Global epidemiology and disparities in atopic dermatitis.

Atopic dermatitis (AD) affects children and adults worldwide. Advancements have been made towards unravelling the pathogenesis of AD, identifying various triggers, linking the environment and psychosocial factors with disease and the development of therapeutic targets to improve disease control. This article describes the global epidemiology of AD and the disparities that exist in various populations and regions across the globe. AD prevalence and burden varies widely both within and between countries inhabited by the same ethnic groups, which suggests strong environmental influences in disease expression, with socioeconomic status and affluence considered to be the main driving factors. Inequities in access to healthcare, and the quality of healthcare provided, among racial and ethnic minority groups are well documented. Disparities in access to various topical and systemic therapies are affected by barriers to registration and approval, cost, manufacturing, supply and approval by medical insurance companies and governments. Identifying the factors driving the inequities in access to healthcare is central to achieving better patient care.

Selective serotonin reuptake inhibitor and serotonin-norepinephrine reuptake inhibitor associated cutaneous adverse drug reactions: A systematic review of case reports and case series.

Anecdotal evidence suggests that selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) cause cutaneous adverse drug reactions (CADRs). However, there is limited information on the factors associated with these occurrences. In this study, we aimed to describe the demographic, clinical and pharmacological characteristics associated with CADRs encountered by patients administered SSRIs and/or SNRIs for psychiatric diagnoses and to compare the differences in these factors between severe and non-severe CADRs. A protocol was developed a priori (PROSPERO: CRD42020204830) in line with the PRISMA guidelines. We searched PubMed/Medline, PsycINFO and SCOPUS from inception to October 2020 to identify case reports and/or case series of SSRI and SNRI associated CADRs. Additional cases were obtained from the retrieved articles' bibliography. A total of 141 articles were included in the study, documenting 173 CADRs. Females accounted for 128 (74.0%) of the analysed CADRs. The median age of the cases was 42 IQR (27; 53) with no statistically significant differences in age between males and females (P = 0.542). A total of 157 (90.8%) of the reported CADRs were associated with SSRIs, particularly fluoxetine 68 (39.5%), sertraline 30 (17.4%) and paroxetine 25 (14.5%). Non-severe CADRs and severe CADRs accounted for 23 (13.4%) and 149 (86.6%) reports respectively. No statistically significant differences were observed for gender (P = 0.616), age at onset (P = 0.493) and time to onset (P = 0.105) between non-severe CADRs and SCARs. In conclusion, CADRs following SSRIs and SNRIs disproportionately affect females in the reproductive age group compared to males and are mostly associated with SSRIs.

Concurrent pulmonary tuberculosis and lepromatous leprosy in a newly diagnosed HIV positive patient: a case report.

BACKGROUND: The leprosy-tuberculosis (TB) co-infection is rarely reported in recent times. However, this dual comorbidity is associated with high mortality and major morbidity. Unrecognised leprosy-TB co-infection may predispose affected patients to rifampicin monotherapy and subsequent drug resistance. CASE PRESENTATION: A 35 year old migrant, human immunodeficiency virus (HIV) positive male worker presented with 6 month history of symmetric infiltrative nodular plaques of the face and distal, upper extremities. A few days after initial dermatology presentation, a sputum positive pulmonary tuberculosis diagnosis was made at his base hospital. Subsequent dermatology investigations revealed histology confirmed lepromatous leprosy and a weakly reactive rapid plasma reagin test. The presenting clinical features and laboratory results were suggestive of lepromatous leprosy coexisting with pulmonary tuberculosis in an HIV positive patient. CONCLUSIONS: This case illustrates the occurrence of leprosy with pulmonary tuberculosis in an HIV infected patient and the difficulties in interpreting non-treponemal syphilis tests in these patients. This case also highlights the need for a high index of suspicion for co-infection and the need to exclude PTB prior to initiation of rifampicin containing multi-drug therapy (MDT). Interdisciplinary management and social support are crucial in these patients.

Epidermal barrier function in healthy black South African infants compared with adults.

A cross-sectional observational study of 43 infants and 60 adult women was performed in South Africa to assess skin barrier (SB) function through noninvasive quantification of transepidermal water loss (TEWL) and skin surface hydration (SSH). TEWL and SSH improved with age and in anatomic locations with chronic environmental exposure in keeping with reported trends in other ethnicities.

HIV infection predisposes skin to toxic epidermal necrolysis via depletion of skin-directed CD4⁺ T cells.

BACKGROUND: A greater incidence of adverse cutaneous drug eruptions, including toxic epidermal necrolysis (TEN), occurs among HIV-infected patients. OBJECTIVE: We sought to determine if immunophenotypical differences exist in the inflammatory infiltrates of TEN lesions from HIV-infected individuals versus noninfected individuals. METHODS: The inflammatory infiltrates in 12 cases of TEN from HIV-positive patients were characterized and compared with the infiltrates present in 12 cases of TEN from HIV-negative patients. RESULTS: TEN infiltrates consisted of CD3, CD4, and CD8 immunoreactive T lymphocytes in both the dermis and epidermis. HIV infection was associated with an 8-fold increase in the ratio of CD8(+) to CD4(+) T cells infiltrating the dermis (P = .006) and a decrease in the number of dermal CD4(+) cells (P = .044). There was also a significant decrease in the ratio of CD25(+) to CD4(+) cells in the epidermis of HIV-infected skin (P = .011). LIMITATIONS: This study is limited by small sample sizes. CONCLUSION: A decrease in the number of skin-directed CD4(+) cells and an increase in the ratio of CD8(+) to CD4(+) cells exists in TEN lesions among HIV-infected individuals and likely contribute to an increased risk of developing drug reactions because of the loss of skin-protective CD4(+)CD25(+) regulatory T cells.

The Prevalence of Clinically Undiagnosed Depression in Patients With Autoimmune Bullous Diseases Seen at Inkosi Albert Luthuli Central Hospital, Durban, South Africa.

Background Chronic autoimmune bullous diseases have been associated with major depression in previous studies. This has been attributed to inflammatory cytokines, chronic pain, and the chronicity and debilitating nature of the disease. As no similar studies have been conducted in our setting, we aimed to determine the prevalence and severity of clinically undiagnosed depression in patients with autoimmune bullous diseases. Methodology We performed a cross-sectional study among outpatients managed in a bullous disease clinic at Inkosi Albert Luthuli Central Hospital, a quaternary provincial hospital in Durban, South Africa. Results A total of 44 participants were recruited and included in this study. The majority of the participants were females (29, 65.9%). The most common autoimmune bullous diseases were pemphigus vulgaris (19, 43.2%), bullous pemphigoid (18, 40.9%), and pemphigus foliaceus (5, 11.4%). The overall prevalence of at least mild and at least moderate depression in patients with autoimmune bullous diseases in our clinic was 52.3% and 20.5%, respectively. Pemphigus vulgaris showed the highest median Patient Health Questionnaire-9 score compared to other bullous dermatoses. Statistically significant differences were observed between females and males for the duration with the bullous disease (p = 0.014) and between intraepidermal and subepidermal disease for both the mean age (p = 0.038) and age at onset (p = 0.015). Conclusions Clinically undiagnosed depression is common in patients with autoimmune bullous disease. Its frequency and severity may differ depending on the underlying autoimmune bullous disease and possibly other factors. Dermatologists should always be alert to this fact and prompt psychiatric consultation as required to comprehensively manage these patients.

Importance of clinico-pathologic correlation in rare, chronic infectious diseases: Actinomycetoma misdiagnosed as botryomycosis-A case report.

This case report explores the clinical journey of a patient initially diagnosed with botryomycosis, only to later reveal the underlying and rare condition of actinomycosis. The report highlights the challenges in getting to an accurate diagnosis, emphasizing the importance of considering uncommon pathologies, the utility of multi-disciplinary teams and clinico-pathologic correlation in clinical practice.

Human T cell lymphotropic virus type 1- associated infective dermatitis in KwaZulu Natal, South Africa.

BACKGROUND: The Human T cell lymphotropic virus type 1 (HTLV-1)-associated infective dermatitis (IDH), is a chronic relapsing dermatitis which usually presents in children older than 2 years. A total of 300 cases have been reported worldwide (Latin America, the Caribbean and only 5 from Senegal). Neither IDH, nor its complications have been reported from the rest of Africa. We aimed to examine the clinical and aetiological characteristics of IDH in a cohort of South African children. METHODS: Attendees at the dermatology clinic at King Edward VIII Hospital, Durban underwent clinical examination. After obtaining consent those suspected of IDH had specimens taken for blood counts, immunoglobulins, serum protein electrophoresis, viral studies (including genotyping), skin swabs and stool examinations. RESULTS: Nineteen of 60 suspected cases recruited over 3 years met the diagnostic criteria for IDH. The male-to-female ratio was 1:2; mean age 8 years (range 0.7 to 15). Dermatitis mostly affected the scalp (78.9%) and axilla (73.7%); fewer children had nasal crusting (47.4%). Mean Ig A, IgG and IgM were raised, at 3.52 g/l, 22.6 g/l and 1.38 g/l, respectively. The median CD4 cell count was 1958 cells/mm3. Viral genotyping of all tested samples were positive for the Cosmopolitan, Subtype A (HTLV-1a). CONCLUSIONS: IDH is a distinct entity which also affects South Africans. Our patients were older at presentation and the majority did not present with nasal crusting as has been described in other countries.

Epidermal barrier function in human immunodeficiency virus-infected South African infants compared with uninfected.

BACKGROUND AND OBJECTIVE: Infant human immunodeficiency virus (HIV) infection remains a problem in different parts of the world. Early signs of disease manifestation often involve infant skin. This study compared the skin barrier properties of HIV infected with uninfected infants. METHODS: A cross-sectional descriptive study was undertaken with HIV positive and HIV negative unexposed African infants (6 weeks-12 months). Both had normal birth weight for age, no pre-existing dermatoses or co-infections, and received all their vaccinations timeously. The HIV positive infants were on antiretroviral (ARV) therapy. The skin barrier quality was assessed by measuring the transepidermal water loss (TEWL) and skin surface hydration (SSH) on the dorsal arm (1) and the inner forearm (2). RESULTS: Eighty-six HIV negative and 43 HIV positive African children were recruited. There were significant differences between the two groups based on the presence of HIV infection. In both sites, measured TEWL rates were significantly higher for the HIV positive children. There was a nonsignificant difference between the SSH values for site 1 and a marginally significant difference for site 2, with the average values higher in the HIV positive group. In both groups, TEWL rates and SSH values were significantly lower on site 1 compared to site 2. CONCLUSION: Differences in skin barrier properties of HIV infected and uninfected children may exist. The altered skin barrier in infected children may be one of the factors that predisposes them to various inflammatory and infectious dermatoses. Improving the skin barrier may assist in preventing these conditions.

Microbiologic characterisation of bacterial infections in children with atopic dermatitis.

Background: Patients with atopic dermatitis (AD), the commonest chronic inflammatory skin disease are often colonised and infected by Staphylococcus aureus. In this study, we aimed to determine the type and antibacterial sensitivities of the bacteria infecting eczematous lesions in children with AD and to recommend first-line antibiotic therapy. Methods: A prospective study was conducted from June 2020 to June 2021 in children with AD presenting with a cutaneous infection at the King Edward hospital VIII outpatient dermatology clinic. Swabs were collected for microbial culture, confirming infections and assessing antibiotic sensitivity for infected sites. Results: Ninety six children were recruited during the study period with a mean age of 4.3 ± 3.4 years. The commonest cause of bacterial infection was Staphylococcus aureus seen in 74 (77.1%) cases, followed by Staphylococcus aureus and Group A ß-haemolytic streptococcus (GAS) co-infection in 22 (22.9%) cases. The majority of these infections were observed on the lower limbs in 50 (52.08%) cases and in moderate 37 (38.5%) cases and severe eczema cases of 38 (39.6%) in AD. There was no gender predilection. Staphylococcus aureus was sensitive to amoxicillin-clavulanic acid in 57 (77.0%) cases, cloxacillin in 53 (71.6%) cases and clindamycin in 24 (32.4%) cases, whereas GAS was mostly sensitive to ampicillin in 10 (45.5%) cases. No swabs retained a resistant strain. Conclusion: Staphylococcus aureus is the commonest bacterial cause of cutaneous infection in children with AD in our setting. Amoxicillin-clavulanic acid and cloxacillin remain the most sensitive therapeutic options for this infection, however, a larger study is required to explore resistance strains, if any, in our setting.

Mapping research evidence on quality of life in children with atopic dermatitis in sub-Saharan Africa: a scoping review protocol.

BACKGROUND: Atopic dermatitis (AD) is a chronic, debilitating disease affecting children worldwide. Several studies have shown the disease to be a significant problem which leads to a diminished quality of life (QoL) for the affected children, but systematic evaluation of such studies in Africa is yet to be reported. Therefore, this scoping review aims to map research evidence on children with AD and their QoL in sub-Saharan Africa (SSA). METHODS: The scoping review will follow the Arksey and O'Mally methodological framework. The electronic databases to be searched will include PubMed, EBSCOhost (Academic Search Complete, CINAHL, PsycINFO, and Health Sources), and Scopus and Google Scholar, for published literature between 2010 and 2021. The search strategy for the databases will include keywords, Medical Subject Headings terms, and Boolean operators. The reference list of the included sources of evidence and the WHO website will also be consulted for evidence relating to QoL of children with AD in SSA. Two independent reviewers will undertake abstract and full-text article screening with the guidance of eligibility criteria. This review will include studies conducted in SSA, and publications focusing on QoL and associated factors of AD in children. Data will be extracted from the included studies and analyzed qualitatively; NVIVO software V.11 will be used, and the emerging themes reported narratively. The mixed-method appraisal tool (MMAT) will be employed for quality appraisal of included studies. DISCUSSION: We look forward to the findings of several studies that describe the QoL and associated factors among children with AD and that report on the use of different diagnostic criteria, severity scaling and QoL measuring scale tools used to ascertain the presence of AD, scale the severity of AD, and the impact of AD on QoL among children. This will help to improve clinical practice and the QoL of children with AD in SSA. The study findings will be disseminated through publication in a peer-reviewed journal, peer presentations, and presentations at relevant conferences. CONCLUSION: This study will add new knowledge on the QoL in children with AD in the SSA context. The study has the potential to inform research and clinical practice to impact the QoL of children with AD in SSA.

Mucocutaneous diseases in the combined antiretroviral therapy era: prevalence and spectrum in HIV seropositive children and adolescents in Durban, South Africa.

BACKGROUND: Mucocutaneous diseases (MCD) have been commonly described among human immunodeficiency virus (HIV) infected patients before the combined antiretroviral therapy (cART) era. There is limited data on the frequency and type of MCD in the cART era in African children and adolescents. This study aimed to describe the prevalence and spectrum of MCD in South African children and adolescents seropositive for HIV on cART. METHODS: A cross-sectional study of 310 participants aged 0-19 years attending a public sector ART clinic at King Edward VIII Hospital, Durban, South Africa, was conducted. Demographic, clinical, and laboratory information was obtained from the participants and hospital records. Participants were examined. Data were collated and analyzed with SPSS version 23. RESULTS: MCD were observed in 77.4% of HIV-infected children. The prevalence was higher among males and adolescents above 16 years old (83.9%). Infectious skin disorders (44.7%) were less common than noninfectious dermatoses (55.3%). More common disorders encountered included generalized pruritus (32.6%), fungal infections (20.9%), and inflammatory (20.4%) and pigmentary (20.4%) skin disorders. Tinea capitis and pedis were the most prevalent fungal infections, while oral candidiasis (0.2%) was the least. Inflammatory skin disorders and dyschromia appeared to be more common than in the pre-cART era. CONCLUSIONS: While MCD are still common in HIV-infected children and adolescents in the cART era, the pattern and types of disorders have changed to a predominance of non-infectious dermatoses.

Dermatology Training in Africa: Successes and Challenges.

This article analyzes various dermatology training programs in Africa by region and country. There is a paucity of dermatologists for the African population. West Africa has a harmonized curriculum, adopted by some anglophone and most francophone countries in the region. Algeria, Egypt, Ethiopia, Morocco, South Africa, Sudan, Tanzania, and Tunisia have national curricula. In the remaining countries for which information is available and programs exist, a university-specific curriculum is followed. Of the 55 countries in Africa, there is no opportunity for dermatology specialization in 30. Local and ethnic skin curricula content appropriate for Africa, developed through continent-wide collaborations, are recommended.

The impact of basic dermatology education and training on primary healthcare providers in KwaZulu-Natal, South Africa.

BACKGROUND: Dermatological diseases are amongst the commonest reasons for consultation at primary care level. Yet, dermatology teaching in medical and nursing curricula is inconsistent and often insufficient to enable medical and nursing professionals to manage these conditions effectively. METHODS: We tested the knowledge of 100 doctors and 195 nurses who attended dermatology training sessions held in three health districts in the province of KwaZulu-Natal (KZN), South Africa, by using a quasi-experimental uncontrolled before-and-after study design. At the start of the session, participants were exposed to 15 slides representing common dermatological conditions; this was followed by a test. The participants then attended a series of short lectures followed by the same test. Pre- and post-intervention test scores were compared, and the results were analysed by professional status, health district and type of facility. RESULTS: The mean (standard deviation [SD]) pre-intervention test score was 40.6% (20.5%). Doctors scored significantly higher than nurses (p 0.0001). There were significant differences in performance by district (p 0.001) and type of facility (p 0.001). The mean (SD) post-intervention score improved to 68.7% (22.5%). CONCLUSION: Doctors and nurses working in the primary care sector appear to be insufficiently trained in the management of common dermatological conditions. A short period of in-service training resulted in an immediate, significant improvement in knowledge, although we did not study long-term retention beyond this. We recommend improved prequalification training in dermatology in medical and nursing schools and an expansion of continuing professional development as well as in-service training opportunities for primary care practitioners.

Substantial regional differences in human herpesvirus 8 seroprevalence in sub-Saharan Africa: insights on the origin of the "Kaposi's sarcoma belt".

Equatorial Africa has among the highest incidences of Kaposi's sarcoma (KS) in the world, thus earning the name "KS Belt." This was the case even before the HIV epidemic. To date, there is no clear evidence that HHV-8 seroprevalence is higher in this region but interpretation of the available literature is tempered by differences in serologic assays used across studies. We examined representatively sampled ambulatory adults in Uganda, which is in the "KS Belt," and in Zimbabwe and South Africa which are outside the Belt, for HHV-8 antibodies. All serologic assays were uniformly performed in the same reference laboratory by the same personnel. In the base-case serologic algorithm, seropositivity was defined by reactivity in an immunofluorescence assay or in 2 enzyme immunoassays. A total of 2,375 participants were examined. In Uganda, HHV-8 seroprevalence was high early in adulthood (35.5% by age 21) without significant change thereafter. In contrast, HHV-8 seroprevalence early in adulthood was lower in Zimbabwe and South Africa (13.7 and 10.8%, respectively) but increased with age. After age adjustment, Ugandans had 3.24-fold greater odds of being HHV-8 infected than South Africans (p < 0.001) and 2.22-fold greater odds than Zimbabweans (p < 0.001). Inferences were unchanged using all other serologic algorithms evaluated. In conclusion, HHV-8 infection is substantially more common in Uganda than in Zimbabwe and South Africa. These findings help to explain the high KS incidence in the "KS Belt" and underscore the importance of a uniform approach to HHV-8 antibody testing.

Defining immune reconstitution inflammatory syndrome: evaluation of expert opinion versus 2 case definitions in a South African cohort.

BACKGROUND: There is no validated case definition for human immunodeficiency virus-associated immune reconstitution inflammatory syndrome (IRIS). We measured the level of agreement of 2 published case definitions (hereafter referred to as CD1 and CD2) with expert opinion in a prospective cohort of patients who were starting antiretroviral therapy in South Africa. METHODS: A total of 498 adult patients were monitored for the first 6 months of antiretroviral therapy. All new or worsening clinical events were reviewed by 2 investigators and classified on the basis of expert opinion, CD1, and CD2. Events were categorized according to whether they were paradoxical or unmasking in presentation. We measured positive, negative, and chance-corrected agreement (kappa) with expert opinion for CD1 and CD2, and reviewed areas of disagreement. RESULTS: A total of 620 clinical events were recorded, of which, on the basis of expert opinion, 144 (23.2%) were defined as probable IRIS and 112 (18.1%) were defined as possible IRIS. Of the 144 probable IRIS events, 93 (64.6%) were unmasking in presentation, 99 (68.8%) were associated with dermatological or orogenital disease, and 45 (31.3%) were associated with tuberculosis or major opportunistic infections. Of the 620 clinical events recorded, 41 (6.6%) were classified as IRIS on the basis of CD1, and 156 (25.2%) were classified as IRIS on the basis of CD2. Positive agreement between CD1 and expert opinion was low for both unmasking (17.2%; kappa = 0.24) and paradoxical events (37.3%; kappa = 0.43), mainly because 1 major criterion requires IRIS to be atypical and either an opportunistic infection or a tumor, although negative agreement was >98%. In contrast, CD2 had good positive agreement (>75% for most event types), with a kappa value of 0.75 for paradoxical and 0.62 for unmasking. CONCLUSIONS: CD2 agreed well with expert opinion, with additional clinical events, such as arthropathy and inflammatory dermatoses, being classified as IRIS and added to CD2. We propose revised case definitions for both paradoxical and unmasking IRIS.

Lupus Masquerading as a Drug Reaction in HIV Infection.

An HIV-positive female on antiretroviral therapy (ART) presented with an annular eruption diagnosed as a drug reaction based on histology of a lichenoid dermatitis. She responded to oral steroid therapy and discontinuation, but progressed to develop features in keeping with cutaneous lupus. Although the antinuclear factor remained negative, her low serum complement levels, histology, and clinical features pointed to a diagnosis of subacute lupus in the setting of HIV infection. She responded well to antimalarial therapy and recommenced ART.