A Practical Guide to Using Oral JAK Inhibitors for Atopic Dermatitis from the International Eczema Council.

BACKGROUND: Janus kinase inhibitors (JAKinibs) have the potential to dramatically alter the landscape of atopic dermatitis (AD) management due to their promising efficacy results from phase 3 trials and rapid onset of action. However, JAKinibs are not without risk, and their use is not appropriate for all AD patients, making this a medication class that dermatologists should understand and consider when treating patients with moderate-to-severe AD. OBJECTIVE: This consensus expert opinion statement from the International Eczema Council (IEC) provides a pragmatic approach to prescribing JAKinibs, including choosing appropriate patients, dosing, clinical and lab monitoring, as well as long-term use. METHODS: An international cohort of authors from the IEC with expertise in JAKinibs selected topics of interest and were formed into authorship groups covering 10 subsections. The groups performed topic-specific literature reviews, consulted up-to-date adverse event (AE) data, referred to product labels and provided analysis and expert opinion. The manuscript guidance and recommendations were reviewed by all authors as well as the IEC Research Committee. RESULTS: We recommend JAKinibs be considered for patients with moderate to severe AD seeking the benefits of rapid reduction in disease burden and itch, oral administration, and the potential for flexible dosing. Baseline risk factors should be assessed prior to prescribing JAKinibs, including increasing age, venous thromboembolisms, malignancy, cardiovascular health, kidney/liver function, pregnancy and lactation, and immunocompetence. Patients being considered for JAKinib therapy should be current on vaccinations and we provide a generalized framework for laboratory monitoring, though clinicians should consult individual product labels for recommendations as there are variations among the JAKinib class. Patients who achieve disease control should be maintained on the lowest possible dose, as many of the observed AEs occurred in a dose-dependent manner. Future studies are needed in AD patients to assess the durability and safety of continuous long-term use of JAKinibs, combination medication regimens, and the effects of flexible, episodic treatment over time. CONCLUSIONS: The decision to initiate a JAKinib should be shared among patient and provider, accounting for AD severity and personal risk/benefit assessment, including consideration of baseline health risk factors, monitoring requirements and treatment costs.

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.

Synthetic hair extensions causing irritant contact dermatitis in patients with a history of atopy: A report of 10 cases.

BACKGROUND: We present a case series of 10, atopic, African women who developed irritant contact dermatitis (ICD) from synthetic hair extensions. METHODS: Ten consecutive African female patients who presented with a pruritic cutaneous eruption on the neck over a period of 2 years are described. Patients underwent skin patch testing using both standard and hair commercial patch test panels and samples of their own hair extensions. Hair care products were not tested. RESULTS: All 10 patients used synthetic hair extensions. A strong history of atopy was documented for all the patients and examination was significant for eczematous, lichenified plaques at the location of contact with the free end of the hair extension. Patch test results yielded no relevant reactivity and a diagnosis of ICD was made for all patients. The lesions resolved completely on removal of the hair extensions and the use of topical steroids and emollients, dependent on eczema severity. CONCLUSIONS: Artificial hair extensions should be considered as a potential irritant, resulting in ICD. Patients with a history of atopy are at risk of developing ICD from synthetic hair extensions.

Genetic diversity of HHV8 subtypes in South Africa: A5 subtype is associated with extensive disease in AIDS-KS.

Human herpes virus 8 (HHV8) is the etiological agent of all forms of Kaposi's sarcoma (KS). Six major subtypes (A-F), based on genetic variability of open reading frame (ORF)-K1, have been identified. Numerous studies point to differing tumorigenic and pathogenic properties of the HHV8 subtypes. The study objectives were to determine the HHV8 subtypes and their prevalence in a cohort of clinical and histologically confirmed KS in Cape Town, South Africa, and analyze associations between the different subtypes and clinical presentation of KS. Clinical records were prospectively reviewed to extract clinical presentation; demographic data were retrospectively collected and tissue biopsies were taken for ORF-K1 subtyping. Eighty six patients were subtyped; 81 AIDS (acquired immune deficiency syndrome)-KS and 5 African endemic-KS. Subtype A5 (42/86) and B2 (16/86) predominated. B1, B3, A1 and A4 subtypes were identified in 10/86, 9/86, 4/86 and 1/86 patients, respectively. A5 and B subtypes were found in African blacks and individuals of mixed ancestry, while subtypes A1 and A4 were found only in whites and individuals of mixed ancestry. Subtype A5 was associated with >10 KS lesions at presentation in the AIDS cohort (adjusted OR: 3.13; CI: 1.02-9.58). Subtypes A1 and A4 combined were less likely to be associated with poor risk tumor extension (P = 0.031) and A1 was associated with lower likelihood of lower limb involvement (P = 0.019). In conclusion, these results indicate that subtype A5 and B predominate in South Africa and A5 may be associated with more extensive disease.

Lack of cross-toxicity between isoniazid and ethionamide in severe cutaneous adverse drug reactions: a series of 25 consecutive confirmed cases.

BACKGROUND: Isoniazid and ethionamide are important first- and second-line anti-TB drugs (FLDs and SLDs), respectively. Ethionamide is a structural analogue of isoniazid and the two drugs share other similarities, including their metabolism, therapeutic targets, hepato-toxicity patterns and drug resistance. As a result, there has always been concern about possible cross-reactivity between them. METHODS: Among 69 patients with drug rash with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) to FLDs, FLDs were stopped and SLDs added when the skin and laboratory parameters had settled. This was followed by sequential and additive rechallenge with FLDs. We report 25 consecutive cases that developed confirmed cutaneous adverse drug reactions (CADRs) to isoniazid or ethionamide used as FLD and SLD, respectively. RESULTS: Sixty-nine participants who developed CADRs on FLDs were enrolled in the study. Twenty developed a rechallenge reaction to isoniazid and five reacted to ethionamide. Four of the 20 isoniazid cases were patch test positive, 3/20 were skin prick test positive and 13/20 reacted to oral rechallenge. All seven cases that were patch and skin prick test positive were associated with systemic reactions. Twenty of the 25 cases had DRESS and 5 had SJS/TEN. Twenty-three of the 25 cases with rechallenge reactions were HIV infected. Importantly, none of the cases that reacted to ethionamide during the rechallenge reacted to isoniazid and none who subsequently reacted to isoniazid reacted to ethionamide. CONCLUSIONS: Our findings strongly suggest that the risk of cross-reactivity of isoniazid and ethionamide in DRESS syndrome and SJS/TEN is low. These findings have implications for clinical management.

A comprehensive pathophysiology of dandruff and seborrheic dermatitis - towards a more precise definition of scalp health.

Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published literature from in vivo studies of D/SD populations to provide a more complete description of overall scalp health. New biomolecular capabilities establish a depth of pathophysiological understanding not previously achievable with traditional means of investigation. Biomarkers representing inflammation, hyper-proliferation and barrier function are all perturbed by the D/SD condition and robustly respond to therapeutic resolution. These biomarkers can be sampled noninvasively, enabling their use in routine clinical evaluations as either surrogate endpoints or complementary ones to classical signs/symptoms to broaden the etiological learning.

Dermatological diagnostic acumen improves with use of a simple telemedicine system for underserved areas of South Africa.

OBJECTIVE: Telemedicine holds promise as a tool for improving the delivery of specialty care, especially in underserved regions, including those in South Africa. However, data that demonstrate the extent of its sustainable benefits to referring providers are currently insufficient. This study investigates whether utilization of a teledermatology network enhances the diagnostic acumen of primary care providers (PCPs) in underserved areas of South Africa. MATERIALS AND METHODS: A longitudinal descriptive pilot study was conducted after establishing a telemedicine network linking University of Cape Town dermatology consultants to six providers from five underserved primary care sites using store-and-forward technology between October 2004 and January 2007. Of 120 total referrals, trend analysis was performed using 72 sets of patient histories, digital images, and corresponding consultant responses to evaluate the diagnostic concordance between six PCPs and teleconsultants over 12 consecutive referrals. RESULTS: Strong positive Spearman rank-order correlations were observed between the number of referrals sent per PCP and proportion of primary diagnostic agreement with teledermatologists, rs=0.86 (p <0.001). The mean primary diagnostic concordance trend that started at 13% for the first four referrals increased nearly fourfold after referring as few as nine patients to the network. CONCLUSIONS: If a simple and inexpensive teledermatology solution is carefully implemented in a resource-limited setting, an improvement of PCP diagnostic acumen can be achieved with a relatively small number of referrals. This educational benefit to referring PCPs could be sustainable and would ultimately enhance the quality of dermatological care in these underserved regions.

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.

A double-blind, randomized, placebo-controlled, dose-finding study of oral pramiconazole in the treatment of pityriasis versicolor.

BACKGROUND: Pramiconazole is a broad-spectrum triazole antifungal with potential for oral treatment of pityriasis versicolor. OBJECTIVE: We sought to assess the efficacy and tolerability of 5 doses of pramiconazole relative to placebo. METHODS: This was a randomized, multicenter, double-blind, placebo-controlled, 28-day, dose-finding study. A total of 147 patients were randomized to treatment with placebo or one of 5 doses of pramiconazole; treatment lasted for 3 consecutive days. Efficacy was based on mycological response, severity of clinical signs and symptoms, and the Investigator Global Assessment of lesion clearance. RESULTS: A statistically significant (P < .001) dose-dependent effect was observed. When compared with placebo, a significant response (P < .05) was obtained for all but the lowest single dose of pramiconazole. There were no serious, treatment-related adverse events or other safety concerns. LIMITATIONS: The follow-up period was limited to 1 month after treatment onset. CONCLUSIONS: Pramiconazole is a well-tolerated and effective treatment for pityriasis versicolor and the most effective treatment regimen in this study included 200 or 400 mg taken once, and 200 mg taken once daily for 2 or 3 days.

Terbinafine hydrochloride oral granules versus oral griseofulvin suspension in children with tinea capitis: results of two randomized, investigator-blinded, multicenter, international, controlled trials.

BACKGROUND: Although griseofulvin is currently considered the primary antifungal agent used to treat tinea capitis in many countries, increasingly higher doses and longer durations of treatment are becoming necessary to achieve effective treatment. Alternative antifungal therapies with shorter/simpler treatment regimens may be important to develop for this indication. OBJECTIVE: To compare the efficacy and safety of a new pediatric formulation of terbinafine hydrochloride oral granules with griseofulvin oral suspension in the treatment of tinea capitis. METHOD: Children (4-12 years of age) with clinically diagnosed and potassium hydroxide microscopy-confirmed tinea capitis were randomized in two identical studies (trial 1, trial 2) to once-daily treatment with terbinafine (5-8 mg/kg; n = 1040) or griseofulvin administered per label (10-20 mg/kg; n = 509) for a period of 6 weeks followed by 4 weeks of follow-up. End-of-study complete cure (negative fungal culture and microscopy with Total Signs and Symptoms Score [TSSS] = 0), and mycologic (negative culture and microscopy) and clinical cure (TSSS = 0) were primary and secondary efficacy variables, respectively. Efficacy analysis was based on pooled data using modified intent-to-treat population (those who received at least one dose of study drug and had positive baseline fungal culture, N = 1286). Safety assessments included monitoring of the frequency and severity of adverse events (AEs). RESULTS: Rates of complete cure and mycologic cure were significantly higher for terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P < .05). A majority (86.7%) of patients received griseofulvin, 10 to 19.9 mg/kg per day; complete cure rate was not found to be higher among patients who received griseofulvin more than 20 mg/kg per day compared with those who received less than 20 mg/kg per day. Complete cure rate was statistically significantly greater for terbinafine compared to griseofulvin in trial 1 (46.23% vs 34.01%) but not in trial 2 (43.99% vs 43.46%). On the basis of pooled data, clinical cure was higher for terbinafine than for griseofulvin, but the difference was not found to be statistically significant (P = .10). Subgroup analyses revealed that terbinafine was significantly better than griseofulvin for all cure rates--mycologic, clinical, and complete--among patients with Trichophyton tonsurans but not Microsporum canis (P < .001). For M. canis, mycologic and clinical cure rates were significantly better with griseofulvin than with terbinafine (P < .05). Approximately 50% of patients in each group reported an AE; almost all were mild or moderate in severity. Nasopharyngitis, headache, and pyrexia were most common in both groups. There were no drug-related serious AEs, no deaths, and no significant effects on weight or laboratory parameters, including liver transaminases. LIMITATIONS: In retrospect, a difference in the distribution of infecting microorganisms between the two trials was a limitation. Stringent adherence to griseofulvin doses recommended by prescribing information but smaller than those used in current clinical practice, and exclusion of adjuvant therapies such as shampoos or topical agents, which are routinely used in practice, are other limitations. CONCLUSIONS: Data from this largest pediatric trial of terbinafine to date indicate that terbinafine is efficacious and well tolerated in the treatment of tinea capitis. Terbinafine is an effective alternative to griseofulvin against T. tonsurans tinea capitis.

Topical retapamulin ointment, 1%, versus sodium fusidate ointment, 2%, for impetigo: a randomized, observer-blinded, noninferiority study.

BACKGROUND: Retapamulin is a novel pleuromutilin antibacterial developed for topical use. OBJECTIVE: To compare the efficacy and safety of retapamulin ointment, 1% (twice daily for 5 days), with sodium fusidate ointment, 2% (3 times daily for 7 days), in impetigo. METHODS: A randomized (2:1 retapamulin to sodium fusidate), observer-blinded, noninferiority, phase III study in 519 adult and pediatric (aged > or = 9 months) subjects. RESULTS: Retapamulin and sodium fusidate had comparable clinical efficacies (per-protocol population: 99.1 and 94.0%, respectively; difference: 5.1%, 95% confidence interval: 1.1-9.0%, p = 0.003; intent-to-treat population: 94.8 and 90.1%, respectively; difference: 4.7%, 95% confidence interval: -0.4 to 9.7%, p = 0.062). Bacteriological efficacies were similar. Success rates in the small numbers of sodium-fusidate-, methicillin- and mupirocin-resistant Staphylococcus aureus were good for retapamulin (9/9, 8/8 and 6/6, respectively). Both drugs were well tolerated. CONCLUSION: Retapamulin is a highly effective and convenient new treatment option for impetigo, with efficacy against isolates resistant to existing therapies.

Adverse cutaneous drug eruptions and HIV: a clinician's global perspective.

Adverse drug reactions (ADRs) are common and mostly avoidable. Some ADRs cannot as yet be predicted, but at-risk populations/patients and high-risk drugs are identifiable. HIV-infected patients are at risk of developing cutaneous ADRs, especially Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug hypersensitivity syndrome. Multiple factors of causation variably present in patients with HIV infection best explain the pathogenesis of these cutaneous ADRs. When no effective alternate therapy is available, drug rechallenge in HIV-infected patients can be attempted with little morbidity or mortality if done according to rationalized protocols.

Therapeutic Trial of Rifabutin After Rifampicin-Associated DRESS Syndrome in Tuberculosis-Human Immunodeficiency Virus Coinfected Patients.

Elimination of a rifamycin from the treatment regimen for tuberculosis negatively impacts outcomes. Cross-reactivity between the rifamycins after drug eruptions is unclear. We report 6 consecutive human immunodeficiency virus-infected patients with rifampicin-associated drug rash with eosinophilia and systemic symptoms (DRESS) syndrome confirmed on diagnostic rechallenge. The patients subsequently tolerated rifabutin. These data inform clinical management of tuberculosis-associated drug reactions.

Stevens Johnson Syndrome and Toxic Epidermal Necrolysis: Maternal and Foetal Outcomes in Twenty-Two Consecutive Pregnant HIV Infected Women.

INTRODUCTION: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) form a spectrum of a rare and life-threatening cutaneous drug reaction. SJS/TEN in pregnancy poses largely unknown risk factors and outcomes for both the mother and foetus compared to the general population. METHODS: We conducted a study of consecutive pregnant women admitted to single tertiary referral centre in South Africa with SJS/TEN over a 3 year period. They were all managed by the same medical team using the same protocols. We evaluated their underlying illnesses, offending drugs and the course of pregnancy and outcomes to determine factors influencing maternal and foetal outcomes. RESULTS: We identified twenty-two women who developed SJS/TEN while pregnant, all of them HIV-infected. Their median age was 29 years. The majority 16/22 (73%) had SJS, the milder variant of the disease affecting < 10% body surface area. Nevirapine was the offending drug in 21/22 (95%) cases. All 22 of the mothers survived with 3/22 (14%) developing postpartum sepsis. Pregnancy outcomes were known in 18/22 women and 9/18 (50%) babies were delivered by caesarean section. There were 2 foetal deaths at 21 and 31 weeks respectively and both were associated with post-partum sepsis. Postnatal complications occurred in 5 cases, 3 involving the respiratory system and the other two being low birth weight deliveries. Eight placentae and one foetus were sent for histology and none showed macroscopic or microscopic features of SJS/TEN. On follow-up, only 12/20 children were tested for HIV at 6 weeks post-delivery and none of them were HIV-infected. All had received prophylactic ARVs including nevirapine. CONCLUSIONS: TEN, the severe form of the disease, was associated with poorer foetal outcomes. SJS/TEN-associated mortality is not increased in HIV-infected pregnant women. Maternal SJS/TEN does not seem to commonly manifest in the foetus.

Safety and efficacy of pimecrolimus in atopic dermatitis: a 5-year randomized trial.

BACKGROUND AND OBJECTIVES: Atopic dermatitis (AD) primarily affects infants and young children. Although topical corticosteroids (TCSs) are often prescribed, noncorticosteroid treatments are needed because compliance with TCSs is poor due to concerns about their side effects. In this longest and largest intervention study ever conducted in infants with mild-to-moderate AD, pimecrolimus 1% cream (PIM) was compared with TCSs. METHODS: A total of 2418 infants were enrolled in this 5-year open-label study. Infants were randomized to PIM (n = 1205; with short-term TCSs for disease flares) or TCSs (n = 1213). The primary objective was to compare safety; the secondary objective was to document PIM's long-term efficacy. Treatment success was defined as an Investigator's Global Assessment score of 0 (clear) or 1 (almost clear). RESULTS: Both PIM and TCSs had a rapid onset of action with >50% of patients achieving treatment success by week 3. After 5 years, >85% and 95% of patients in each group achieved overall and facial treatment success, respectively. The PIM group required substantially fewer steroid days than the TCS group (7 vs 178). The profile and frequency of adverse events was similar in the 2 groups; in both groups, there was no evidence for impairment of humoral or cellular immunity. CONCLUSIONS: Long-term management of mild-to-moderate AD in infants with PIM or TCSs was safe without any effect on the immune system. PIM was steroid-sparing. The data suggest PIM had similar efficacy to TCS and support the use of PIM as a first-line treatment of mild-to-moderate AD in infants and children.

Dermatological manifestations of measles infection in hospitalised paediatric patients observed in the 2009 - 2011 Western Cape epidemic.

Introduction. Measles is an acute vaccine-preventable infection common in childhood. In this study, the common dermatological signs of measles were designated the 'classic dermatological measles syndrome'. Methods. We attempted to ascertain the prevalence of 'non-classic' dermatological measles presentation in 69 paediatric patients admitted to New Somerset Hospital, Western Cape, during the recent South African measles outbreak. The patients were examined and photographed, after informed consent had been obtained, and findings were assessed by 1 dermatology consultant and 6 dermatology registrars. Measles infection was confirmed in 38 of the patients by means of IgM testing. The data were analysed using Stata version 11.1 statistical software. Outcomes. Of the group, 17.4% (95% CI 8.2 - 26.6%) displayed a classic measles dermatological picture, although all had been clinically diagnosed and admitted as complicated measles cases. Those serologically confirmed to have measles (N=38), 26.3% (95% CI 11.6 - 40.9%) conformed to the classic dermatological picture. Therefore, a significant majority of these patients presented with what was considered in this study to be a 'non-classic' dermatological picture. Conclusions. Measles infection in a paediatric population requiring admission may frequently present without a full-house classic dermatological picture. Recognised signs in isolation may be of greater value than the classically described syndrome as a whole. 'Non-classic' dermatological forms may occur more frequently than anticipated in complicated cases needing admission. Skin necrosis may be associated with measles.

"I Found it on the Internet": Preparing for the e-patient in Oman.

In the Information Age, the communication patterns between doctor and patient are changing. Using Everett Rogers' theory of Diffusion of Innovations, this paper begins by examining the diffusion of the Internet in the world and in Oman. It then considers the emergence of e-patients. The characteristics of e-patients are described in some detail. The paper ends by describing steps that should be taken when teaching medical students in Oman so that they can be prepared for e-patients.