Charoen Choonhakarn

Strong association between hla-b * 5801 and allopurinol-induced Stevens–johnson syndrome and toxic epidermal necrolysis in a Thai population

Objectives Allopurinol, a uric acid lowering drug commonly used for hyperuricemia and gouty arthritis, has been reported as a common cause of severe cutaneous adverse drug reactions (SCAR) including Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). A strong association between allopurinol-induced SCAR and HLA-B*5801 was observed in a Han Chinese population with high frequency of this allele, whereas only a moderate association was observed in populations with low frequency (i.e. European and Japanese). This study investigated the relationship between SJS/TEN and HLA-B*5801 in a Thai population that has a high allelic frequency of this allele. Methods Twenty-seven allopurinol-induced SJS/TEN and 54 allopurinol-tolerant patients were enrolled in the study. The presence of HLA-B*5801 and HLA-B genotypes in these patients were analyzed using a PG5801 DNA detection kit and sequence-based typing, respectively. Results All of the 27 (100%) allopurinol-induced SJS/TEN patients who were examined carried HLA-B*5801 whereas only seven (12.96%) of the control patients had this allele. The risk of allopurinol-induced SJS/TEN was significantly greater in patients with HLA-B*5801 when compared with those who did not carry this allele, with an odds ratio of 348.3 (95% confidence interval=19.2–6336.9, P = 1.6×10−13). The sensitivity and specificity of the HLA-B*5801 allele for prediction of allopurinol-induced SJS/TEN were 100 and 87%, respectively. By assuming a 0.2% prevalence rate, the positive predictive value and the negative predictive value of the HLA-B*5801 allele was 1.52 and 100%, respectively. Conclusion A strong association of allopurinol-induced SJS/TEN with the HLA-B*5801 allele was observed in a Thai population. The results suggest that HLA-B*5801 is a valid genetic marker for screening Thai individuals who may be at risk for allopurinol-induced life-threatening SJS and TEN.

Association between HLA-B*1502 and carbamazepine-induced severe cutaneous adverse drug reactions in a Thai population

Carbamazepine (CBZ) has been reported as the most common culprit drug for Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in several Asian countries including Thailand. A strong association between HLA‐B*1502 and CBZ‐induced SJS/TEN has been reported in Han Chinese but not in Caucasian and Japanese populations. A case–control study was conducted to determine whether HLA‐B*1502 is a valid pharmacogenetic test for SJS/TEN caused by CBZ in a Thai population. Among 42 CBZ‐induced patients with SJS/TEN, 37 (88.10%) patients carried the HLA‐B*1502 while only 5 (11.90%) of the CBZ‐tolerant controls had this allele. The risk of CBZ‐induced SJS/TEN was significantly higher in the patients with HLA‐B*1502, with an odds ratio (OR) of 54.76 [95% confidence interval (CI) 14.62–205.13, p = 2.89 × 10−12]. The sensitivity and specificity of HLA‐B*1502 for prediction of CBZ‐induced SJS/TEN were 88.10%. By assuming a 0.27% as a prevalence rate of CBZ‐induced SJS/TEN in a Thai population, the positive predictive value (PPV) and negative predictive value (NPV) of the HLA‐B*1502 were 1.92% and 99.96%. Results from this study suggest that HLA‐B*1502 may be a useful pharmacogenetic test for screening Thai individuals who may be at risk for CBZ‐induced SJS and TEN.

Disseminated Infection Due to Rapidly Growing Mycobacteria in Immunocompetent Hosts Presenting with Chronic Lymphadenopathy: A Previously Unrecognized Clinical Entity

Disseminated infection due to rapidly growing mycobacteria is uncommon and occurs mostly in immunocompromised patients. We report 16 cases of such infection with an unusual presentation seen at Srinagarind Hospital, a university hospital in northeastern Thailand. The clinical features were different from those in previous reports. All of the patients presented with chronic bilateral cervical lymphadenopathy. Twelve had mycobacterial involvement of other organs (sinuses, 6 patients; lungs, 4; liver, 4; spleen, 3; skin, 3; bone and joint, 2; and tonsils, 2). An interesting occurrence in 11 patients was 14 episodes of reactive skin manifestations (Sweets syndrome, 9; generalized pustulosis and erythema nodosum, 2 each; and pustular psoriasis, 1). No identifiable predisposing factors, including human immunodeficiency disease, were found in these patients. However, 8 patients had 11 episodes of prior infection or coinfection with other opportunistic pathogens (salmonellosis, 4; penicilliosis, 3; pulmonary tuberculosis, 2; and melioidosis and cryptococcosis, 1 each). These findings suggest that cell-mediated immunity is defective in these patients.

Lupus erythematosus tumidus

Background  Lupus erythematosus tumidus (LET) is a rare form of chronic cutaneous lupus erythematosus that characteristically presents as a succulent, erythematous plaques on sun‐exposed areas. The histopathological change that primarily distinguishes LET from other variants of cutaneous lupus erythematosus is the lack of alterations of the dermo–epidermal junction and epidermis. Our purpose was to describe 15 cases of LET from Thailand.

Haplotype associations of the major histocompatibility complex with psoriasis in Northeastern Thais

Background  To evaluate the distributions of the human leukocyte antigen (HLA) at class I and II loci that may contribute to the genetic susceptibility to psoriasis patients in the north‐eastern Thai population.

Familial Amyloidosis Cutis Dyschromica: Six Cases from Three Families

Amyloidosis cutis dyschromica, a rare form of primary cutaneous amyloidosis requiring histopathological confirmation, is characterized by generalized, asymptomatic hyperpigmentation intermingled with several hypopigmented spots without papulation, atrophy, and telangiectasia. Its onset usually begins before puberty. We describe six patients from three families, four male and two female. The mean age at onset was 10.2 years. Although the skin eruptions had developed extensively since childhood, systemic involvement was not evident even after long‐term follow‐up. Due to its unique and characteristic features, this condition should be considered as a separate entity and differentiated from other variants of primary cutaneous amyloidosis. The familial occurrence in our report suggests a genetic causal factor in this disease.

Cutaneous polyarteritis nodosa: a report of a case associated with melioidosis (Burkholderia pseudomallei)

A 22‐year‐old Thai woman was hospitalized with a 1‐month history of high‐grade fever and slowly progressing multiple erythematous painful nodules on both legs. A history of arthralgia in the knee and ankle joints was presented.

Azathioprine‐induced Sweet's syndrome and published work review

Hypersensitivity to azathioprine can manifest with a wide clinical spectrum. Azathioprine‐induced Sweets syndrome (SS) is rare and usually overlooked because it can mimic disease exacerbation and sepsis. This study aims to characterize the clinical findings of azathioprine‐induced SS. A retrospective analysis of the records of three patients diagnosed with azathioprine‐induced SS and a review of the relevant English‐language published work was performed. Twelve (71%) of the 17 patients were male, ranging 9–89 years in age (mean, 47.2). The time of onset after starting azathioprine was 5–28 days (mean, 13.3). The most common associated disease was inflammatory bowel disease including ulcerative colitis and Crohns disease (76%). The clinical features typically consisted of fever and classic rash of SS with pustules and vesicles. The lesions occurred most commonly on the face and trunk. Systemic involvement was rare and no hypotension or shock was reported as seen in azathioprine hypersensitivity syndrome. Thiopurine methyltransferase activity is not predictive of this type of adverse effect. Most patients dramatically responded to systemic corticosteroids. Azathioprine‐induced SS may be underdiagnosed because it can be easily misinterpreted as inflammatory bowel disease‐associated skin eruption. Patients with inflammatory bowel disease may be at higher risk of this condition. Early recognition and drug withdrawal can decrease morbidity of the patients.

Cutaneous Metaplastic Synovial Cyst

Metaplastic synovial cyst of the skin is a recently recognized entity characterized by an intradermal nodule that usually occurs at the site of previous surgical trauma. Histologically, the lesion demonstrates a cystic structure with villous‐like projections and a lining resembling hyperplastic synovium. We have studied two patients with rheumatoid arthritis, aged 46 and 55 years, who presented with cystic nodules localized on the thumb and great toes, respectively, without any history of previous trauma or surgical procedures performed in the areas. The presence of vimentin and CD 68 positivity of the cells lining the cyst walls supports the similarities between normal and metaplastic synovium. We hypothesize that constant pressure on the great toe, repeated manipulation of the finger, and chronic inflammation around the affected joints may have played roles in the pathogenesis of the lesions in our patients.

Lipodermatosclerosis: a clinicopathologic correlation

Lipodermatosclerosis (LDS) is a chronic fibrosing panniculitis associated with venous insufficiency. Although LDS is often a clinical diagnosis, it can be confused with other panniculitides. Microscopic examination is therefore essential to support the diagnosis in this condition. Histopathologic changes, however, have not been extensively defined. The purpose of this study was to characterize the histopathologic spectrum of this condition correlated with clinical manifestation.