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

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.

Background Post-kala-azar dermal leishmaniasis (PKDL) manifests as a skin eruption after healing of visceral leishmaniasis (VL), either spontaneously or as a result of treatment. This study was undertaken to describe the demographic, clinical, and histopathologic features of PKDL in Nepal.



Methods  Demographic, clinical, microbiologic, and histopathologic features and response to treatment were studied in 22 patients with PKDL from April 1998 to March 2000.



Results  PKDL accounted for 0.13% of all new dermatologic cases. There were 13 (59.1%) males and nine (40.9%) females. A past history of kala-azar was present in all but one patient. A family history of kala-azar was noted in eight (36.4%) patients. All patients presented with multiple types of lesion, except for two in whom only macular lesions were seen. Oral lesions in the form of nodules and plaques were seen in four patients. Generalized lymphadenopathy was present in five patients. Slit skin smears revealed Leishman–Donovan bodies (LDBs) in nine (40.9%) patients. In macular lesions, there was a sparse infiltrate of plasma cells, lymphocytes, or histiocytes in the upper dermis. There was a dense chronic inflammatory infiltrate comprising plasma cells, lymphocytes, histiocytes, and epithelioid cells in the entire dermis from papules, plaques, or nodules. Giemsa staining of biopsy specimens revealed LDBs in seven (38.9%) patients only. Fine needle aspiration from epitrochlear lymph nodes in two patients demonstrated LDBs. All patients responded well to treatment with minimal side-effects.



Conclusions  This study emphasizes the need to be aware of the possibility of cases of PKDL in endemic regions of leprosy, as the conditions may be difficult to distinguish clinically and histopathologically.

Post-kala-azar dermal leishmaniasis in Nepal.

Onychomycosis, a fungal infection of the nail is responsible for up to 50.0% of all nail diseases. Though, dermatophytes are most frequently implicated as the causative agents in onychomycosis, yeast and molds are increasingly recognized as causative pathogens. This study was aimed to know the clinical and mycological pattern of onychomycosis in eastern Nepal. Eighty-two clinically diagnosed patients of onychomycosis attending the Dermatology Outpatient department of a tertiary hospital over a period of one year were enrolled in this study. Clipping from the severely affected nail and skin scrapping from active border of the skin lesions if associated were collected from each patient and subjected to microscopy and culture for identification of fungi. The commonest affected age group was 21-40 years. The male: female ratio was 2.7:1. Fifty-one patients had isolated fingernail involvement, while involvement of toenails was seen in 15 patients. Distolateral subungual onychomycosis (67%) was the commonest clinical type followed in decreasing order by superficial white onychomycosis (14.6%), proximal subungual onychomycosis (9.8%), candidal onychomycosis (7.4%) and total dystrophic onychomycosis (1.2%). Trichophyton mentagrophytes (28.8%) was the most common pathogen isolated followed by Trichophyton rubrum (21.2%), Trichophyton tonsurans (11.5%), Candida albicans (11.5%), Trichospron beigelii, (9.6%), Epidermophyton floccosum (7.7%), Trichophyton violaceum (5.8%), and Aspergillus flavus (3.9%). Distolateral subungual onychomycosis was the most common clinical presentation and T. mentagrophytes and T. rubruni were the most frequently isolated fungi for onychomycosis in eastern Nepal.

/pdf/onychomycosis-in-eastern-nepal-273wm37l24.pdf

Arun Agarwalla

Papers

Dapsone Hypersensitivity Syndrome: A Clinico‐Epidemiological Review

Tinea capitis in eastern Nepal.

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

Post-kala-azar dermal leishmaniasis in Nepal.

Onychomycosis in eastern Nepal.