Phenotype and genotype correlation of inherited epidermolysis bullosa in Indonesia.

BACKGROUND: Inherited epidermolysis bullosa (EB) is a group of genodermatoses with considerable clinical and genetic heterogeneity. Clinical diagnosis of the EB subtypes is frequently imprecise and requires confirmation with genetic testing. There is still limited study using genetic testing to identify EB subtypes in Indonesia. This study aims to identify the pathogenic variants of inherited EB patients at the Department of Dermatology and Venereology, Universitas Padjadjaran-Dr Hasan Sadikin General Hospital in Bandung, West Java, Indonesia and to describe the correlation between the phenotype and genotype of our patients. METHODS: Twelve patients clinically diagnosed with EB were included in this study. Genetic testing was performed in collaboration with KK Women's and Children's Hospital, Singapore. RESULTS: Pathogenic variants were identified in the COL7A1 gene in seven patients, namely Dominant Dystrophic EB (DDEB) with mutation types c.5945G>T, c.6218G>A, Recessive Dystrophic EB (RDEB) c.2005C>T, c.6081dup, c.1268C>T, c.1784C>T which are all known mutations. Novel mutations were found in the COL7A1 gene in two patients namely DDEB c.6253G>T and RDEB c.6740C>T. Two EB Simplex (EBS) patients showed mutation KRT14 gene as c.356T>C, c.373C>T which are known mutation. In addition, a novel mutation in LAMA3 gene c.2649del was found in one Junctional EB (JEB) patient. CONCLUSION: The molecular diagnoses of 12 Indonesian EB patients were identified, of which three were novel pathogenic variants. Concordance between the initial clinical diagnosis and genetic testing was only 33%. This demonstrated the importance of early genetic testing for accurate diagnosis, prognostication, management and genetic counselling.

Self-improving dystrophic epidermolysis bullosa: First report of clinical, molecular, and genetic characterization of five patients from Southeast Asia.

Self-improving dystrophic epidermolysis bullosa is a rare subtype of dystrophic epidermolysis bullosa (DEB) characterized by significant improvement in skin fragility within the first few years of life. Genetic inheritance has previously been reported as autosomal dominant or recessive with both forms harboring mutations in COL7A1. To date, there have been no reports of this rare clinical entity from various Southeast Asian ethnicities. Here, we describe the clinical and molecular features of five patients from the Southeast Asia region who presented with predominantly acral-distributed blisters and erosions in the first few days of life. Blistering resolved over several months, without appearance of new blisters. By immunofluorescence, intraepidermal retention of Type VII collagen was observed in all patient skin biopsies when investigated with antibody staining. Genetic analysis of four patients revealed pathogenic variants in COL7A1 which have not been previously reported. The clinical diagnosis in these rare patients is confirmed with molecular histology and genetic characterization.

Clinical efficacy of dialkylcarbamoylchloride-coated cotton acetate dressing versus combination of normal saline dressing and 2% mupirocin ointment in infected wounds of epidermolysis bullosa.

Dialkylcarbamoylchloride (DACC)-coated cotton acetate dressing works directly through hydrophobic interaction to reduce the number of bacteria without the risk of resistance. It is easy to use and therefore expected to improve patient's compliance. This study aimed to assess the clinical efficacy of DACC-coated cotton acetate dressing compared to a combination of normal saline dressing and 2% mupirocin ointment. A single-blind controlled trial was conducted and included 14 infected epidermolysis bullosa (EB) wounds which were divided into two groups. Group I received DACC-coated cotton acetate dressing, and Group II received the combination of normal saline dressing and 2% mupirocin ointment. Study results showed that the average time required for complete wound closure was 8.6 and 11.1 days in Groups I and II, respectively (p = .014), which was statistically significant. Both groups showed complete bacterial elimination on Day 3 based on negative Gram stain results and on Day 6 based on clearance of clinical manifestations (p = 1.000). This is a novel study in EB-infected wounds, which shows that DACC-coated cotton acetate dressing promotes faster wound closure and is as effective as the combination of normal saline dressing and 2% mupirocin ointment in eliminating bacterial infection.

Clinical efficacy of biocellulose, carboxymethyl cellulose and normal saline dressing in epidermolysis bullosa.

OBJECTIVE: To evaluate the efficacy of a biocellulose, a carboxymethyl cellulose and a normal saline wound dressing in the wound care management of epidermolysis bullosa (EB) skin wounds. METHODS: This was a single-blind, randomised controlled trial involving wounds from patients with EB. Wounds were divided into three groups: group I with biocellulose wound dressing, group II with carboxymethyl cellulose wound dressing and group III with normal saline wound dressing as a control. All dressing changes and wound parameters were recorded. Observations were conducted every three days until complete wound closure or up to one month. RESULTS: The outcomes of treatment of 36 wounds from four patients were evaluated in this study. Mean healing time in group I was seven days, eight days in group II and 14 days in group III. There were significant differences in healing times between group I and group III (p=0.0001) and between group II and III (p=0.001). The results showed a significant reduction in the percentage of wounds area on day three for each group: 51.7% in group I, 51.9% in group II, and 26% for group III. All wounds in groups I and II had healed at day 12 (100%) and at day 24 (100%) in group III. There were significant differences in the reduction of percentage wound area between group I and group III at day three (p=0.044) and day six (p=0.000), and between group II and III at day six (p=0.003). CONCLUSION: The study demonstrates that both the biocellulose and the carboxymethyl cellulose wound dressings significantly reduced percentage wound areas and complete healing times compared with the normal saline wound dressing in EB skin wounds, demonstrating they are both equally good for wound care management in EB patients.

Congenital Triangular Alopecia: A Case of Effective Response with 5% Topical Minoxidil in a Male Adolescent.

Congenital triangular alopecia (CTA) is a rare entity of non-cicatricial alopecia characterized by triangular or oval-shaped alopecia patches on the frontotemporal region of the scalp. Few therapeutic options exist, and there is currently no effective treatment except for hair transplantation. We report the case of an adolescent boy with CTA who was treated with 5% topical minoxidil solution. During therapy, the patient showed improvement in the form of the appearance of terminal hairs, which started to show after two months of treatment. After eight months of treatment, the affected area was fully covered with dense terminal hairs. The patient did not report any adverse reactions/side effects.

A Retrospective Study on the Clinical, Laboratory, and Nutritional Status of Pediatric Epidermolysis Bullosa in a Tertiary Referral Hospital in West Java, Indonesia.

Background: Epidermolysis bullosa (EB) is a genodermatosis disease with bullae and erosions of the skin and mucous membrane that can last for a lifetime and decrease quality of life. Oral and gastrointestinal disorders inhibit the patients' ability to achieve optimal nutrition, making the patients prone to infection, leading to prolonged wound healing, and delayed growth and developmental process. However, there has been no research on the clinical, laboratory, and nutritional status of pediatric EB patients in Indonesia. Purpose: This study aims to describe the clinical, laboratory, and nutritional characteristics of pediatric EB patients treated in Dr. Hasan Sadikin General Hospital Bandung, Indonesia. Patients and Methods: This was a retrospective descriptive study of pediatric EB patient records in Dermatology and Venereology Outpatient of Dr. Hasan Sadikin General Hospital Bandung, Indonesia, from April 2018-March 2020. Results: Study results showed 12 pediatric EB patients consisting of 7 dystrophic EB (DEB) (4 recessive dystrophic EB [RDEB] patients and 3 dominant dystrophic EB [DDEB]), 3 junctional EB (JEB), and 2 EB simplex (EBS). The most extensive EB wounds was found affecting 10-20% of the body surface area with a <10% infected wound area. Pain was found in all patients. The most frequent abnormalities in laboratory examination were anemia and low zinc levels. Severe malnutrition was found in almost half of the patients. Conclusion: RDEB is the most commonly found type of pediatric EB. Wounds on the skin, tooth decay, hand deformity, pain when changing dressings, low zinc levels, and low hemoglobin levels are the clinical features and laboratory findings that contribute to the development of moderate and severe malnutrition in RDEB patients.

Molluscum Contagiosum in HIV Patient Treated with 20% Topical Glycolic Acid After Resistance with Topical Tretinoin.

Molluscum contagiosum (MC) is a benign papular skin infection caused by Molluscum contagiosum virus (MCV). Over the past 30 years, the incidence of MK has continued to increased association with sexually transmitted infections and human immunodeficiency virus (HIV) infection. The incidence of MC in HIV patients is quite high at 5-8%. Until now there is no standard therapy used for the treatment of MC in patients with HIV. In HIV patients, anti retro viral therapy (ARV) is the main therapy with several other additional therapies such as cantaridin, chemical peeling agents such as glycolic acid (20-70%) and trichloroacetic acid (20-100%), cryosurgery, electrosurgery, incision, lactic acid, laser surgery, podophyllin, retinoic acid, and urea. There have been no studies regarding the administration of topical 20% glycolic acid in MC patients. We report a case of MC in an HIV patient who was treated with 20% topical glycolic acid after failing treatment with topical tretinoin. The diagnosis was made clinically, cytologically, and histopathologically, a white mass was found on compression of the lesion and Henderson-Paterson bodies. The lesions on the face, arms, and legs were given glycolic acid lotion 20% which was applied once a day at night. The lesions started to show responses to the treatment at week 6th as some of the MC papules became hyperpigmented macules. The side effects of therapy that appeared were itching and hyperpigmentation. Topical 20% glycolic acid can be used for MC therapy with minimal side effects, easy to apply and safe.

Effectiveness of Pulsed Dye Laser Treatment in Tufted Angioma: A Promising Intervention.

Introduction: Tufted angioma (TA) is a rare benign vascular tumor usually occurring in the first year of life. It may present as reddish papules or purplish red to black plaques. Tender lesions commonly affect the neck, upper trunk, and shoulders. Histologic tufts of capillaries infiltrating the dermis in a "cannon ball" distribution pattern confirm the diagnosis. However, effective treatments for TA are scarce. Pulsed dye laser (PDL) is an alternative therapy for TA, particularly concerning cosmetics and pain relief. This case report demonstrates the effectiveness of PDL as a treatment for TA. Case: We report a 15-year-old girl with five-year history of painful purplish red plaques on her left cheek, neck, chest, left shoulder, and back. Histopathological examination from skin biopsy showed discrete "cannon ball" pattern in the dermis. Laboratory examination revealed normal platelet count and fibrinogen level. Based on these presentations, the diagnosis of TA without complications was made. We treated the lesion using 595-nm PDL with 6.5-10 J/cm2 fluence of, 1.5 ms pulsed duration, and 5-7 mm spot size every three weeks. Reductions in redness and pain were seen after four sessions of treatment. Discussion: PDL promotes selective vascular damage with minimal injury to the surrounding skin. Capillary tufts in TA could therefore serve as a target for laser treatment, which may result in fading redness and pain reduction. Conclusion: PDL is effective in reducing redness and pain in TA.

Xeroderma Pigmentosum with Simultaneous Cutaneous and Ocular Squamous Cell Carcinoma.

Xeroderma pigmentosum (XP) is a rare autosomal recessive disease that disrupts deoxyribonucleic acid (DNA) repair due to ultraviolet (UV) radiation. XP is characterized by extreme sensitivity to sunlight, photophobia, cutaneous lesions in the form of freckle-like hyperpigmented macules, and neoplasia on the skin surface. Malignancy is a common complication found in areas exposed to UV light. Squamous cell carcinomas (SCC) is the most common malignancy seen in patients with XP. This report illustrates a case of XP in a six-year-old girl with cutaneous and ocular SCC. The diagnosis of XP was established based on the patient's history and the presence of typical clinical manifestations. Dermoscopy and histopathology examinations confirmed the presence of SCC on the face and eyes. The management of XP patients includes early diagnosis, lifelong UV protection, and early detection of cutaneous malignancy. Early detection and appropriate management are very important in preventing the occurrence of malignancy.

Retinal Neovascularization in Two Patients with Incontinentia Pigmenti.

Incontinentia pigmenti (IP) is a rare genodermatosis, inherited in an X-linked dominant pattern, making it generally found among women. Among several characteristics of IP are four phases of skin manifestation that tend to follow Blaschko's lines, in addition to abnormalities of the eye, central nervous system (CNS), and teeth. Ocular involvement in IP patients can occur since birth, which can be classified into retinal or non-retinal disorders. Retinal disorders can result in detachment, which is a major ocular threat for IP patients. This article reports two IP cases with overlapped phases of skin disorders in baby girls with ocular manifestations since early life. Clinical signs and additional examination of the skin and eyes are utilized to make the diagnosis. All the features of the histopathological examination supported the diagnosis of IP, and ocular exams revealed abnormalities in the form of retinal neovascularization (RN). Although RN may resolve spontaneously, patients should be monitored for the development of other eye disorders such as visual impairment.

Melatonin and Sleep Disturbances in Children With Atopic Dermatitis.

Objective: To evaluate the correlation between melatonin levels and sleep quality, based on the Children's Sleep Habit Questionnaire (CSHQ), among children with atopic dermatitis (AD). Methods: This was an analytic study with a cross-sectional design involving two groups, AD children as the case group and participants without AD as the control group, conducted at the Pediatric Dermatology Clinic of Dr. Hasan Sadikin Hospital, Bandung, Indonesia. Melatonin levels and CSHQ score in the case group were compared to that in the control group. Correlation analysis was performed between melatonin levels and sleep quality based on CSHQ in the case group. Results: Participants in this study consisted of 19 children with moderate AD, (no patient with mild and severe AD was recruited), and 19 participants without AD. The mean CSHQ score in the case group was significantly higher than the control group (47.84 vs 36.79; p<0.05). The mean melatonin level in the case group was significantly lower than the control group (320.18 pg/mL vs 383.86 pg/mL; p<0.05). Comparative analysis was conducted using independent t-test. There was a significant Pearson's correlation index between SCORAD and CSHQ (p<0.05). However, there was no correlation between melatonin levels and CSHQ, as well as between melatonin levels and SCORAD (p<0.05). Conclusion: Children with moderate AD have impaired sleep quality and lower melatonin levels compared to controls. No correlation was found between melatonin levels and CSHQ, as well as melatonin levels and SCORAD, although there was a strong and significant correlation between SCORAD and CSHQ. Therefore, melatonin levels may not be the main cause of sleep disturbances in children with moderate AD.

Successful Treatment of Non-Langerhans Cell Histiocytosis With Topical Rapamycin in Two Pediatric Cases.

Non-Langerhans cell histiocytosis (non-LCH) is a group of diseases characterized by the proliferation of histiocytes in tissues that is excluded from the diagnostic criteria for LCH. Juvenile xanthogranuloma (JXG) and benign cephalic histiocytosis (BCH) are the most common types of cutaneous non-LCH. These two diseases share similarities in both clinical and histological features, therefore, they can be difficult to differentiate. Thorough physical, dermoscopic, and histopathological examinations are required to distinguish between JXG and BCH. We hereby present two rare cases of non-LCH in pediatric patients, presented with JXG and BCH. The dermoscopic examination of both cases showed a setting-sun appearance, while the histopathological examination revealed Touton giant cells in the JXG case, and massive lymphocyte infiltration in the BCH case. Both patients were treated with 1% topical rapamycin in a split-side comparison for the first 12 weeks, followed by applications on both sides for a total duration of 24 weeks. As a result, there was a significant reduction in the size of the lesion, leading to patient's satisfaction. Rapamycin is an immunosuppressive agent with antineoplastic activity. Rapamycin can be used as an alternative non-invasive topical treatment option for JXG and BCH. However, long-term observations are required to assess its effectiveness and side effects.

Extensive Type V Aplasia Cutis Congenita Without Fetus Papyraceus or Placental Infarction: A Rare Case.

Aplasia cutis congenita (ACC) is a congenital disorder characterized by the absence of epidermis, dermis, and sometimes subcutaneous tissue and bone. There are nine types of ACC based on the number and location of the lesions as well as the presence or absence of associated deformities, with type I ACC being the most common. Type V affects the trunk with a characteristic pattern resembling the "H" letter of the alphabet, generally accompanied by fetus papyraceus (death of one of the twin fetuses) or placental infarction. Type V ACC without fetus papyraceus and placental infarction is a rare case. We reported a case of type V ACC in a 3-day-old baby girl, with clinical manifestation of extensive ulcers on the scalp, back, buttocks, and both lower extremities, in an "H"-shaped pattern, with history of placenta accreta, but no fetus papyraceus or placental infarction was found. The patient received dialkyl carbamoyl chloride hydrophobic swab with hydrogel (Sorbact® gel dressing-BSN Medical) and hydrocolloid wound dressing with good response, as indicated by the wounds becoming dried up, leaving an atrophic scar. Complete epithelialization was achieved in 72 days. The cause of type V ACC remains not completely understood. The diagnosis of ACC can be established based on clinical manifestations. Further examination is required if extracutaneous involvement is suspected. Early identification of the etiology of the lesions and appropriate investigation and treatment, including conservative wound management, are needed so that aplastic lesions can heal successfully, although cosmetic repair may be required at a later stage.

Schimmelpenning Syndrome with Large Nevus Sebaceous and Multiple Epidermal Nevi.

Epidermal nevus syndromes are a group of rare multiorgan disorders. Schimmelpenning syndrome is a clinical variant of epidermal nevus syndromes. This congenital syndrome is characterized by the existence of nevus sebaceous and usually accompanied by abnormalities of the eyes, skeletal, cardiovascular, and central nervous systems. A 2-year-old girl presented with large, hairless, yellowish-brown plaques on the scalp and face along with multiple brownish-black verrucose plaques and brownish-black macules on almost all parts of the body. The skin-colored verrucose tumors were also found on the lips and around the mouth. Histopathological examination of the lesion on the forehead revealed hyperkeratosis, acanthosis, and sebaceous gland hyperplasia supporting the diagnosis of nevus sebaceous, while histopathological examination of the lesions on the lips and abdomen demonstrated hyperkeratosis, acanthosis, and papillomatosis consistent with verrucous epidermal nevus. The pediatrician suspected that the patient had mental retardation; however, there were no neurological, cardiac, skeletal, nor ophthalmologic abnormalities. The lesions on the lips and around the mouth were excised, and it demonstrated a good result. To conclude, epidermal nevus syndrome (e.g., Schimmelpenning syndrome) should be considered in children born with nevus sebaceous.

Monomeric IgE and lipopolysaccharide synergistically prevent mast-cell apoptosis.

The apoptosis of bone marrow-derived mast-cells (BMMCs) after growth factor withdrawal was significantly prevented by a high concentration of IgE in the absence of antigen, and further enhanced by the presence of Toll-like receptor4 (TLR4) ligand, lipopolysaccharide (LPS). The effect of LPS was mediated by TLR4, since TLR4-deficient BMMCs did not show synergistic effects with IgE. The neutralizing amount of anti-IL-3 did not reverse the anti-apoptotic effects of both IgE and combination with LPS. LPS treatment with monomeric IgE synergistically prevented the loss of mitochondrial membrane potentials and was associated with an enhanced expression of anti-apoptotic protein, Bcl-xL, or with a reduced expression of proapoptotic protein, Puma, and Bim, respectively. Altogether, these results suggest that LPS, in a TLR4-dependent manner, together with IgE, synergistically prevent mast-cell apoptosis and may contribute to regulate the tissue mast-cell number.

The extra domain A of fibronectin stimulates murine mast cells via toll-like receptor 4.

The activation of mast cells by extra domain A of fibronectin (FN-EDA), an endogenous ligand of TLR4, and its contribution to the pathogenesis of rheumatoid arthritis (RA) in vivo were examined. FN-EDA, but no other domain of the fibronectin fragment, III(11) (FN-III(11)) and III(12) (FN-III(12)), stimulated bone marrow-derived murine mast cells (BMMCs) dose-dependently to secret cytokines (TNF-alpha, IL-6, and IL-1beta), similar to the pattern produced by LPS. FN-EDA-induced cytokine production was mediated by TLR4, as cytokine production by FN-EDA was absent in TLR4-deficient (TLR4-/-) BMMCs. We examined the roles of TLR4-mediated mast cell activation by this form of fibronectin fragment in the pathogenesis of RA in vivo. The injection of FN-EDA, but not FN-III(11)and FN-III(12), to joints resulted in joint swelling of mice in vivo. Genetically mast cell-deficient WBB6F(1)-W/W(v) mice exhibited significantly less swelling and cytokine production compared with mast cell-sufficient +/+ mice, suggesting that swelling and inflammatory cytokine production were partially dependent on tissue mast cells. Reduced swelling and cytokine production were recovered by the reconstitution of tissue mast cells by the injection of BMMCs from wild-type mice but not from TLR4-/- mice. Altogether, these results suggest that the TLR4-mediated activation of mast cells by endogenous ligand FN-EDA might contribute to the pathogenesis of RA through proinflammatory cytokine production.

A clinician's reference guide for the management of atopic dermatitis in Asians.

BACKGROUND: Atopic dermatitis (AD) is a common skin condition among Asians. Recent studies have shown that Asian AD has a unique clinical and immunologic phenotype compared with European/American AD. OBJECTIVE: The Asian Academy of Dermatology and Venereology Expert Panel on Atopic Dermatitis developed this reference guide to provide a holistic and evidence-based approach in managing AD among Asians. METHODS: Electronic searches were performed to retrieve relevant systematic reviews and guidelines on AD. Recommendations were appraised for level of evidence and strength of recommendation based on the U.K. National Institute for Health and Care Excellence and Scottish Intercollegiate Guidelines Network guidelines. These practice points were based on the consensus recommendations discussed during the Asia Pacific Meeting of Experts in Dermatology held in Bali, Indonesia in October 2016 and April 2017. RESULTS: The Expert Panel recommends an approach to treatment based on disease severity. The use of moisturizers is recommended across all levels of AD severity, while topical steroids are recommended only for flares not controlled by conventional skin care and moisturizers. Causes of waning efficacy must be explored before using topical corticosteroids of higher potency. Topical calcineurin inhibitors are recommended for patients who have become recalcitrant to steroid, in chronic uninterrupted use, and when there is steroid atrophy, or when there is a need to treat sensitive areas and pediatric patients. Systemic steroids have a limited role in AD treatment and should be avoided if possible. Educational programs that allow a patient-centered approach in AD management are recommended as an adjunct to conventional therapies. Recommendations on the use of phototherapy, systemic drugs, and emerging treatments are also included. CONCLUSION: The management of AD among Asians requires a holistic approach, integrating evidence-based treatments while considering accessibility and cultural acceptability.