Pattern of skin diseases prompting biopsy before and during the COVID-19 pandemic in Yogyakarta, Indonesia.

INTRODUCTION: Less biopsies were expected when large scale social restrictions were enforced during COVID-19 pandemic. AIM: To compare the skin diseases prompting biopsy before and during the COVID-19 pandemic. MATERIALS AND METHODS: A retrospective study of skin diseases was performed; the skin problems were then grouped into major histopathological reactions. RESULTS: A total of 229 biopsies were performed before the COVID-19 outbreak, whereas only 160 biopsies were done during the pandemic. Before versus during the outbreak, the proportion of major reactions were granulomatous 20.52% vs 21.88%, neoplasms 17.47% vs 20%, psoriasiform 14.85% vs 10%, vesiculobullous 9.61% vs 8.75%, others 10.92% vs 7.50%, interface dermatitis 6.99% vs 10%, vasculopathy 6.99% vs 5.63%, spongiotic 6.55% vs 8.13%, panniculitis 3.49% vs 3.75%, and superficial and deep dermal infiltrate 2.62% vs 4.38%. CONCLUSION: A decreased total number of patients prompting less biopsies were reported during the COVID-19 outbreak. However, the three largest percentages of major histopathological reactions were still similar, namely granulomatous, neoplasms, and psoriasiform.

Contact allergy in Indonesian patients with foot eczema attributed to shoes.

BACKGROUND: Shoe dermatitis is a form of contact dermatitis resulting from exposure to shoes. Allergens and types of shoes responsible may vary depending on manufacturing techniques, climatic conditions and indigenous traditions. This study focuses primarily on as yet unexplored shoe dermatitis cases in Indonesia. OBJECTIVE: To determine the prevalence of shoe dermatitis in the Dermatology outpatient clinic, Sardjito University Hospital, Yogyakarta, Indonesia over a period of 3 years and to identify the responsible allergens. METHODS: All patients meeting screening criteria for possible shoe contact dermatitis were patch tested with the European baseline series, shoe series and additional series based on earlier studies of Indonesian leather and shoe manufacturers; some were also patch tested with their own shoe materials and shoe extracts. RESULTS: Sixty-four (7.1%) of 903 patients with foot skin disorders were diagnosed with shoe dermatitis. Twenty-five (52.1%) of 48 patch-tested patients showed positive reactions to one or more allergens related to footwear. Sixteen patients were patch tested with their own shoe materials; 11 showed positive reactions. The most frequent relevant sensitizers were rubber allergens followed by preservatives, shoe adhesives and leather materials. CONCLUSION: Shoe dermatitis is common in Indonesia. Using three series of patch tests, we identified responsible allergens and patterns of sensitization in Indonesian shoe dermatitis patients.

Associations between HLA-DRB1 alleles and leprosy in an Indonesian population.

To investigate whether the susceptibility to leprosy (type), subclinical infection with Mycobacterium leprae and the antibody response against M. leprae-specific antigens are associated with HLA-DR phenotypes sequence-specific oligonucleotide HLA-DRB1 and DQA1 typing and antibody assays have been performed in 79 leprosy patients (41 TT/BT and 38 LL/BL) and 50 healthy controls from a Javanese population in Yogyakarta, Indonesia. DRB1*02 was associated with LL/BL [odds ratio (OR) 2.54, 95% confidence interval (CI) 0.97-9.78, p = 0.037 and attributable risk (AR) 41.5%] but not with TT/BT leprosy (p > 0.05). HLA-DRB1*12 was negatively associated with leprosy (either LL/BL or TT/BT [OR 0.33-0.35, p < 0.05, prevented fraction (PF) 58.8%-65.3%]. No significant association was found between HLA-DRB1 or DQA1 type, anti-M. leprae antibody level and subclinical infection with M. leprae. These data indicate that in this population susceptibility to lepromatous leprosy is associated with HLA-DRB1*02, while resistance to leprosy is associated with HLA-DRB1*12. These associations are not paralleled with associations of the same HLA types with anti-M. leprae antibody level. Finally, the results of this study also support the notion that infection with M. leprae per se is not associated with HLA-DRB1 or DQA1 alleles.

Humoral and cellular immune reactivity to recombinant M. leprae antigens in HLA-typed leprosy patients and healthy controls.

In our search for Mycobacterium leprae antigens that might specifically induce immunity or immunopathology, we have tested both humoral and cellular immune reactivity against purified recombinant M. leprae antigens in 29 paucibacillary (PB), 26 multibacillary (MB) leprosy patients, and 47 matched healthy contacts. The following M. leprae antigens were tested: 2L-1 (65L-1, GroEl-1), 2L-2 (65L-2, GroEl-2), 4L (SoDA), 43L, 10L (B) and 25L (Sra). The individuals were also typed for HLAD-RB1 and DQB1 in order to see whether leprosy status and/or immune reactivity to these antigens might be associated with certain HLA types. We also tested sera from another 48 patients before, during and after multidrug therapy (MDT) to study the relationship between antibody reactivity to recombinant M. leprae antigens and MDT. Antibody titers to the four recombinant M. leprae antigens tested and to D-BSA were higher in MB patients compared to PB patients and healthy controls, and declined with treatment. From a diagnostic or monitoring point of view none of the recombinant antigens seemed to be an improvement over D-BSA, mainly due to the lower sensitivity. IgG subclasses were measured in positive sera of untreated patients. These were mainly of the IgG1 and IgG3 subclasses, but subclass diversity was also observed and antigen dependent: all four subclasses could be detected against 10L (B), only IgG1 and IgG3 against 43L and only IgG1 against 25L and 2L-1. Cellular immune reactivity against the purified recombinant M. leprae antigens was measured in a lymphocyte stimulation test (LST). As for M. leprae, there was an inverse correlation between antibody and T-cell reactivity. However, the number of LST responders to recombinant antigens was much lower than to M. leprae. The 43L antigen was recognized most often (19%-24% of individuals tested) and more often than the 10L (B) antigen (10%-12%). No clear correlation was observed with leprosy type or protection and, in general, M. leprae nonresponders were also negative with recombinant antigens. Finally, we confirmed that HLA-DRB1*02 is associated with leprosy in this population, and we observed an association between DQB1*0601 and lepromatous leprosy. The number of positive individuals was too small to allow a meaningful analysis of the relationship between HLA type and immune reactivity. Although these data do not allow a conclusion as to one of these purified recombinant antigens being either protection or disease related, the antigen-dependent IgG subclass diversity warrants further study on antigen-specific qualitative differences in immune reactivity that may be relevant for the outcome of an infection with M. leprae.

A seroepidemiological study of leprosy in high- and low-endemic Indonesian villages.

A seroepidemiological study was performed in three different leprosy-endemic areas in Indonesia, including two isolated villages with high endemicity in South Sulawesi (Kaluarang and Hulo) and an area with low endemicity in Java (Jepara). A total of 2430 serum samples were collected from 2672 individuals in these locations. The prevalence of leprosy in these three areas, as determined during this study, was 29/1000, 11/1000, and 7/1000 in Kaluarang, Hulo and Jepara, respectively. Two serological assays were employed in this study to detect antibodies against Mycobacterium leprae. One is an enzyme-linked immunosorbent assay (ELISA) based on the detection of antibodies to the species-specific epitope of phenolic glycolipid-I (PGL-I) of M. leprae. The second test, using inhibition of an ELISA reaction (ELISA-INH) detects antibodies to a species-specific epitope on the 36-kDa protein antigen of M. leprae. In comparison with clinical findings, the specificity of both serological tests was calculated to be 91%. The sensitivity of the ELISA was 97.6% for multibacillary (MB) cases and 56.8% for paucibacillary (PB) cases; for the ELISA-INH, it was 97.6% and 81.8% for MB and PB cases, respectively. Seropositivity rates were shown to be unrelated to sex, to Mitsuda skin-test reactivity, or to BCG vaccination status. The pattern of seropositivity was, however, clearly age-related, with high seropositivity in the age group 10-19 years and decreasing rates of positivity in the older age groups. Age-standardized seropositivity ratios were not correlated to the prevalence of leprosy when comparing the three areas. Therefore, it is not yet clear whether or not seropositivity reflects infection. If it does, other, as yet unidentified, factors may play a role in the natural history of the disease.

Mycobacterium leprae-specific T cells from a tuberculoid leprosy patient suppress HLA-DR3-restricted T cell responses to an immunodominant epitope on 65-kDa hsp of mycobacteria.

The polar tuberculoid type (TT) of leprosy, characterized by high T cell reactivity to Mycobacterium leprae, is associated with HLA-DR3. Surprisingly, DR3-restricted low T cell responsiveness to M. leprae was found in HLA-DR3-positive TT leprosy patients. This low responsiveness was specifically induced by M. leprae but not by M. tuberculosis and was seen only in patients and not in healthy controls. We studied this patient-specific, M. leprae-induced, DR3-restricted low T cell responsiveness in depth in one representative HLA-DR3-positive TT leprosy patient by using T cell clones. From this patient two types of T cell clones were obtained: one type was cross-reactive with M. tuberculosis and recognized an immunodominant epitope (amino acids 3 to 13) on the 65-kDa heat shock protein (hsp) the other type was M. leprae specific and reacted to a protein other than the 65-kDa one. To examine whether these M. leprae-specific T cell clones were responsible for the DR3-restricted low responsiveness to M. leprae, we tested them for the ability to suppress the proliferation of the DR3-restricted, 65-kDa, hsp-reactive clones. The DR3-restricted, M. leprae-specific T cells completely suppressed the proliferative responses of DR3-restricted, cross-reactive T cell clones to the 65-kDa hsp from the same patient as well as from other individuals. Also, DR3-restricted responses to an irrelevant Ag were suppressed by the M. leprae-specific T cell clones. However, no suppression of non-DR3-restricted T cell responses was seen. Although the mechanism must still be elucidated, this M. leprae-induced, DR3-restricted immunosuppression may at least partly explain the observed DR3-associated low T cell responsiveness in TT leprosy patients.