older, less is known about the experiences of individuals with VLS from childhood or adolescence onward. OBJECTIVE: To gain understanding of the experiences of women with a history of juvenile VLS (JVLS) regarding the impact of the disease on their personal lives, and their experiences and needs regarding care and guidance. METHODS: A qualitative study was conducted consisting of 27 in-depth face-to-face interviews with adult women with a histologically confirmed history of JVLS, striving for maximum variation and saturation. Interviews were audio-taped and transcribed verbatim. A thorough thematic content analysis was performed. RESULTS: Three main themes were identified. I. Varying impact of living with JVLS: Women experienced diverse emotional and physical impact, from shame and denial to complete acceptance, from restrictions in daily functioning to no limitations. They felt hindered by their own lack of knowledge about JVLS, and generally expressed a positive influence of sharing their experiences with people close to them. II. Finding one's way in care and guidance: While navigating care and guidance, women often felt hindered by knowledge gaps among health care professionals (HCPs), lack of continuity in care and guidance, lack of life-stage adjusted and future-oriented information provision, inadequate guidance around life events, and insufficient monitoring of determinants of therapy adherence. III. Need for patient-tailored care: Patients stressed the need for age-appropriate and life-phase adjusted information, guidance around life-events and compassionate contact with knowledgeable HCPs, aware of the determinants of therapy adherence and influencing factors. CONCLUSIONS: Age-appropriate life-phase adjusted individually tailored care for women diagnosed with VLS in childhood or adolescence is needed. Care and guidance from childhood onward should encompass a standard of care adapted to the individual as needs change over time. This involves taking interpersonal differences into account, including differences in support network and coping strategies. These findings demonstrate the need for improving awareness and knowledge about (J)VLS among HCPs, especially primary care providers, and among the general public.

The NLR SkinApp: Testing a Supporting mHealth Tool for Frontline Health Workers Performing Skin Screening in Ethiopia and Tanzania.

Background: The prevalence of skin diseases such as leprosy, and limited dermatological knowledge among frontline health workers (FHWs) in rural areas of Sub-Saharan Africa, led to the development of the NLR SkinApp: a mobile application (app) that supports FHWs to promptly diagnose and treat, or suspect and refer patients with skin diseases. The app includes common skin diseases, neglected tropical skin diseases (skin NTDs) such as leprosy, and HIV/AIDS-related skin conditions. This study aimed to test the supporting role of the NLR SkinApp by examining the diagnostic accuracy of its third edition. Methods: A cross-sectional study was conducted in East Hararghe, Ethiopia, as well as the Mwanza and Morogoro region, Tanzania, in 2018-2019. Diagnostic accuracy was measured against a diagnosis confirmed by two dermatologists/dermatological medical experts (reference standard) in terms of sensitivity, specificity, positive predictive value, and negative predictive value. The potential negative effect of an incorrect management recommendation was expressed on a scale of one to four. Results: A total of 443 patients with suspected skin conditions were included. The FHWs using the NLR SkinApp diagnosed 45% of the patients accurately. The values of the sensitivity of the FHWs using the NLR SkinApp in determining the correct diagnosis ranged from 23% for HIV/AIDS-related skin conditions to 76.9% for eczema, and the specificity from 69.6% for eczema to 99.3% for tinea capitis/corporis. The inter-rater reliability among the FHWs for the diagnoses made, expressed as the percent agreement, was 58% compared to 96% among the dermatologists. Of the management recommendations given on the basis of incorrect diagnoses, around one-third could have a potential negative effect. Conclusions: The results for diagnosing eczema are encouraging, demonstrating the potential contribution of the NLR SkinApp to dermatological and leprosy care by FHWs. Further studies with a bigger sample size and comparing FHWs with and without using the NLR SkinApp are needed to obtain a better understanding of the added value of the NLR SkinApp as a mobile health (mHealth) tool in supporting FHWs to diagnose and treat skin diseases.

Dermatoscopy and Optical Coherence Tomography in Vulvar High-Grade Squamous Intraepithelial Lesions and Lichen Sclerosus: A Prospective Observational Trial.

OBJECTIVE: This study aimed to examine potential discriminatory characteristics of dermatoscopy and dynamic optical coherence tomography (D-OCT) on vulvar high-grade squamous intraepithelial lesions (vHSIL) and lichen sclerosus (LS) compared with healthy vulvar skin. METHODS: A prospective observational clinical trial was performed in 10 healthy volunteers, 5 vHSIL and 10 LS patients. Noninvasive imaging measurements using dermatoscopy and D-OCT were obtained at several time points, including lesional and nonlesional vulvar skin. Morphologic features of vHSIL and LS were compared with healthy controls. Epidermal thickness and blood flow were determined using D-OCT. Patients reported tolerability of each study procedure, including reference vulvar biopsies. The main outcome measures were feasibility and tolerability of imaging modalities, dermatoscopy and OCT characteristics, OCT epidermal thickness and D-OCT dermal blood flow. RESULTS: The application of dermatoscopy and D-OCT is feasible and tolerable. In vHSIL, dermatoscopic warty structures were present. In LS, sclerotic areas and arborizing vessels were observed. Structural OCT in the vulvar area aligned with histology for hyperkeratosis and dermal-epidermal junction visualization. Currently, the OCT algorithm is unable to calculate the epidermal thickness of the uneven vulvar area. Dynamic optical coherence tomography showed statistically significant increased blood flow in LS patients (mean ± SD, 0.053 ± 0.029) to healthy controls (0.040 ± 0.012; p = .0024). CONCLUSIONS: The application of dermatoscopy and D-OCT is feasible and tolerable in vHSIL and LS patients. Using dermatoscopy and D-OCT, the authors describe potential characteristics to aid differentiation of diseased from healthy vulvar skin, which could complement clinical assessments.

The Paget Trial: topical 5% imiquimod cream for noninvasive vulvar Paget disease.

BACKGROUND: Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. Most vulvar Paget disease cases are noninvasive; however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for noninvasive vulvar Paget disease is wide local excision, which is challenging because of extensive intraepithelial spread and may cause severe morbidity. Recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. Imiquimod, a topical immune response modifier, has been shown to be effective in a few studies and case reports, and is a promising new treatment modality. OBJECTIVE: To prospectively investigate the efficacy, safety, and effect on quality of life of a standardized treatment schedule with 5% imiquimod cream in patients with noninvasive vulvar Paget disease. STUDY DESIGN: The Paget Trial is a multicenter prospective observational clinical study including 7 tertiary referral hospitals in the Netherlands. A total of 24 patients with noninvasive vulvar Paget disease were treated with topical 5% imiquimod cream 3 times a week for 16 weeks. The primary efficacy outcome was the reduction in lesion size at 12 weeks after the end of treatment. Secondary outcomes were safety, clinical response after 1 year, and quality of life. Safety was assessed by evaluation of adverse events and tolerability of treatment. Quality of life was investigated with 3 questionnaires taken before, during, and after treatment. RESULTS: Data were available for 23 patients, 82.6% of whom responded to therapy. A complete response was reported in 12 patients (52.2%), and 7 patients (30.4%) had a partial response. A histologic complete response was observed in 10 of the 12 patients with a complete response. Patients experienced side effects such as fatigue (66.7%-70.9%) and headaches (16.7%-45.8%), and almost 80% needed painkillers during treatment. Eight patients (34.8%) adjusted the treatment protocol to 2 applications a week, and 3 patients (13.0%) stopped treatment because of side effects after 4 to 11 weeks. Treatment improved quality of life, whereas a slight, temporary negative impact was observed during treatment. Two patients with a complete response developed a recurrence within 1 year after treatment. Follow-up showed 6 patients with a noninvasive recurrence after a median of 31 months (14-46 months) after the end of treatment. CONCLUSION: Topical 5% imiquimod cream can be an effective and safe treatment alternative for noninvasive vulvar Paget disease, particularly when compared with treatment with surgical excision.

Comparison of lichen sclerosus in boys and girls: A systematic literature review of epidemiology, symptoms, genetic background, risk factors, treatment, and prognosis.

BACKGROUND: Studies concerning pediatric lichen sclerosus are limited, and, to date, there have been no studies comparing the course of lichen sclerosus in boys and girls. We sought to examine all publications on boys and girls with lichen sclerosus and assess and compare epidemiology, symptoms and signs, genetic background, risk factors, treatment, and prognosis. METHODS: A systematic search was performed in the Embase, Medline, Cochrane, and Web of Science databases. Inclusion criteria were information on children ages 0-18 years and a clinical or histologic diagnosis of lichen sclerosus. Literature from 1985 to 2021 was reviewed. RESULTS: A total of 1780 articles were retrieved from the search, of which 90 articles were eligible for inclusion. Boys and girls present similarly on many aspects; nonetheless, treatment and follow-up are approached differently. CONCLUSIONS: Though the clinical approach is often different, lichen sclerosus in boys and girls demonstrates many similarities. More research is needed, especially on follow-up, to gain a better understanding of the course of lichen sclerosus and establish an advanced management plan for children.

Treatment and Outcome of Culture-Confirmed Mycobacterium marinum Disease.

Background: Mycobacterium marinum is a nontuberculous mycobacterium that causes skin and soft tissue infections. Treatment consists of multiple antibiotics, sometimes combined with surgical debridement. There is little evidence for the choice of antibiotics, the duration of treatment, and the role of susceptibility testing. Methods: We performed a retrospective cohort study of culture-confirmed M. marinum infections in the Netherlands in the 2011-2018 period. Clinical characteristics, in vitro susceptibility, extent of disease, treatment regimens, and outcomes were analyzed. Incidence was assessed from laboratory databases. Results: Forty cases of M. marinum infection could be studied. Antibiotic treatment cured 36/40 patients (90%) after a mean treatment duration of 25 weeks. Failure/relapse occurred in 3 patients, and 1 patient was lost to follow-up. Antibiotic treatment consisted of monotherapy in 35% and 2-drug therapy in 63%. Final treatment contained mostly ethambutol-macrolide combinations (35%). Eleven patients (28%) received additional surgery. We recorded high rates of in vitro resistance to tetracyclines (36% of isolates). Tetracycline resistance seemed correlated with poor response to tetracycline monotherapy. The annual incidence rate was 0.15/100 000/year during the study period. Conclusions: Prolonged and susceptibility-guided treatment results in a 90% cure rate in M. marinum disease. Two-drug regimens of ethambutol and a macrolide are effective for moderately severe infections. Tetracycline monotherapy in limited disease should be used vigilantly, preferably with proven in vitro susceptibility.

Fingerstick test quantifying humoral and cellular biomarkers indicative for M. leprae infection.

OBJECTIVES: New user-friendly diagnostic tests for detection of individuals infected by Mycobacterium leprae (M. leprae), the causative pathogen of leprosy, can help guide therapeutic and prophylactic treatment, thus positively contributing to clinical outcome and reduction of transmission. To facilitate point-of-care testing without the presence of phlebotomists, the use of fingerstick blood (FSB) rather than whole blood-derived serum is preferred. This study is a first proof-of-principle validating that previously described rapid serum tests detecting antibodies and cytokines can also be used with FSB. METHODS: Quantitative detection of previously identified biomarkers for leprosy and M. leprae infection, anti-M. leprae PGL-I IgM antibodies (αPGL-I), IP-10 and CRP, was performed with lateral flow (LF) strips utilizing luminescent up-converting reporter particles (UCP) and a portable reader generating unbiased read-outs. Precise amounts of FSB samples were collected using disposable heparinized capillaries. Biomarker levels in paired FSB and serum samples were determined using UCP-LF test strips for leprosy patients and controls in Bangladesh, Brazil, South-Africa and the Netherlands. RESULTS: Correlations between serum and FSB from the same individuals for αPGL-I, CRP and IP-10 were highly significant (p < .0001) even after FSB samples had been frozen. The αPGL-I FSB test was able to correctly identify all multibacillary leprosy patients presenting a good quantitative correlation with the bacterial index. CONCLUSIONS: Reader-assisted, quantitative UCP-LF tests for the detection of humoral and cellular biomarkers for M. leprae infection, are compatible with FSB. This allows near-patient testing for M. leprae infection and immunomonitoring of treatment without highly trained staff. On site availability of test-result concedes immediate initiation of appropriate counselling and treatment. Alternatively, the UCP-LF format allows frozen storage of FSB samples compatible with deferred testing in central laboratories.

WhatsApp platforms in tropical public health resource-poor settings.

In order to deliver equal healthcare access to resource-poor settings, sustainable, cost-effective systems of communication should be used. As mobile phone use increases, remote care can be delivered via teledermatology using Apps. This commentary covers how WhatsApp could be used by dermatologists seeking to deliver healthcare in this context.

The Development of a Mobile Application to Support Peripheral Health Workers to Diagnose and Treat People with Skin Diseases in Resource-Poor Settings.

The high prevalence of skin diseases in resource-poor settings, where health workers with sufficient knowledge of skin diseases are scarce, calls for innovative measures. Timely diagnosis and treatment of skin diseases, especially neglected tropical diseases (NTDs) that manifest with skin lesions, such as leprosy, is crucial to prevent disabilities as well as psychological and socioeconomic problems. Innovative technological methods like telemedicine and mobile health (mHealth) can help to bridge the gap between the burden of skin diseases and the lack of capable staff in resource-poor settings by bringing essential health services from central level closer to peripheral levels. Netherlands Leprosy Relief (NLR) has developed a mobile phone application called the 'SkinApp', which aims to support peripheral health workers to recognize the early signs and symptoms of skin diseases, including skin NTDs, and to start treatment promptly or refer for more advanced diagnostic testing or disease management when needed. Further research is needed to determine how greatly mHealth in general and the SkinApp in particular can contribute to improved health outcomes, efficiency, and cost-effectiveness.

The Paget Trial: A Multicenter, Observational Cohort Intervention Study for the Clinical Efficacy, Safety, and Immunological Response of Topical 5% Imiquimod Cream for Vulvar Paget Disease.

BACKGROUND: Vulvar Paget disease is a rare skin disorder, which is most common in postmenopausal Caucasian women. They usually present with an erythematous plaque that may show fine or typical "cake icing" scaling or ulceration that may cause itching, pain, irritation, or a burning sensation. Although most cases are noninvasive, vulvar Paget disease may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The histological evidence of so-called "Paget cells" with abundant pale cytoplasm in the epithelium confirms the diagnosis. The origin of these Paget cells is still unclear. Treatment of choice is wide local excision with negative margins. Obtaining clear surgical margins is challenging and may lead to extensive and mutilating surgery. Even then, recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. A number of case reports, retrospective case series, and one observational study have shown promising results using the topical immune response modifier imiquimod. OBJECTIVE: This study aims to investigate the efficacy, safety, and immunological response in patients with noninvasive vulvar Paget disease using a standardized treatment schedule with 5% imiquimod cream. METHODS: Topical 5% imiquimod cream might be an effective and safe treatment alternative for vulvar Paget disease. The Paget Trial is a multicenter observational cohort study including eight tertiary referral hospitals in the Netherlands. It is ethically approved by the Medical-Ethical Committee of Arnhem-Nijmegen and registered in the Central Committee on Research Involving Human Subjects (CCMO) Register by as NL51648.091.14. Twenty patients with (recurrent) noninvasive vulvar Paget disease will be treated with topical 5% imiquimod cream three times a week for 16 weeks. The primary efficacy outcome is the reduction in lesion size at 12 weeks after end of treatment. Secondary outcomes are safety, immunological response, and quality of life. Safety will be assessed by evaluation of adverse events and tolerability of treatment. To evaluate the immunological response, various immunological markers will be tested on biopsy specimens taken before, during, and after treatment. Quality of life will be assessed with three questionnaires taken before, during, and after treatment. RESULTS: First results are expected in the summer of 2018. TRIAL REGISTRATION: ClinicalTrials.gov NCT02385188; https://clinicaltrials.gov/ct2/show/NCT02385188 (Archived by WebCite at http://www.webcitation.org/6sXygHuhP).

Soil-transmitted helminth infections and leprosy: a cross-sectional study of the association between two major neglected tropical diseases in Indonesia.

BACKGROUND: The clinical spectrum of leprosy is dependent on the host immune response against Mycobacterium leprae or the newly discovered Mycobacterium lepromatosis antigen. Helminth infections have been shown to affect the development of several diseases through immune regulation and thus may play a role in the clinical manifestations of leprosy and leprosy reactions. The purpose of this study is to determine the proportion of helminth infections in leprosy and its association with the type of leprosy and type 2 leprosy reaction (T2R). METHODS: History or episode of T2R was obtained and direct smear, formalin-ether sedimentation technique, and Kato-Katz smear were performed on 20 paucibacillary (PB) and 61 multibacillary (MB) leprosy participants. RESULTS: There are more helminth-positive participants in MB leprosy compared to PB (11/61 versus 0/20, p = 0.034) and in T2R participants compared to non-T2R (8/31 versus 3/50, p = 0.018). CONCLUSIONS: Our results suggest that soil-transmitted helminth infections may have a role in the progression to a more severe type of leprosy, as well as the occurrence of T2R. These findings could serve as a fundamental base for clinicians to perform parasitological feces examination in patients who have MB leprosy and severe recurrent reactions to rule out the possibility of helminth infection. Further secondary confirmation of findings are needed to support these conclusions.

Leprosy type 1 reaction (formerly reversal reaction).

Nerve damage leading to impairment and permanent disability is the major problem in the course of a leprosy infection. Most of the damage occurs during two types of leprosy reactions, type 1 reaction (T1R) and type 2 reaction (T2R). Timely and adequate treatment may prevent this damage. Particular T1R reactions, however, are often diagnosed too late and are even missed. Clinical symptoms and warning signs are therefore covered, as are the immunology and pathophysiology of nerve damage. The differences between upgrading and downgrading, old terms but still relevant, are explained. Methods to detect reactions and to monitor their treatment are given. Triggering factors, the mechanisms of the reactions, including autoimmunity, and the presence of physical compression are discussed. Treatment over the years is placed in its context, and based on this information a treatment schedule is recommended.

[A boy with an unexpected souvenir from Morocco]. / Een jongen met een onverwacht souvenir uit Marokko.

A 12-year-old boy returned from a summer holiday in North Morocco with a slowly progressive erythematous, infiltrated plaque with a central crust on his right cheek. We diagnosed this as cutaneous leishmaniasis. Treatment for Leishmania major infection failed; subsequent PCR species typing revealed Leishmania infantum. This case shows the importance of recognition of parasitic skin diseases in travellers to the nearby subtropics and the value of leishmania species typing.

Longitudinal immune responses and gene expression profiles in type 1 leprosy reactions.

PURPOSE: Leprosy, a chronic disease initiated by Mycobacterium leprae, is often complicated by acute inflammatory reactions. Although such episodes occur in at least 50% of all leprosy patients and may cause irreversible nerve damage, no laboratory tests are available for early diagnosis or prediction of reactions. Since immune- and genetic host factors are critical in leprosy reactions, we hypothesize that identification of host-derived biomarkers correlated to leprosy reactions can provide the basis for new tests to facilitate timely diagnosis and treatment thereby helping to prevent tissue damage. METHODS: The longitudinal host response of a leprosy patient, who was affected by a type 1 reaction (T1R) after MDT-treatment, was studied in unprecedented detail, measuring cellular and humoral immunity and gene expression profiles to identify biomarkers specific for T1R. RESULTS: Cytokine analysis in response to M. leprae revealed increased production of IFN-γ, IP-10, CXCL9, IL-17A and VEGF at diagnosis of T1R compared to before T1R, whereas a simultaneous decrease in IL-10 and G-CSF was observed at T1R. Cytokines shifts coincided with a reduction in known regulatory CD39(+)CCL4(+) and CD25(high) T-cell subsets. Moreover, RNA expression profiles revealed that IFN-induced genes, (V)EGF, and genes associated with cytotoxic T-cell responses (GNLY, GZMA/B, PRF1) were upregulated during T1R, whereas expression of T-cell regulation-associated genes were decreased. CONCLUSIONS: These data show that increased inflammation, vasculoneogenesis and cytotoxicity, perturbed T-cell regulation as well as IFN-induced genes play an important role in T1R and provide potential T1R-specific host biomarkers.