Tender cutaneous nodules of the legs: diagnosis and clinical clues to diagnosis.

BACKGROUND: "Tender cutaneous nodules of the legs" is a common manifestation in dermatology. Histopathological investigation is usually required for this condition, because clinical data are frequently insufficient to make a definite diagnosis. OBJECTIVE: To identify and analyze the causes of patients presenting with tender leg nodules and to reveal clinical clues that could help to differentiate causes. MATERIALS AND METHODS: The medical records and histopathological slides of patients presenting with tender cutaneous nodules of the legs between January 2005 and December 2007 were retrospectively reviewed. RESULTS: Of the total of 154 patients, 122 (79.2%) were female. Definite diagnoses were categorized into four groups: inflammation (84.4%); infection (5.8%); tumor (6.5%); and nonspecific (3.2%). The most common cause in the inflammation group was erythema nodosum. The infections found were Acremonium spp., Penicillium sp., Mycobacterium abscessus, Mycobacterium fortuitum and Mycobacterium leprae. The tumors included leiomyoma, leukemia cutis, and lymphomas. Clinical data that correlated with and could be used as clues for the inflammation group were female sex (P = 0.03, OR 6.43) and lower leg involvement (P = 0.03, OR 7.14). LIMITATIONS: The retrospective manner of this study is a limitation. CONCLUSION: Various inflammatory conditions, infections, and tumors can present as tender cutaneous nodules of the legs. Female sex and lower leg involvement were clinical data that could be used as clues for the diagnoses in the inflammation group. However, histopathological investigation is still crucial to determine a definite diagnosis in patients presenting with tender cutaneous nodules of the legs.

Cutaneous anaplastic large cell lymphomas: a report of 9 cases from Thailand.

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is one type of lymphoma, which is characterized by the proliferation of pleomorphic large atypical lymphoid cells expressing CD30 antigen. ALCL involving skin can be either primary cutaneous disease or cutaneous involvement secondary from systemic disease. Data of clinical manifestation of cutaneous ALCL in Thai patients is limited. ALCL in Thai patients may differ from other groups of patients. OBJECTIVE: To study the clinical manifestation of cutaneous ALCL in patients of Faculty of Medicine Siriraj Hospital, Thailand. MATERIAL AND METHOD: Medical records of nine patients with histopathologic diagnosis of ALCL from skin biopsy at Faculty of Medicine Siriraj Hospital were reviewed. RESULTS: Of nine patients, four patients were diagnosed as primary cutaneous ALCL, four patients as systemic ALCL with secondary skin involvement, and one patient as combined primary cutaneous ALCL and lymphomatoid papulosis. Three primary cutaneous ALCL patients had no recurrence of disease during 6-year follow-up. However all systemic ALCL patients died at one day to 1.5 years after diagnosis. CONCLUSION: Clinical manifestation and clinical course of Thai patients with anaplastic large cell lymphoma corresponded with the data from other patient population.

Current status of the research ethics committees in Thailand.

BACKGROUND: Many research ethics committees (RECs) have been established to review biomedical research involving human subjects in many research institutes. The purpose is "To protect rights and welfare of human research participants". It is necessary to determine how many research ethics committees have been established in Thailand and whether they have a high enough standard toprotect the rights and welfare of human research subjects. OBJECTIVE: To determine the status of research ethics committees in Thailand. MATERIAL AND METHOD: One hundred thirty survey questionnaires were distributed by mail to medical schools of universities, public hospitals under the Ministry of Public Health, private hospitals, and research institutes. RESULTS: Seventy-eight questionnaires were returned. Thirty respondents had standard Operating Procedures (SOP). Twenty-two RECs had their own office while 36 had to share the office with other departments or units. Board meeting frequency was once a month. The average number of committee members was 14 and the majority was scientific members. Absence of nonaffiliated members was found in RECs (20.6%). Thirty RECs had never provided training for REC members and investigators, the other 48 provided training at least once a year Decision are made by consensus in 51 and majority vote in 14 RECs. Twenty-two respondents managed conflicts of interest (COI) by asking those members to leave the meeting before a decision was finalized. Thirty-nine RECs required continuous review after approval of the protocols. CONCLUSION: Strong support from the organization leader is a key factor to efficiency and high standards of REC operation. Developing a network of RECs will be useful for future development. REC members still need knowledge to better protect the rights, safety, and well-being of research participants.

TNF alpha and NRAMP1 polymorphisms in leprosy.

OBJECTIVE: To determine the association of TNF alpha and NRAMP1 polymorphisms in leprosy. MATERIAL AND METHOD: The polymorphisms of TNF alpha at -238, -308, and NRAMP1 at INT4, D543N, and3' UTR were examined in 37 patients with leprosy (24 multibacillary and 13 paucibacillary) and 140 healthy controls. PCR-SSP and PCR-SSO method were used to type TNF and NRAMP1 polymorphisms. RESULTS: The genotype frequency of TNF-308 G/A was significantly increased in all leprosy patients compared to the controls (p = 0.04, OR = 2.69). When leprosy types were divided, the allele frequency of TNF-308A was significantly increased in multibacillary leprosy compared to the normal controls (p = 0.04, OR = 2.93). There was no significant difference in the distribution of the genotypes and allele frequencies of TNF -238 and NRAMP1 polymorphisms between the patients and controls. CONCLUSION: TNF-308A was associated with susceptibility to multibacillary leprosy.

Detection and identification of Mycobacterium species by polymerase chain reaction (PCR) from paraffin-embedded tissue compare to AFB staining in pathological sections.

BACKGROUND: Polymerase chain reaction (PCR) is a recent, rapid and reliable method in the detection of causative organism. The authors tried to determine the possibility of using PCR technique as an alternative way to detect mycobacterial DNA from paraffin-embedded tissue to avoid repeated biopsy from the patient. MATERIAL AND METHOD: Paraffin-embedded tissue blocks, the corresponding histopathologic slides, and cultural results were retrospectively searched for according to the patient's records, the granuloma clinic, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand from 1994-2000. One hundred and thirty-one tissue blocks and slides were found but only 120 cultural results were retrieved Histologic sections were reviewed for AFB findings and PCR was done using 16S rRNA sequences to detect M. tuberculosis by one-tube nested technique and multiplex PCR for M. marinum and M. fortuitum complex. RESULTS: The causative organisms were identified by AFB staining in pathologic sections 31.29%, by PCR 35.87%, and by culture 30.00% of tested samples. The sensitivity of PCR when compared to AFB result was 29.26%, specificity 61.11% but when compared to cultural results, the sensitivity of PCR was 66.67% and AFB sensitivity was 41.66% with specificity 76.19% and 72.61% respectively. CONCLUSION: The low sensitivity of the PCR method may be due to formalin fixation, deparaffinization process, DNA extraction method, the use of 16S rRNA-based primers and the length of the expected product, and the tissue type that may have Taq polymerase inhibitor. Therefore, PCR should be used to augment the information of the conventional method in the diagnosis of mycobacterial infection.

Mycobacterial skin infections: comparison between histopathologic features and detection of acid fast bacilli in pathologic section.

BACKGROUND: Detection of acid fast bacilli (AFB) in chronic granulomatous inflammation is an important clue for mycobacterial infection. DESIGN: A retrospective review of 104 pathologic sections (from 1994 to 2001) of suspected cases of mycobacterial (tuberculous and nontuberculous) skin infections to study histopathologic features and the correlation with the presence of AFB in the section was performed. RESULTS: All cases showed granulomatous inflammations that can be categorized into 4 types: mixed cell, suppurative, tuberculoid and palisading granuloma. AFB was found in 32 sections (30.77%). Ninety five specimens from 104 specimens were simultaneously cultured. AFB positive cases yielded higher positive cultural results, 17 from 29 cases (58.62%) compared to the AFB negative group, 23 from 66 cases, (34.85%). Mixed cell granuloma was the most common histologic feature, but suppurative granuloma was the most common histological feature (56.25%) in which AFB could be found, which was statistically significantly different from other types of granuloma. Tuberculoid granuloma was more common in the AFB negative group (20.83%) compared to the AFB positive group (9.37%) but the difference was not statistically significant. In cases that AFB could not be found, the inflammation tended to be located in the upper half of the dermis. CONCLUSION: AFB can be more frequently detected in suppurative granuloma that might be located in any portion of the dermis. This finding was not species specific.

Cutaneous leukocytoclastic vasculitis: the yield of direct immunofluorescence study.

BACKGROUND: Leukocytoclastic vasculitis (LCV) is a clinico-pathological entity. Previous direct immunofluorescence study (DIF) studies of vasculitis showed positive findings mainly in the early stage of the disease. OBJECTIVE: To study the positive yield and patterns of DIF in patients with various stages of LCV. DESIGN: One hundred patients with LCV who attended the Department of Dermatology, Siriraj Hospital from 1997 to 2000 were enrolled in the study. RESULTS: The study showed immunoreactive deposits in blood vessel walls in 76 cases (76%). Forty seven per cent of patients showed immunoreactant deposit only in superficial blood vessel walls, 3% had deposits only in deep blood vessel walls. Superficial and deep blood vessel wall deposits were seen in 26%. Dermo-epidermal deposit in addition to blood vessel wall deposit was found in 39%. The most common immunoreactive deposit was C3 (71%), followed by IgM (35%), IgA (12%) and IgG (8%) respectively. The age of the skin lesions at the time of biopsy ranged from 1 to 7 days. 82% of patients with one day old lesions showed immunoreactive deposits in the blood vessel walls and 74% of the group with lesions aged 2-7 days at the time of biopsy showed immunoreactive deposits in the blood vessel walls. CONCLUSION: The present study showed a 76% positive yield for DIF study in patients with LCV when biopsies were performed within one week of onset. There was a tendency for the percentage of positive DIF results to decline when the biopsy was performed on lesions that were more than 1 day old.

Gender differences in epidemiological factors associated with treatment completion status of leprosy patients in the most hyperendemic district of Nepal.

The introduction of multidrug therapy (MDT), recommended by WHO, has been a major advance in the treatment of leprosy because of its relatively short treatment course and low rate of relapse. Although leprosy treatment is provided to both sexes equally, in most parts of the world significant differences have been found in treatment status. The main objective of the study was to investigate gender differences in epidemiological factors associated with treatment status of leprosy patients. An analytic cross-sectional study was carried out in the most hyperendemic Dhanusa District, Nepal. Stratified random sampling was applied for selection of the patients. Statistical analysis of the differences in treatment status, between males and females, and among other epidemiological factors of interest was carried out using multiple logistic regression. Chi-square/Fisher's exact test were also used to assess significant differences in values between males and females. There were 580 leprosy patients (385 male and 195 female) aged >15 years registered for MDT between April 1, 2001 to March 31, 2002 in the 16 main health centers of the district. Of the 580 patients, a total of 273 (183 male and 90 female) were included in the study, to collect data on clinical type of leprosy, patterns of physical deformity/disability, site of skin lesions, and socio-demographic information. There were 183 male (68.3% on MB-MDT) and 90 female (61.1% MB-MDT) leprosy patients. We found that 79.2% of male patients completed treatment, while 34.4% female patients did not complete within the given time frame. Significant gender differences among leprosy patients were found in the distribution of disability grades and treatment completion status. However, there was no significant gender difference in the distribution of leprosy types and skin lesion sites. The study also found significant associations between treatment completion status and gender (adjusted OR 2.05, 95% CI: 1.07-3.94), educational status (adjusted OR 2.37, 95% CI: 1.12-4.99), disability grade I (adjusted OR 3.14, 95% CI: 1.23-8.04), and disability grade 0 (adjusted OR 2.92, 95% CI: 1.14-7.47) after adjustment for all other leprosy/demographic factors.

Gender difference in socio-epidemiological factors for leprosy in the most hyper-endemic district of Nepal.

Leprosy which has caused stigma and social ostracism for millennium is nearing elimination worldwide as a public health problem, but the leprosy burden in Nepal is still 4.4 times greater than WHO's target level of less than one case per 10,000 population. Although leprosy affects both the sexes, in most parts of the world males are affected more than females at a ratio of 2:1. The general objective of the study was to investigate the gender difference in socio-epidemiological factors for leprosy. The analytic cross-sectional study was carried out in one of the most hyper endemic district- Dhanusa district of Nepal. Stratified random sampling method was applied for the selection of the patients. Chi-square/Fisher's exact test was applied to assess statistically significant differences in values between males and females. There were 580 leprosy patients (385 male and 195 female) aged above 15 years registered for multi drug therapy between April 1, 2001 to March 31,2002 in the 16 main health centers of the district. Out of 580 patients, 273 patients (183 males and 90 females) were included in the study in order to collect the data on socio-demographics, patient's knowledge on leprosy, treatment seeking behaviour, and social problems faced by the patients. Data were collected using a structured interview schedule. The mean age of the male patients was 45.1 years (range 15-77 years) and female patients were 40.3 years (range 15-75 years). Among male patients 93.4% were married while among female patients 70.0% were married. Among male patients 51.9% were illiterate whereas 71.1% were illiterate among female patients. Most of the patients (69.6%) lived in joint family and the rest in nuclear family. Among male patients, 86.9% had good knowledge about the disease compared to 73.3% among females. This study showed that among the female patients 12.2% were facing high level of social problems, while among male patients only 4.4% were facing the same. About 15% patients had poor treatment seeking behaviors (8.2% among males and 27.8% among females). A significant gender differences among leprosy patients have been found in age distribution, educational status, marital status, caste types, family members, and overall knowledge on the general aspect of leprosy, social problems faced by the patients and treatment seeking behaviour.

Nontuberculous mycobacterial skin infections: clinical and bacteriological studies.

OBJECTIVE: Nontuberculous mycobacterial (NTM) skin infections were analysed in terms of clinical manifestation in different species to provide clues for the clinical diagnosis and sensitivity patterns of these species were studied for planning appropriate therapy. DESIGN: A retrospective study was performed in 123 suspected cases of NTM infections from January 1994 to December 2000. NTM infection was documented by culture result of the infected tissue obtained by skin biopsy. Drug susceptibility test was done as requested. RESULT: Rapid growers (M. fortuitum-chelonae) were found in 26 cases (65%) and M. marinum was responsible for 12 cases (30%) and caused only localized skin lesions on arms or legs as indurated plaque, Disseminated skin infections manifested as multiple abscesses were found in 2 cases caused by M. avium in an HIV-infected male patient and mixed infection of M. szulgai and M. terrae in an immunocompetent female patient after a dental procedure. Both sexes were affected equally in overall number but male predominated in M. marinum infection and females predominated in rapid growers. All ages can be affected but most cases were middle aged. Scrofuloderma-like cervical lymphadenitis and cutaneous abscesses were the common manifestation of rapid grower infections. Hyperkeratotic verrucous plaques (tuberculosis verrucosa cutis-like) and sporotrichoid lesions were the common manifestations of M. marinum infection. M. marinum is sensitive to minocyclin, clarithromycin, amikacin, rifampicin and ethambutol and a good clinical response was obtained with doxycyclin 100 mg orally twice a day for 3 months. Clarithromycin and amikacin showed in vitro activity against the same strain of M. fortuitum but most strains of rapid growers resisted antituberculous drugs and also various antibiotics. CONCLUSION: Clinical manifestations can be used as clues for diagnosis. Medical therapy is recommended for M. marinum infection and surgical treatment is recommended for rapid growers.

Scrofuloderma and Sweet's syndrome.

BACKGROUND: In recent years, the rare association of Sweet's syndrome with nontuberculous mycobacterial lymphadenitis has been reported. OBJECTIVE: To report the clinical, demographic, and bacteriologic data and association with Sweet's syndrome of 18 patients with scrofuloderma and scrofuloderma-like condition caused by nontuberculous mycobacterial infections seen during the past 7 years (1994-2000). METHODS: In all patients, a biopsy specimen was obtained for histopathologic and microbiologic studies. Patients from whom Mycobacterium tuberculosis and nontuberculous mycobacteria were isolated from the culture of skin biopsy specimens were included. Deep fungal infection was excluded by the lack of a fungal element in histologic section and cultural methods. The patients were treated with antimicrobials or antituberculous drugs according to the causative species. RESULTS: Eighteen cases of scrofuloderma (nine male, nine female; mean age, 36.9 years) were found among 104 patients with cutaneous tuberculosis and nontuberculous mycobacterial cutaneous infections. Sixteen of the 18 cases had lymphadenitis as the underlying focus of scrofuloderma: 15 cases occurred in the cervical group and one case in the inguinal area. One case drained from the soft tissue and one from the paranasal air sinus. Five cases had multiple episodes of Sweet' s syndrome during the course of treatment. Most cases in this group (four of the five) were middle-aged women with cervical lymphadenitis, and the most common species were rapid growers. CONCLUSIONS: Age, sex, and the site of infection may have some influence on the association with Sweet's syndrome in nontuberculous mycobacterial infections.

Analizamos las historias clínicas de 104 pacientesque acudieron a la Clínica Granuloma, DepartamenEscrofuloderma y síndrome de Sweet / Scrofuloderma and Sweet's syndrome

Antecedentes: En los últimos años se ha publicado una rara asociación entre el síndrome de Sweet y la linfadenitis micobacteriana no tuberculosa. Objetivo: Documentar los datos clínicos, demográficos y bacteriológicos y la asociación con el síndrome de Sweet de 18 pacientes con escrofuloderma y enfermedades parecidas a la escrofulodermia debidas a infecciones micobacterianas no tuberculosas observadas durante los últimos 7 años (19942000).Métodos: Se recogió una muestra de biopsia de todos los pacientes para realizar los análisis histopatológicos y microbiológicos. Se incluyeron en el estudio los pacientes en los que se aislaron Mycobacterium tuberculosis y micobacterias no tuberculosas de las muestras de biopsia de piel cultivadas. Se excluyó la infección fúngica profunda por falta de elementos fúngicos en la sección histológica y en los métodos de cultivo. Los pacientes se trataron con antimicrobianos antituberculosos, en función de la especie causante. Resultados: Se encontraron 18 casos de escrofuloderma (9 hombres, 9 mujeres, edad promedio 36,9 años) entre 104 pacientes con tuberculosis cutánea e infecciones cutáneas micobacterianas no tuberculosas. Dieciséis de los dieciocho casos tenían linfadenitis como foco subyacente de la escrofuloderma: se produjeron 15 casos en el grupo cervical y 1 caso en el área inguinal. En un caso se observó drenaje de tejidos blandos y en otro, del seno paranasal. En 5 casos hubo episodios múltiples de síndrome de Sweet a lo largo del tratamiento. La mayoría de los casos de este grupo (4 de 5) eran mujeres de edad intermedia con linfadenitis cervical y las especies más frecuentes eran de cultivo rápido. Conclusiones: La edad, el sexo y la zona de infección pueden tener alguna influencia en la asociación de infecciones micobacterianas no tuberculosas con el síndrome de Sweet (AU)