Adverse drug reactions (ADRs) result in major health problems in the United States in both the inpatient and outpatient setting. ADRs are broadly categorized into predictable (type A and unpredictable (type B) reactions. Predictable reactions are usually dose dependent, are related to the known pharmacologic actions of the drug, and occur in otherwise healthy individuals, They are estimated to comprise approximately 80% of all ADRs. Unpredictable are generally dose independent, are unrelated to the pharmacologic actions of the drug, and occur only in susceptible individuals. Unpredictable reactions are subdivided into drug intolerance, drug idiosyncrasy, drug allergy, and pseudoallergic reactions. Both type A and B reactions may be influenced by genetic predisposition of the patient

Drug allergy: an updated practice parameter.

BackgroundCases of severe drug hypersensitivity, demonstrating a variable spectrum of cutaneous and systemic involvement, are reported under various names, especially drug reaction with eosinophilia and systemic symptoms (DRESS). Case definition and overlap with other severe cutaneous adverse reactions (SCAR) are debated. ObjectivesTo analyse the spectrum of signs and symptoms of DRESS and distribution of causative drugs in a large multicentre series. Patients and methodsRegiSCAR, a multinational registry of SCAR, prospectively enrolled 201 potential cases from 2003 to mid-2009. Using a standardized scoring system, 117 cases were validated as showing probable or definite DRESS. ResultsThe male/female ratio was 080; females were borderline significantly younger than males. Next to the ubiquitous exanthema, the main features were eosinophilia (95%), visceral involvement (91%), high fever (90%), atypical lymphocytes (67%), mild mucosal involvement (56%) and lymphadenopathy (54%). The reaction was protracted in all but two patients; two patients died during the acute phase. Drug causality was plausible in 88% of cases. Antiepileptic drugs were involved in 35%, allopurinol in 18%, antimicrobial sulfonamides and dapsone in 12% and other antibiotics in 11%. The median time interval after drug intake was 22days (interquartile range 17-31) for all drugs with (very) probable causality, with differences between drugs. ConclusionThis prospective observational study supports the hypothesis that DRESS is an original phenotype among SCAR in terms of clinical and biological characteristics, causative drugs, and time relation. The diversity of causative drugs was rather limited, and mortality was lower than that suggested by prior publications.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/bjd.12501

Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study

Post-kala-azar dermal leishmaniasis (PKDL) is a complication of visceral leishmaniasis (VL); it is characterised by a macular, maculopapular, and nodular rash in a patient who has recovered from VL and who is otherwise well. The rash usually starts around the mouth from where it spreads to other parts of the body depending on severity. It is mainly seen in Sudan and India where it follows treated VL in 50% and 5-10% of cases, respectively. Thus, it is largely restricted to areas where Leishmania donovani is the causative parasite. The interval at which PKDL follows VL is 0-6 months in Sudan and 2-3 years in India. PKDL probably has an important role in interepidemic periods of VL, acting as a reservoir for parasites. There is increasing evidence that the pathogenesis is largely immunologically mediated; high concentrations of interleukin 10 in the peripheral blood of VL patients predict the development of PKDL. During VL, interferon gamma is not produced by peripheral blood mononuclear cells (PBMC). After treatment of VL, PBMC start producing interferon gamma, which coincides with the appearance of PKDL lesions due to interferon-gamma-producing cells causing skin inflammation as a reaction to persisting parasites in the skin. Diagnosis is mainly clinical, but parasites can be seen by microscopy in smears with limited sensitivity. PCR and monoclonal antibodies may detect parasites in more than 80% of cases. Serological tests and the leishmanin skin test are of limited value. Treatment is always needed in Indian PKDL; in Sudan most cases will self cure but severe and chronic cases are treated. Sodium stibogluconate is given at 20 mg/kg for 2 months in Sudan and for 4 months in India. Liposomal amphotericine B seems effective; newer compounds such as miltefosine that can be administered orally or topically are of major potential interest. Although research has brought many new insights in pathogenesis and management of PKDL, several issues in particular in relation to control remain unsolved and deserve urgent attention.

Post-kala-azar Dermal Leishmaniasis

Despite recent advances in understanding the immunopathogenesis of oral lichen planus (LP), the initial triggers of lesion formation and the essential pathogenic pathways are unknown. It is therefore not surprising that the clinical management of oral LP poses considerable difficulties to the dermatologist and the oral physician. A consensus meeting was held in France in March 2003 to discuss the most controversial aspects of oral LP. Part 1 of the meeting report focuses on (1) the relationship between oral LP and viral infection with special emphasis on hepatitis C virus (HCV), and (2) oral LP pathogenesis, in particular the immune mechanisms resulting in lymphocyte infiltration and keratinocyte apoptosis. Part 2 focuses on patient management and therapeutic approaches and includes discussion on malignant transformation of oral LP.

https://exodontia.info/files/Current_controversies_in_oral_lichen_planus_Part_1.pdf

Current controversies in oral lichen planus: report of an international consensus meeting. Part 1. Viral infections and etiopathogenesis.

https://www.cidjournal.com/article/S0738-081X(09)00247-8/pdf

Epidemiology of superficial fungal infections.

Diaminodiphenyl sulphone (dapsone) is a drug of choice in the treatment of leprosy. It is also useful for the treatment of many neutrophilic and other dermatoses. Dapsone hypersensitivity syndrome is a rare but well recognized serious adverse effect characterized by fever, skin rashes, generalized lymphadenopathy, hepatitis, and hepato-splenomegaly. Twenty-six patients with dapsone hypersensitivity syndrome were studied for clinical profile, outcome, and prognosis. The male:female ratio was 2.2:1, and the mean age was 33.19 years (range 13 to 64 years). The interval between start of dapsone therapy and appearance of symptoms varied from 2-7 weeks (mean 29.82 days). Twenty-four patients received dapsone as a part of multi-drug therapy for leprosy; the other two patients received dapsone for lichen planus and acne vulgaris. Exfoliative dermatitis was the most common cutaneous manifestation followed by erythematous maculo-papular eruption and Stevens-Johnson syndrome-like lesion. The other common systemic manifestations were: fever (26 cases), itching (22 cases), lymphadenopathy (21 cases), jaundice (21 cases), pallor (20 cases), hepatomegaly (19 cases), and pedal edema (14 cases). Investigation profile revealed elevated levels of serum liver enzymes in 100% of patients, elevated erythrocyte sedimentation rate in 92.3%, raised billirubin in 84.6%, leucocytosis in 69.23%, low hemoglobin (<9 gm/dl) in 46.15% and hypoproteinemia in 42.3%. Eosinophilia, hemolytic anemia, and reticulocytosis count were found in 4 patients each. All the patinents had favorable outcomes except three who died due to hepatic failure. Medical personnel must be aware of this potentially fatal syndrome, because it can cause considerable morbidity and mortality.

Dapsone Hypersensitivity Syndrome: A Clinico‐Epidemiological Review

Vitiligo is an acquired depigmenting disorder having disfiguring consequences. Many treatments have been attempted with varying reports of success. A parallel-group, assessor blinded, randomized, controlled trial was designed to compare the efficacy and adverse effects of narrowband UVB (NBUVB) with oral psoralen UVA (PUVA) therapy in the treatment of vitiligo. Patients aged 13-70 years with vitiliginous lesions involving more than 5% body surface area were eligible for the study. In total, 56 patients were randomized in a 1:1 ratio to oral PUVA or NBUVB phototherapy groups. Patients were assessed for the percentage of repigmentation over the depigmented areas as the primary outcome measure at each visit during the first three months and then monthly within the next three months. The incidence of adverse effects was also noted during the study period as the secondary outcome measure. The median repigmentation achieved at the end of the six-month therapy course was 45% in the NBUVB group and 40% in the oral PUVA group. Focal vitiligo had the best response in both treatment groups. There were lesser adverse effects within the NBUVB (7.4%) than in the PUVA (57.2%) group. Two PUVA patients discontinued therapy due to severe dizziness. There was no significant difference in the mean degree of repigmentation; however, NBUVB carried a greater response rate and might be superior to oral PUVA with better tolerance and color match with the surrounding normal skin, as well as fewer side effects in the treatment of vitiligo.

Systemic PUVA vs. narrowband UVB in the treatment of vitiligo: a randomized controlled study

Background Tinea capitis is an increasing public health concern throughout the world. The clinical types and etiological agents vary from time to time and place to place. This study was undertaken to identify the etiological agents and to determine the clinico-etiological correlation of tinea capitis in eastern Nepal.



Methods  Sixty-nine clinically diagnosed cases of tinea capitis were enrolled in this study. Hair roots and skin scrapings were collected from each patient and subjected to microscopy and culture for identification of fungal hyphae and spores.



Results  Tinea capitis accounted for 4.6% of all dermatophyte infections: 68.1% occurred in patients below the age of 11 years with a male to female ratio of 1 : 1.9. “Gray patch” was the most common clinical type (52.2%), followed by “black dot” (17.4%), seborrhoeic dermatitis (13%), alopecia areata (11.6%) and pustular (4.3%). Direct microscopy of hair was positive in 62.3% of patients. Culture positivity was found in 56.7% of patients. Common isolated organisms were Trichophyton violaceum (48.71%), T. mentagrophytes (15.38%), T. tonsurans (12.82%), Microsporum canis (7.69%), T. rubrum and M. gypseum (5.12% each), and M. audouinii and M. nanum (2.56% each).



Conclusions Trichophyton violaceum was the most common pathogen of tinea capitis. The clinical manifestations were variable and “gray patch” was the most common clinical presentation in this part of the world.

Tinea capitis in eastern Nepal.

A total number of 86 cases of Lichen planus (LP) were seen over a period of one and a half years. This constituted 0.58% of 14833 new dermatological patients seen. Hepatitis B and C viral (HBV & HCV) serology was carried out in 64 patients and 43 age and sex matched controls. In the examined patients, 35 (54.27%) had the skin lesions only. Oral lesions were present in 15 (23.4%) of the patients in addition to skin lesions, while 14 (21.9%) had only oral involvement. Serology for HBsAg and HCV was negative in all types of LP patients and the controls. In Nepal, HBV and HCV seem to be not important in the pathogenesis of LP.

A study from Nepal showing no correlation between lichen planus and hepatitis B and C viruses.

Chronic renal failure, regardless of its cause, often produces specific dermatological abnormalities, which can develop long before failure manifests clinically. Our aim was to study the clinical pattern of skin and nail changes in chronic renal failure and also study the associations of these changes with age, sex, etiology and duration of the chronic renal failure. A total of 104 diagnosed cases of chronic renal failure were included in the study over a period of 1 year. Equal numbers of age- and sex-matched individuals were taken as controls. The male : female ratio was 1.4:1. The mean duration of chronic renal failure was 19 +/- 20 months. Among cases and controls, 72% and 16% had skin changes, respectively. Xerosis was the most common of the skin changes (28%), followed by hyperpigmentation (20%), pruritus (15%), infectious diseases (5%) and other skin changes (33%) in chronic renal failure patients. Abnormal nail changes were seen in 82% of the cases compared to only 8% of the controls. In the cases, white nail was most common followed by brown and half-and-half nail. Pruritus was significantly higher in the dialysis group whereas the nail changes were significantly higher in the non-dialysis group. The skin and nail changes were common in chronic renal failure and manifested in various forms. Thus, thorough inspection of the integument might reveal markers of occult renal disease.

Sudha Agrawal

Papers

Dapsone Hypersensitivity Syndrome: A Clinico‐Epidemiological Review

Systemic PUVA vs. narrowband UVB in the treatment of vitiligo: a randomized controlled study

Tinea capitis in eastern Nepal.

A study from Nepal showing no correlation between lichen planus and hepatitis B and C viruses.

Pattern of skin and nail changes in chronic renal failure in Nepal : A hospital-based study