Gail Todd

Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury

Background and Aims: Hepatotoxicity, especially liver fibrosis, is the major concern with long‐term, ‘low‐dose’ oral methotrexate (MTX) therapy for psoriasis. The histological features are non‐specific and resemble those of non‐alcoholic steatohepatitis (NASH). Moreover, most of the risk factors of MTX‐induced liver injury are also associated with NASH. In this study, we investigate whether NASH contributes to the prevalence and progression of MTX‐induced liver injury in patients receiving MTX for psoriasis.

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 ≧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.

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.

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.

Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons.

The incidence of cutaneous adverse drug reactions (CADRs) to first‐line antituberculosis drugs (FLTDs) is higher in HIV–tuberculosis coinfection. However, the utility of patch testing to identify the offending drug in this patient subgroup has been poorly studied.

Acute Scleritis in Porphyria Cutanea Tarda

We examined three patients who had dermatologic and biochemical manifestations of porphyria cutanea tarda and localized thinning or excavation in the sun-exposed interpalpebral sclera, adjacent to the cornea. All three patients had signs of acute scleritis. The acute scleritis responded to oral indomethacin in one patient, but systemic corticosteroids were required to control the inflammation in the other two patients. Phlebotomy, protection from sunlight, and refraining from alcohol played an important part in the treatment of the patients.

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.

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 Kaposis 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. J. Med. Virol. 88:292–303, 2016.