Teledermatology to Improve Access to and Quality of Skin Care in Eastern Indonesia.

Skin diseases are a major public health concern in Indonesia, although access to specialized care in remote areas is limited. We initiated a low-cost teledermatology service in Sumba, a remote island in eastern Indonesia. Eighteen healthcare workers (HCWs) at five primary healthcare centers received training to manage common skin diseases and submit clinical cases beyond their expertise to an online platform. Submitted cases were reviewed by at least one dermatologist. Diagnostic agreement between HCWs and dermatologists was calculated. The HCWs participated in a satisfaction survey 2 years after project initiation. Since October 2020, of 10,384 patients presenting with skin complaints in a 24-month period, 307 (3%) were submitted for a teledermatology consultation. The most frequent skin diseases were infections and infestations (n = 162, 52.8%) and eczematous (85, 27.7%) and inflammatory (17, 5.5%) conditions. Fifty-three patients (17.3%) were diagnosed with a neglected tropical skin disease, including leprosy and scabies. Dermatologist advice was provided within a median of 50 minutes (interquartile range, 18-255 minutes), with 91.9% of consultations occurring within 24 hours. The diagnostic agreement level between HCWs and dermatologists significantly improved over time, from 46.9% in the first 6-month period (κ = 0.45; 95% CI, 0.37-0.54) to 77.2% in the last 6-month period (κ = 0.76; 95% CI, 0.67-0.86; global P < 0.001). The HCWs reported that the teledermatology service was extremely/very useful in supporting daily practice (100%) and improved their knowledge of skin diseases tremendously/a lot (92%). Teledermatology can improve accessibility and quality of skin services in medically underserved areas, providing opportunities for scalability and knowledge transfer to frontline HCWs.

Cutaneous Manifestation in COVID-19: A Lesson Over 2 Years Into the Pandemic.

Cutaneous manifestations related to Coronavirus Disease-19 (COVID-19) have been reported over 2 years since the pandemic began. This research aimed to review articles published in English that describe cutaneous manifestations related to COVID-19/SARS-CoV-2. A data search for case reports, original studies, and review articles from the onset of the current COVID-19 pandemic to December 31, 2022, was performed using PUBMED, Cochrane Library, ResearchGate, and Google search engines. Keywords were "coronavirus", "novel coronavirus 2019", "COVID-19", "SARS-CoV-2", and "2019-nCoV" in combination with "cutaneous", "skin" and "dermatology" The extracted data included authors, region, sex, age, number of participants with skin signs, cutaneous signs, its location, symptoms, extracutaneous/associated symptoms, suspected or confirmed status for COVID-19, timeline, and healing duration. Six authors independently reviewed the abstracts and full-texts to identify publications providing these details concerning cutaneous manifestations related to COVID-19. A total of 139 publications with full text (122 case reports, 10 case series, and 7 review articles) that reported cutaneous manifestations were identified, and reviewed from 5 continents. The most common cutaneous manifestations of COVID-19 were maculopapular, followed by chilblain-like lesion, urticarial, livedoid/necrotic, vesicular, and other/non-descript rashes/skin lesions. After 2 years into the COVID-19 pandemic, we can conclude that there is no pathognomonic cutaneous manifestation of COVID-19, since it can be also found in other viral infections.

Lupus panniculitis: a rare bilateral and symmetrical manifestation of cutaneous lupus erythematosus in an adolescent girl.

Lupus panniculitis is included in the chronic cutaneous lupus erythematosus group. An 18-year-old female patient came with the complaint of lumps on her face. When she was 16 years old, the patient started to complain about lumps on her right lower arm. Lumps were observed on her left cheek and right chin during the ongoing treatment. Histopathology results showed lymphocyte infiltration in between lobular adipocyte with fibrotic and fat necrosis in the subcutis. Lupus panniculitis lesions in this patient were found both on her face and on her lower arms, which are not considered common predilection sites of lupus panniculitis. The skin lesion observed in this patient was also bilateral and symmetrical, which was a rare finding.

Occupational skin dermatoses among health care workers: A review of adverse skin reactions to personal protective equipment.

Occupational skin-related problems include dermatoses caused by agents in the working environment. For health care workers, these occupational dermatoses could be due to usage of Personal Protective Equipment (PPE), such as gloves, masks, goggles, and other protective equipment. These PPE contribute to both allergic and irritant contact dermatitis. This review summarized the skin damage after PPE usage and hand hygiene protocol. Recommendations should be established to prevent these occupational dermatoses from PPE usage.

Modified Non-Cultured Cell Spray Induced Epithelization in LAMB3 Mutation Epidermolysis Bullosa.

Background: Autologous non-cultured cell (ANCC) spray has been used to treat burns, chronic wounds, and vitiligo, but its use in junctional epidermolysis bullosa (JEB) has not been published previously. Chronic wounds in JEB are caused by mutations of laminin 332 (L322), whose function is to attach and act as a glue in the basal membrane. It is proposed that ANCC applications can provide keratinocytes and fibroblasts required to improve epithelization and spontaneously correct revertant keratinocytes in the wound area. Purpose: To develop a modified procedure of ANCC spray and improve epithelization using silver sulfadiazine covered with plastic wrap to treat chronic wounds of JEB. Patients and Methods: Shave excision of the donor site was performed on a 19-year-old girl with JEB. The ANCC spray was prepared and applied to the chronic wound, which was then covered with silver sulfadiazine occluded with plastic wrap. Results: Following the ANCC spray application, epithelization was successfully initiated. Unfortunately, the wounds recurred after four months of follow-up. Conclusion: The modified application method of ANCC spray provides a good alternative to treat chronic wounds in JEB.

Allopurinol-Induced Stevens-Johnson Syndrome in Javanese Men With Positive HLA-B*58:01.

Background: Allopurinol is the most commonly used drug for the treatment of gout arthritis. However, the use of allopurinol is associated with severe cutaneous adverse reactions (SCARs) and life-threatening immune-mediated reactions that include Stevens-Johnson syndrome (SJS). SJS induced by allopurinol is strongly linked with the presence of HLA-B*58:01 in the Asian population. Such a study has not been conducted in Indonesia. We present two cases with clinical diagnosis of SJS. These patients had Javanese ethnicity, for which evidence on the genetic predisposition of allopurinol-induced SJS/TEN had not been established. Testing for the presence of the HLA-B∗58:01 allele was positive in both cases. Our case report confirms findings from studies in Asian countries that link HLA-B*58:01 and allopurinol-induced SJS/TEN. A larger study is needed to elicit evidence that the HLA-B*58:01 allele can potentially be used as a genetic marker for allopurinol-induced SCARs among different ethnicities in Indonesia.

Acquired Perforating Disorder: A Case with Multiple Underlying Diseases.

A 51-year-old man came to the dermatology and venereology outpatient clinic with the complaint of multiple itchy lumps on his body. The patient had a previous history of hemodialysis due to end-stage renal disease. He also had a previous history of hepatitis B, an abnormal liver function test, and high blood sugar. Histopathological examination with Masson's trichrome revealed that the patient had extrusion collagen in the epidermis which had invagination. Acquired perforating disorder is frequently misdiagnosed as other skin diseases, thus this condition is underdiagnosed. In addition, underlying diseases frequently associated with acquired perforating collagenosis are chronic kidney disease, hepatic insufficiency, and diabetes mellitus. The patient in this case had all 3 conditions. Further investigation is needed to determine whether acquired perforating disorder with multiple underlying diseases will have similar severity with single underlying disease.

The role of gut microbiome in inflammatory skin disorders: A systematic review.

The close relationship between the intestine and the skin has been widely stated, seen from gastrointestinal (GI) disorders often accompanied by skin manifestations. Exactly how the gut microbiome is related to skin inflammation and influences the pathophysiology mechanism of skin disorders are still unclear. Many studies have shown a two-way relationship between gut and skin associated with GI health and skin homeostasis and allostasis. This systematic review aimed to explore the associations between the gut microbiome with inflammatory skin disorders, such as acne, psoriasis, atopic dermatitis, and urticaria, and to discover the advanced concept of this relationship. The literature search was limited to any articles published up to December 2020 using PubMed and EBSCOHost. The review followed the PRISMA guidelines for conducting a systematic review. Of the 319 articles screened based on title and abstract, 111 articles underwent full-text screening. Of these, 23 articles met our inclusion criteria, comprising 13 atopic dermatitis (AD), three psoriasis, four acne vulgaris, and four chronic urticaria articles. Acne vulgaris, atopic dermatitis, psoriasis, and chronic urticaria are inflammation skin disorders that were studied recently to ascertain the relationship of these disorders with dysbiosis of the GI microbiome. All acne vulgaris, psoriasis, and chronic urticaria studies stated the association of gut microbiome with skin manifestations. However, the results in atopic dermatitis are still conflicting. Most of the articles agree that Bifidobacterium plays an essential role as anti-inflammation bacteria, and Proteobacteria and Enterobacteria impact inflammation in inflammatory skin disorders.

Modified tarsorrhaphy versus gold weight implant technique for paralytic lagophthalmos treatment in patients with leprosy: One-year observation of a randomized controlled trial study.

Trial design: This study was a multicenter, Prospective Randomized Open-label Blinded-Endpoint (PROBE) clinical trial, parallel-group study conducted in Indonesia (three sites). Methods: The aim of this study was to compare the effectivity and efficiency of modified tarsorrhaphy (MT) and gold weight implant (GWI) techniques in the surgical treatment of paralytic lagophthalmos in patients with leprosy. The study sample consisted of 23 eyes, with 11 eyes in the MT group and the remaining 12 eyes in the GWI group-the control group. Results: The central eyelid margin distance (lagophthalmos distance) decreased when gentle pressure was applied in the MT (3.09 mm to 0.43 mm) and GWI groups (3.21 mm to 0.83 mm) at postoperative year 1. The Ocular Surface Disease Index score, the tear break-up time, and the Schirmer test without and with anesthesia in the MT and GWI groups showed a p-value of > 0.05. Epitheliopathy improvement occurred in 54.55% of the MT group and 58.33% of the GWI group. Corneal sensitivity change in the inferior quadrant of the MT group (50.00 to 51.30 mm) and in the GWI group (49.61 to 52.93 mm) resulted in a p > 0.05. Postoperative complications occurred in 15% of patients in the GWI group. In addition, the surgery duration of both techniques was similar. Furthermore, the surgery cost in the MT and GWI groups yielded a p < 0.05. Conclusion: The MT technique is as effective as the GWI technique but more efficient than the GWI technique as a surgical treatment for paralytic lagophthalmos in patients with leprosy. Clinical trial registration: [www.ClinicalTrials.gov], identifier [NCT0494 4498].

Novel mutations of epidermolysis bullosa identified using whole-exome sequencing in Indonesian Javanese patients.

Epidermolysis bullosa (EB) is a group of inherited blistering skin diseases known to have heterogenicity of phenotypes and genotypes. There are four main types of EB: simplex, junctional, dystrophic, and Kindler syndrome, which are further classified into 34 distinct subtypes. Twenty different gene mutations are responsible for the loss of function and integrity of the basal membrane zone. In limited-resource settings such as Indonesia, diagnoses of hereditary skin disease often rely on clinical features. This limitation was managed by using the Clinical Diagnostic Matrix EB for clinical diagnosis support and whole-exome sequencing for genetic analysis. This study is the first whole-exome sequencing analysis of Javanese Indonesian patients with EB. The genetic analysis from four patients with EB identified all novel mutations unreported in the dbSNP database. There are Kindler syndrome with FERMT1 frameshift mutation in exon 4, at c.388A (p.I130fs), which causes truncated protein; junctional EB generalized intermediate (JEB-GI) subtype with missense mutation at LAMB3 gene position c.A962C (p.H321P); and recessive dystrophic EB (RDEB) a missense mutation at COL7A1 gene position c.G5000T (p.G1667V). The whole-exome sequencing was further verified by Sanger sequencing. The new mutations' finding is possibly due to the limited genetic database in the Malayo-Polynesian ethnic group. Indonesia has hundreds of ethnic groups, and the Javanese is the largest ethnic group that populates Indonesia. Genetic data of these ethnic groups is important to be established in the international genetic database. This combination of clinical diagnostic and genetic analysis tools with whole-exome sequencing confirmed the challenging diagnosis of epidermolysis bullosa.

COMPARING SOCIO-ECONOMIC CONDITIONS OF MOTHER AND CHILDREN WITH LEPROSY IN ENDEMIC AND NON-ENDEMIC AREAS IN EAST JAVA, INDONESIA.

BACKGROUND: Leprosy is a disease that causes social, psychological, and economic issues. Failure to treat the causes of the immune system dysregulation in endemic areas of leprosy conditions makes the transmission of the bacteria easier. This paper aims to analyze the comparison of family income, occupation types of mothers and fathers, number of children, access to health facilities, and education of mothers, fathers, and children in mothers and children with leprosy in endemic and non-endemic areas. MATERIALS AND METHODS: A cross sectional study by survey was done in both an endemic and a non-endemic area of leprosy in Tuban Regency, East Java, Indonesia. Retrieval of research data was done using interview techniques. Respondents who participated in this study were 106 pairs of mother and child respondents who met the research restriction criteria. Subjects were divided into 5groups based on diagnosis of leprosy and area of living. Bivariate analysis was performed by comparing the independent variables in each group A, B, C, and D with group E. RESULTS: It was found that the variables that differed significantly between the endemic and non-endemic areas were the variable number of children with a p-value=0.004, family income with a p-value=0.049 and the variable mother's education with a p-value=0.016. Meanwhile, other variables do not have significant difference. CONCLUSIONS: We found significant difference on the number of children, father's education, mother's education, and family income. These variables can be a risk factor for leprosy. To make efforts to prevent the transmission of leprosy, stakeholders should consider these factors.

Comparison of IL-17 and FOXP3+ Levels in Maternal and Children Leprosy Patients in Endemic and Nonendemic Areas.

Leprosy, a chronic infection caused by M. leprae, has a complex transmission problem that makes eradication programs difficult. New cases and ongoing transmission of leprosy in endemic areas make individuals living in endemic environments vulnerable to leprosy. This can be caused by the dysregulation of immune system in individuals living in leprosy-endemic areas. Although the number of male leprosy patients is higher, female leprosy patients have more impact on the family health status due to close contact with family members, roles in the household, and parenting. This could cause the increased number of children leprosy patients. We investigated the dysregulation of immune system by comparing IL-17 and FOXP3+ levels occurring in maternal and child leprosy patients in endemic and nonendemic areas. The results of the study found a statistically significant difference in IL-17 levels between the MB leprosy patient group and the control group (p=0.048), where higher levels of IL-17 are observed in the control group. A significant difference also was found in FOXP3+ levels between the group of healthy children living in endemic and those living in nonendemic areas (p=0.047), where higher FOXP3+ is observed in the healthy children living in endemic areas group.

Follicular eruption as a cutaneous manifestation in COVID-19.

A 50-year-old man presented to our dermatology clinic with itchy skin rash. The rash began 5 days after systemic symptoms appeared such as mild fever and mild dyspnoea. The rashes were a characteristic of follicular eruption, which started on his stomach and spread all over his body. After a thorough evaluation, he was diagnosed with COVID-19 and was started on COVID-19 regimens. Skin lesions disappeared on the ninth day of treatment. Our findings contribute to the growing awareness of dermatological manifestations in patients with COVID-19.

Correlation Analysis between Household Hygiene and Sanitation and Nutritional Status and Female Leprosy in Gresik Regency.

Leprosy, also known as morbus Hansen's disease, is a chronic disease caused by M. leprae. Leprosy attacks various parts of the body including nerves and skin. The most important factor in the occurrence of leprosy is the sources of transmission and contact, both from patients and the environment. Household conditions where the person lives and the nutritional status of the individual can be a risk factor for leprosy. Household hygiene and sanitation can be seen from several aspects, like the physical environment of the house, clean water facilities, personal hygiene, availability of latrines, waste disposal facilities, and garbage disposal. This study was aimed to determine the correlation between household hygiene sanitation and nutritional status with females with leprosy in Gresik Regency. This case-control study was conducted in December 2019 in Gresik Regency. The subjects of this study were 74 respondents taken by consecutive sampling techniques. Retrieval of data was carried out using observations from the healthy house component questionnaire, personal hygiene questionnaire, and direct measurement. Data were analyzed using the chi-square test. The results showed significant correlation between physical environment of the house (p=0.001, OR = 0.104), clean water facilities (p=0.008, OR = 0.261), availability of latrines (p=0.018, OR = 0.209), waste disposal facilities (p=0.015, OR = 0.291), and personal hygiene (p=0.001, OR = 2.850) and female leprosy in Gresik Regency. There is no correlation between nutritional status (p=0.085, OR = 0.422) and wastewater disposal waste (p=0.183, OR = 0.486) and female leprosy in this study.

Concurrence of Acrodermatitis Enteropathica and Eczema Herpeticum in a Child with Atopic Dermatitis.

Acrodermatitis enteropathica (AcE) is a rare, autosomal recessive inherited disorder caused by mutation of the SLC39A4 gene coding for zinc transport protein (ZIP 4). The disease appears during childhood especially in breastfeeding or post-breastfeeding infant. Eczema herpeticum refers to a disseminated skin infection of herpes simplex virus that usually leads to vesicular eruptions commonly seen on a background of atopic dermatitis (AD). We describe an 11-year-old boy with periorificial erosions in periorbital, perinasal, perioral, perineal, and gluteal areas, accompanied with itchy vesicles, some covered with hemorrhagic crusts. A clinical diagnosis of AcE and eczema herpeticum with AD was supported by typical lesions and acute and chronic eczematous changes found mainly in the flexural aspects of extremities, which is diagnostic of AD. Laboratory findings showed anti HSV1 IgG (23.43) and high levels of IgE (478.9 IU/L). There was no multinucleated giant cell in the Tzanck test. Skin histology was compatible with AcE. Direct immunofluorescent examination showed no deposits of IgG, IgM, IgA, or complement. Complete resolution occurred within 2 weeks of acyclovir and oral zinc supplementation.

Association between heterozygote Val92Met MC1R gene polymorphisms with incidence of melasma: a study of Javanese women population in Yogyakarta.

Introduction: Melasma is an acquired hypermelanosis of the face. The pathogenesis of melasma is multifactorial and may be caused by interactions between genetics and the environment. Research has shown that skin pigmentation is regulated by the Melanocortin-1 Receptor gene (MC1R). In Japanese populations, Val92Met and Arg163Gln genotypes of MC1R gene polymorphisms are associated with freckles and lentigo solaris, because they have skin types II-III, but for Indonesians who are skin type IV, hyperpigmentation disorders are often melasma. Purpose: This study aimed to identify the association between Val92Met and Arg163Gln genotypes of MC1R gene polymorphisms with the incidence of melasma in a Javanese women population. Patients and methods: This study used unmatched case-control design, conducted by clinical examination and questionnaire. Data were analyzed with Chi-squared test and Odds Ratio (OR). Results: This study evaluated 158 Javanese women from 18-60 years old with 79 case and 79 control subjects. The genotype of Val92Met was found more common in melasma subjects than in non-melasma (p=0.005) with (OR2.53; 95% CI:1.21-5.29). By using a bivariate test we showed sun exposure and family history of melasma were risk factors for melasma (OR:1.99; 95% CI:1.04-3.78) and (OR:35.32; 95% CI:10.25-121.70). However, genotype of Arg163Gln was not a risk factor for the incidence of melasma (OR: 0.86; 95% CI:0.39-1.89). Conclusion: The findings showed Val92Met genotypes, sun exposure and family history were risk factors for melasma incidence. This is the first study on incidence of melasma in an Indonesian population and contributes to ongoing efforts to understand the mechanisms of melasma.

The effect of 5α-oleandrin on keloid fibroblast activities.

BACKGROUND: Keloids develop due to hyperactivity of keloid fibroblast (KF) in proliferation, migration, and collagen deposition along with low rates of collagen degradation. These are a result of the Wnt/ß catenin signaling pathways under stimulation of TGF-ß. 5α-oleandrin can suppress Wnt-targeted genes of osteosarcoma cells. We aimed to evaluate the anti-fibrotic effects of 5α-oleandrin on KF activities. METHODS: We collected the core of keloid materials from six patients who underwent keloid debulking surgery. Passage 4 of KF cells were then treated with mitomycin-C, 5α-oleandrin, and dilution medium as the negative control. To determine the effective dose of 5α-oleandrin, we diluted 5α-oleandrin into various concentrations. The incubation periods were 24 h, 48 h, and 72 h. The anti-proliferation and anti-fibrotic properties were measured using standard assay. RESULTS: Both the mitomycin-C and 5α-oleandrin treated groups indicated decrease in proliferation index (86.16 ± 4.20% and 73.76 ± 4.94%, respectively), collagen deposition index (90.26 ± 1.72% and 71.35 ± 4.26%, respectively), and migration capacity (33.51 ± 1.50% and 28.57 ± 1.58%, respectively). These were significant changes (p ≤ 0.05) compared to the non-treated group. Antifibrotic activities of 5α-oleandrin in cellular proliferation and collagen deposition were better than mitomycin-C. CONCLUSIONS: The 5α-oleandrin has good antifibrotic effect in keloid fibroblast activities.