Predictors of disease severity in drug reaction with eosinophilia and systemic symptoms

Background: Drug reaction with eosinophilia and systemic symptoms is an outcome of a complex interaction between specific drugs, certain herpesviruse types and the immune system of the affected individual and is characterized by an unpredictable course and recurrent flares even after withdrawal of the offending drug and administration of systemic steroids. Aims: To identify the predictors of disease severity in drug reaction with eosinophilia and systemic symptoms. Methods: After obtaining ethical clearance from the institutional ethics committee and a written informed consent from individual study participant, the first hundred patients who required inpatient care in Government Medical College, Kozhikode with drug reaction with eosinophilia and systemic symptoms from January 1st 2011 were included in this study aimed to identify the predictors of disease severity in drug reaction with eosinophilia and systemic symptoms. Results: Male-to-female ratio of the study group was 0.8:1. The presence of atypical cells in peripheral smear and advanced age were found to be predictors of disease severity in drug reaction with eosinophilia and systemic symptoms, whereas, sex, facial erythema and edema and absolute eosinophil count were found not to be predictors of the same. Limitations: The main limitation of this study was our inability to assess the role of human leukocyte antigen (HLA) association and herpes virus reactivation in disease severity in drug reaction with eosinophilia and systemic symptoms. This study was also not designed to evaluate the response to treatment given and the mortality caused by drug reaction with eosinophilia and systemic symptoms. Conclusions: Studies on the predictors of severity in drug reaction with eosinophilia and systemic symptoms in different population groups may enable us to identify the warning signs and help to formulate the standard therapeutic guidelines.

Pyoderma gangrenosum: A clinico-epidemiological study.

Background: Pyoderma gangrenosum is a neutrophilic dermatosis of unknown etiology, with inconstant systemic associations and a variable prognosis. Aims: To study the clinical features and systemic associations of pyoderma gangrenosum and its response to treatment. Methods: All patients diagnosed to have pyoderma gangrenosum at the dermatology department of the Government Medical College, Kozhikode, from January 01, 2005 to December 31, 2014 were included in this prospective study. Results: During the 10-year study period, 61 patients were diagnosed to have pyoderma gangrenosum. A male predilection was noted. The most common clinical type was ulcerative pyoderma gangrenosum (90.2%). More than 60% of patients had lesions confi ned to the legs; 78.7% had a single lesion and 27.9% had systemic associations. Most patients required systemic steroids. Patients with disease resistant to steroid therapy were treated with intravenous immunoglobulin G and split-thickness skin grafts under immunosuppression induced by dexamethasone pulse therapy. All except one patient attained complete disease resolution. Limitations: The main limitation of our study was the small sample size. Conclusions: The male predilection documented by us was contrary to most previous studies. We found split-thickness skin graft to be a useful option in resistant cases. More prospective studies may enable the formulation of better diagnostic criteria for pyoderma gangrenosum and improve its management.

Drug reaction with eosinophilia and systemic symptoms (DRESS): A histopathology based analysis.

Background: The data on the histology of cutaneous lesions of drug reaction with eosinophilia and systemic symptoms (DRESS) is limited. Aims: To study the histopathology of cutaneous lesions of drug reaction with eosinophilia and systemic symptoms (DRESS) and to identify any features with diagnostic or prognostic signifi cance. Methods: All patients admitted to the dermatology ward of government medical college, Kozhikode from January 1, 2014 to December 31, 2014 with probable or defi nite DRESS as per the RegiSCAR scoring system and who were willing to undergo skin biopsy were included in this prospective study. Results: The study population comprised of nine patients. The consistent histological fi nding documented was the predominantly lymphocytic dermal infl ammatory infi ltrate. Four of the fi ve patients whose histology revealed focal interface dermatitis and keratinocyte vacuolation with or without apoptotic keratinocytes, had elevated liver transaminases. Tissue eosinophilia was associated with disease fl ares. The presence of atypical lymphocytes in peripheral smear and histological evidence of dense dermal infl ammatory infi ltrate showed an association with hepatic involvement. Limitations: The main limitations of our study were the small sample size and our inability to carry out a detailed immunohistochemistry work-up. Conclusions: In the appropriate setting, varying combinations of epidermal hyperplasia, spongiosis, parakeratosis and individually necrotic keratinocytes in the background of lymphocyte predominant dermal infi ltrate (with some atypia) favor a diagnosis of drug reaction with eosinophilia and systemic symptoms. Female sex, the presence of atypical lymphocytes in peripheral smear, dense dermal infl ammatory infi ltrate, tissue eosinophilia and interface dermatitis with or without keratinocyte necrosis was associated with a poor prognosis.

Drug reaction with eosinophilia and systemic symptoms: Observations from a tertiary care institution.

Background: Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe drug reaction which can mimic a viral infection, an autoimmune disease or a neoplastic disease. Aims: To study the clinical and epidemiological aspects of DRESS and to identify the precipitating drugs. Methods: All patients admitted to the dermatology ward of our tertiary care hospital from 1 st October 2010 to 30 th September 2013 with probable or definite DRESS as per the RegiSCAR scoring system were included in this prospective study. The clinical manifestations observed in the study population were studied and the common offending drugs were identified. Results: During the 3 year study period, 26 patients fulfilled criteria for probable or definite DRESS. In more than 50% of cases, the culprit drug was phenytoin. Most common symptoms observed were fever, rash and facial edema. Liver was the most common internal organ affected. Most of the patients responded to withdrawal of the drug and administration of steroids for 3-6 weeks. One patient with dapsone-induced DRESS died. Conclusions: Intense facial erythema and edema and an elevated eosinophil count were not found to be bad prognostic factors. In most instances the flare ups during the course of the disease could be managed with a slower tapering of steroids. More prospective studies on DRESS are required to assess the prognostic factors and to formulate better diagnostic criteria.

Drug-induced hypersensitivity syndrome with human herpesvirus-6 reactivation.

A 45-year-old man, on carbamazepine for the past 3 months, was referred as a case of atypical measles. On examination, he had high-grade fever, generalized itchy rash, cough, vomiting and jaundice. A provisional diagnosis of drug hypersensitivity syndrome to carbamazepine was made with a differential diagnosis of viral exanthema with systemic complications. Laboratory investigations revealed leukocytosis with eosnophilia and elevated liver enzymes. Real-time multiplex polymerase chain reaction (PCR) on throat swab and blood was suggestive of human herpesvirus-6 (HHV-6). Measles was ruled out by PCR and serology. The diagnosis of drug-induced hypersensitivity syndrome (DIHS) was confirmed, which could explain all the features manifested by the patient. HHV-6 infects almost all humans by age 2 years. It infects and replicates in CD4 T lymphocytes and establishes latency in human peripheral blood monocytes or macrophages and early bone marrow progenitors. In DIHS, allergic reaction to the causative drug stimulates T cells, which leads to reactivation of the herpesvirus genome. DIHS is treated by withdrawal of the culprit drug and administration of systemic steroids. Our patient responded well to steroids and HHV-6 was negative on repeat real-time multiplex PCR at the end of treatment.

Spa therapy in dermatology.

Spa therapy constitutes the use of mineral springs and thermal mud to soothe and heal various ailments. Like the mineral springs, seas and oceans are also important centers for spa therapy of which the most important is Dead Sea (DS). DS has been famous for thousands of years for its miraculous curative and cosmetic properties. Intensive research is going on using DS minerals in a wide range of dermatological conditions especially psoriasis, atopic dermatitis, vitiligo and other eczemas and several papers have been published in various international and pharmacological journals.

Cutaneous manifestations of chikungunya during a recent epidemic in Calicut, north Kerala, south India.

Background: There was a recent epidemic of chikungunya (CKG) in Calicut and other northern districts of Kerala, South India, affecting thousands of people. Aims: To study the cutaneous manifestations of CKG and to have a serological and histopathological correlation. Methods: A total of 162 patients (63 males and 99 females) with cutaneous manifestations of CKG were enrolled in the study and serological confirmation was done with capture IgM ELISA for CKG. Skin biopsy was done in all representative cases. Results: Cutaneous manifestations were found more in females. There were 23 children, the youngest being 39 days old. Generalized erythematous macular rash was the most common finding. Vesicles and bullae were also common especially in infants. Localized erythema of the nose and pinnae, erythema and swelling of the pre existing scars and striae and toxic epidermal necrolysis-like lesions sparing mucosae were the other interesting findings. Different types of pigmentation were observed with a striking nose pigmentation in a large number of patients, by looking at which even a retrospective diagnosis of CKG could be made. Hence we suggest this peculiar pigmentation may be called "chik sign". There was flare up of existing dermatoses like psoriasis, lichen planus and unmasking of Hansen's disease with type 1 reaction. Serological tests were positive in 97%. Some hitherto unreported histopathologic findings like melanophages in the erythematous rashes were observed. Conclusion: A spectrum of cutaneous manifestations of CKG with a wide variety of unusual presentations with confirmed serological and histopathological evidence was encountered.