Basal cell carcinoma in chronic arsenicism occurring in Queensland, Australia, after ingestion of an asthma medication.

BACKGROUND: Ingestion of trivalent inorganic arsenic has long been recognized as a cause of basal cell carcinomas (BCCs) and has been reported most often in Taiwan and Singapore. OBJECTIVE: Our purpose was to study the clinical and histologic characteristics of BCCs occurring in Australian Caucasians as a consequence of chronic arsenicism due to ingestion of an arsenic-containing medication. METHODS: Self-referred persons with a history of ingestion of Bell's Asthma Medication were interviewed, and skin examinations were performed. Local age- and sex-matched patients with BCCs were used to compare the distribution and histologic subtypes of BCCs in arsenic-exposed and sporadic cases. RESULTS: Thirty-six persons (21 male, 15 female; mean age, 57 years) participated, all of whom had been exposed to the asthma medication early in life (mean age, 13 years) for a mean duration of 5 years. Each person had at least one cutaneous sign of chronic arsenicism, either self-reported or on examination, and all except one had a history of either BCC or squamous cell carcinoma of the skin, with self-reports of 20 to 2000 skin lesions removed per person. The mean age at first presentation with a BCC was 33 years, but neither latency nor number of skin lesions appeared to be related to duration of exposure to arsenic. BCCs in persons exposed to arsenic occurred more often on sun-protected sites compared with BCCs in age- and sex-matched sporadic cases (P <.001), but the distribution and histologic subtypes between these two groups were similar. CONCLUSION: We have described BCCs in arsenic-exposed Australians and shown that they occur predominantly in sun-protected locations. Although the reported number of skin lesions is very high, the latency and number do not appear to be related to the duration of arsenic exposure. The histologic types of the BCCs occurring in arsenic-exposed persons are not different from sporadic BCCs.

The spectrum of patched mutations in a collection of Australian basal cell carcinomas.

Inactivating mutations in the human patched (PTCH) gene have been identified in both familial and sporadic basal cell carcinomas (BCCs). In some tumors mutations have been detected in both alleles thereby supporting the role of PTCH as a tumor suppressor gene. We have analyzed 22/23 coding exons of PTCH for mutations in 44 sporadic BCCs, and detected 10 novel mutations in nine tumors. In two of the mutant tumors the remaining allele was inactivated by loss of heterozygosity. Five novel PTCH polymorphisms were also identified. Most of the variations found were C>T substitutions at dipyrimidine sites, supporting previous studies which indicate a role for ultraviolet-B in the genesis of sporadic BCCs.

Expression of p53 in arsenic-related and sporadic basal cell carcinoma.

BACKGROUND: The TP53 gene has been shown to have an important role in the genesis of sporadic, presumably mainly sunlight-related, basal cell carcinoma (BCC). However, its role in arsenic-related BCCs is not clear, although the trivalent form of arsenic has been long recognized as a cause of BCC. Arsenic treatment has been shown to cause hypermethylation of the TP53 gene in lung carcinoma cell lines, but it is not known if this occurs in vivo in arsenic-related BCCs. OBJECTIVE: To compare the immunohistochemical expression of the p53 protein in arsenic-related and sporadic BCCs to determine if the expression pattern is consistent with gene silencing. SETTING: A research institute and hospital in Australia. CASES: One hundred seventeen white patients with 121 sporadic BCCs and 21 white patients with 92 arsenic-related BCCs. MAIN OUTCOME MEASURES: The expression and the intensity of p53 were scored semiquantitatively. Statistical analysis was performed using the chi2 test. RESULTS: Arsenic-related BCCs express p53 less often and at a lower intensity than sporadic BCCs (P = .001; 2-tailed test). The BCCs from sun-exposed sites, whether arsenic related or sporadic, more frequently showed overexpression of p53 than those from less-exposed areas (P = .004; 2-tailed test). The more aggressive subtypes of BCC show a higher level of expression of p53 than the less aggressive forms (P = .04; 2-tailed chi2 test). CONCLUSIONS: These results are consistent with the hypothesis that the TP53 gene is down-regulated by methylation in arsenic-related BCC, particularly those from less-exposed sites. However, an alternative possibility is that mutations in TP53 that stabilize the protein are less common in arsenic-related BCCs. Further analysis will be necessary to distinguish between these hypotheses.

Clinical and microbiologic findings in cellulitis in Thai patients.

BACKGROUND: Cellulitis is an inflammation of subcutaneous tissue in which infective, generally bacterial cause is proven or assumed. However, attempts to culture bacteria from lesions are often unsuccessful. METHOD: One hundred and fifty cases diagnosed as cutaneous cellulitis at Siriraj Hospital between 1992 and 1995 were retrospectively studied. RESULTS: Our study in 150 adult Thai patients with cellulitis showed that the most common site of infection was the lower extremity. Forty two per cent of the patients had history of preceding local trauma. Fever and regional lymphadenopathy were detected in 77.3 per cent and 22.6 per cent respectively. Sixty nine per cent of patients had leukocytosis with a mean neutrophil ratio of 79.7 per cent of patients with underlying diseases predisposed to the infection, 61.6 per cent had positive lesional culture results in contrast to 31.6 per cent in patients without. Needle aspiration and blood gave low positive culture yields. The common organisms detected were S.aureus and Streptococcus group A (83%) in immunocompetent patients. Of immunocompromised patients, in one half of the cases gram negative bacteria were found. CONCLUSIONS: This study showed that in immunocompetent patients, the major bacterial isolated in cellulitis were S.aureus and Streptococcus group A. In immunocompromised patients, gram negative bacteria were found in one half. These findings may help in the selection of antimicrobials before the results of bacterial cultures are available or in culture negative cases.

Pruritic papular eruption in HIV seropositive patients: a cutaneous marker for immunosuppression.

BACKGROUND: Previous reports have shown the correlation between certain skin disorders and immune status in human immunodeficiency virus (HIV) infected patients. Pruritic papular eruption (PPE) is the most common cutaneous manifestation in HIV infected patients. The purpose of this study is to define the relationship between the presentation of PPE and the immune status in HIV infection, as measured by the T-cell subset, and to establish the usefulness of this common eruption as a predictor of CD4 count. METHOD: In this cross-sectional study, 20 HIV-positive patients with characteristics of PPE were studied. Clinical data, skin biopsy, and immune status, evaluated by measuring CD4, CD8, and CD4/CD8, were investigated. RESULTS: Seventy-five per cent of patients already had antecedent skin disorders, so PPE is not a leading symptom in HIV infected patients; 81.25% of PPE patients had an advanced degree of immunosuppression with a CD4 count below 100/mm3 and 75% below 50/mm3. CONCLUSIONS: PPE can be regarded as a cutaneous marker of advanced HIV infection.

Phototesting in oriental patients with lupus erythematosus.

Light sensitivity is an important clinical characteristic of several forms of lupus erythematosus (LE). Recently, investigations have been able to induce LE-like lesions in LE patients with UVA as well as UVB, although most of these studies were conducted in Caucasians. Thus, there is insufficient data on phototesting in Oriental patients with LE. The aim of this study was to evaluate light sensitivity in Oriental patients with LE. Fifteen patients with various forms of LE were tested. Patients were evaluated by provocative phototesting, and threshold doses of UVA and UVB radiation that produced erythema and pigmentation were determined. The minimal erythema doses (MED) of UVB, immediate pigment darkening (IPD), and minimal tanning doses (MTD) were within the normal range in LE patients compared to a control group. Skin lesions clinically and histologically compatible with LE were induced in two of six patients with SLE, and four of nine patients with DLE. These lesions developed in about 2 weeks (range 5 to 23 days) after irradiation and lasted approximately 1 to 3 months (47 +/- 24 days). The action spectrum of the induced lesions was within the UVB range in four patients, in the UVA range in one patient, and in the UVB and UVA ranges in one patient. We found no correlation between a positive history for UV sensitivity and phototest reactions. In conclusion, the incidence of positive phototest reactions in Oriental patients with LE seems to be similar to or a little lower than in Caucasians. There was no correlation between a positive history for UV sensitivity and phototest reactions.

Panniculitis in tuberculosis: a clinicopathologic study of nodular panniculitis associated with tuberculosis.

BACKGROUND: Certain types of panniculitis, erythema induratum of Bazin and erythema nodosum, have been well documented as tuberculids. Many histopathologic diagnoses of panniculitis have been reported in tuberculosis patients. This study investigates the correlation between underlying tuberculosis and clinicopathologic findings of panniculitis. METHODS: We retrospectively reviewed the clinical files of histologic-proven panniculitis cases at the Dermatologic Clinic, Siriraj Hospital from January 1992 to December 1995; only cases with active tuberculous foci were analyzed. RESULTS: The incidence of panniculitis caused by tuberculosis was 8.2%. The ratio of men to women was 1:1. The mean age of onset was 35.3 years. The average duration of the nodules was 35.5 days. There was a history of contact tuberculosis in 16.6%. Constitutional symptoms and a strongly positive purified protein derivative (PPD) reaction were found in 66.6%. Chest roentgenograms were abnormal in 83.3%. The erythrocyte sedimentation rate was elevated in all tested cases. The histopathologic diagnoses were nodular vasculitis (33.3%), erythema nodosum (50%), and cutaneous periarteritis nodosa (16.4%). The panniculitis lesion responded to standard antituberculous regimens in 4.6 weeks, on average, with residual hyperpigmentation. CONCLUSIONS: In panniculitis patients, clues for the investigation of tuberculosis included constitutional symptoms, elevated erythrocyte sedimentation rate, and abnormal chest roentgenograms. Histopathologic changes of panniculitis did not seem to correlate with underlying tuberculosis. The clinician should be aware of the tuberculosis, however, and should carefully search for active foci in all panniculitis patients.

Functional interaction of a novel cellular protein with the papillomavirus E2 transactivation domain.

The transactivation domain (AD) of bovine papillomavirus type 1 E2 stimulates gene expression and DNA replication. To identify cellular proteins that interact with this 215-amino-acid domain, we used a transactivation-defective mutant as bait in the yeast two-hybrid screen. In vitro and in vivo results demonstrate that the cDNA of one plasmid isolated in this screen encodes a 37-kDa nuclear protein that specifically binds to an 82-amino-acid segment within the E2 AD. Mutants with point mutations within this E2 domain were isolated based on their inability to interact with AMF-1 and were found to be unable to stimulate transcription. These mutants also exhibited defects in viral DNA replication yet retained binding to the viral E1 replication initiator protein. Overexpression of AMF-1 stimulated transactivation by both wild-type E2 and a LexA fusion to the E2 AD, indicating that AMF-1 is a positive effector of the AD of E2. We conclude that interaction with AMF-1 is necessary for the transcriptional activation function of the E2 AD in mammalian cells.

Is injection of contaminated animal bite wounds with rabies immune globulin a safe practice?

In Asia, it is still controversial whether it is safe to inject a contaminated animal bite wound with a foreign protein such as equine or human rabies immune globulin, even though this is recommended by the World Health Organization. A prospective study of 114 severe animal bite wounds which were injected with equine or human rabies immune globulin revealed an overall incidence of gross infection of 11.4%. No matched control group of patients bitten by animals whose wounds were not injected with immune globulin could be studied in this environment with a high prevalence of canine rabies. The incidence of wound infection in lacerations inflicted by sharp objects and sutured under local anaesthesia was therefore studied prospectively in 100 Thai patients from a similar socio-economic milieu; it was found to be 13%. Wound infection was more common in animal bites and lacerations of the lower extremities. It is concluded that injecting a properly cleansed bite wound with equine or human rabies immune globulin is a safe practice and should be performed whenever there is a possibility that the biting animal might have rabies.