Efficacy and Safety Profile of Tuberculin Protein Purified Derivative Injection As Immunotherapy For the Treatment of Cutaneous and Anogenital Warts: A Review Article.

Introduction: Various treatments available today for anogenital and cutaneous warts have limitations, including time-consuming, challenging to perform, and the risk of scarring. A new treatment using tuberculin purified protein derivative (PPD) has been developed, which is expected to generate cellular immunity against HPV. Objective: To assess the evidence for the efficacy and safety of PPD treatment for cutaneous and anogenital warts. Materials and methods: A literature search was performed with the keyword-based search on digital libraries, including the National Library of Medicine, Cochrane Controlled Register of Trial, and Google Scholar, using the following terms: anogenital warts, condyloma acuminata, cutaneous warts, human papillomavirus, immunotherapy, and tuberculin purified protein derivative. Original studies on treating cutaneous or anogenital warts with PPD were included. The results were 47 clinical trials and 4 case reports. Most of the research was done in countries with common Mycobacterium tuberculosis infection. The treatment showed good efficacy. Comparative studies showed that the treatment has similar efficacy with other immunotherapies. No significant side effects were reported, with evidence of the safety use on the pregnant population. Conclusion: Based on good efficacy and safety, PPD can be considered an alternative therapy, especially in countries where tuberculosis is frequent.

Elephantiasis Nostras Verrucosa: A Treated Case With Dietary Intervention and Acitretin.

Elephantiasis nostras verrucosa (ENV) is a rare and extreme complication of chronic non-filarial lymphedema. It can lead to severe disfiguration of body parts, especially the lower extremities, and is characterized by non-pitting edema and papulonodules with a verrucose or cobblestone-like appearance. Obesity is a risk factor of ENV. Various treatments have been reported for ENV. A 52-year-old woman presented to our outpatient dermatology clinic with non-pitting edema, cobblestone-like papulonodules, and erythematous plaques on both legs for 2 years. Her medical history included morbid obesity with a body mass index of 44.8 kg/m2, hypertension, and type II diabetes mellitus. Biopsy specimens obtained from skin lesions showed multiple dilated lymph nodes throughout the papillary and reticular dermis. Doppler ultrasonography and lymphoscintigraphy revealed lymph stasis and lymphedema, respectively. Based on clinical, histopathological, and imaging findings, the final diagnosis was ENV. She was initially treated with conservative approaches such as compression stockings and dietary intervention for a month. She went on a low-calorie diet (1350 kcal/day) consisting protein 50.7 g/day, fat 32.5 g/day, and carbohydrate 202.7 g/day, for a month. Owing to the hyperkeratotic lesions, she was given oral acitretin 0.3 mg/kg/day. The dosage was increased to 0.6 mg/kg/day after one month. The lesions were slightly flattened after 2 months of therapy. Acitretin was ceased. Early identification is crucial for preventing morbidity in patients with ENV. Management of ENV is challenging for physicians because of the lack of definitive treatment and poor prognosis. In the management of ENV, it is crucial to treat underlying causes, such as obesity. Acitretin induces loosening and thinning of the hyperkeratotic stratum corneum. Thus, it can result in improvement of cutaneous ENV lesions.

A Rare Case on Capecitabine Induced Acquired Palmoplantar Keratoderma.

Acquired palmoplantar keratoderma (PPK) is a non-hereditary hyperkeratosis of the palms and soles that is caused by various factors, including chemotherapeutic agents. The purpose of this case report is to present a rare case of acquired PPK caused by the chemotherapeutic agent capecitabine. A 54-year-old female complained of painful erythematous plaques on her palms and soles with history of consuming capecitabine. Physical examination revealed scaly erythematous plaques on the palmoplantar surface and knuckle pads on both hands. Histopathological features showed hyperkeratosis, acanthosis, vasodilatation, and perivascular lymphocytic infiltration. Therefore, the patient was diagnosed with acquired PPK due to capecitabine. The dose of capecitabine was reduced and the patient was administered topical corticosteroid and emollient. Improvement of skin lesions was strongly observed after discontinuation of capecitabine. The underlying cause of PPK should be identified to determine the appropriate treatment. Dose reduction or drug discontinuation is the mainstay therapy for patients with acquired PPK caused by chemotherapeutic agents.

Characteristics of Xerosis, Pruritus, and Pallor in Stage 5 Chronic Kidney Disease Patients Undergoing Hemodialysis at Dr. Hasan Sadikin General Hospital, Bandung.

Purpose: This study aims to delineate the demographic and clinical characteristics of xerosis, pruritus, and pallor among patients with stage 5 chronic kidney disease (CKD) undergoing hemodialysis at Dr. Hasan Sadikin General Hospital, Bandung. Patients and Methods: This cross-sectional, descriptive study involved the analysis of 139 selected medical records of patients with stage 5 CKD who underwent hemodialysis between July and August 2022. A comprehensive examination was conducted by a dermatovenereologist, and the findings were duly recorded in the patients' medical records. The documentation encompassed gender, age, employment status, as well as the clinical characteristics of xerosis, pruritus, and pallor. The collected data were analyzed using descriptive statistical methods. Results: Out of the 139 patients, 70 (50.4%) were male, while 69 (49.6%) were female. The mean (SD) age was 47.6 (11.8) years. The majority of the patients were unemployed (n=96, 69.1%). The median (IQR) duration of hemodialysis was 48 (96.0-24.0) months. The predominant findings were xerosis (n=84, 60.4%) and pallor (n=83, 59.7%), followed by pruritus (n=56, 40.3%). Instances of xerosis were more frequently observed in males, whereas pallor was more prevalent in females. Xerosis and pruritus exhibited higher prevalence in the ≥65 years age group, whereas pallor was more common in the 18-44 years age group. In contrast to xerosis, pruritus and pallor were more frequently noted in the unemployed group. Xerosis was predominantly mild with overall dry skin (ODS) score of one, and it was mainly observed on the patients' legs. Among those experiencing pruritus, over half displayed a moderate severity with visual analogue scale (VAS) scores ranging from ≥3 to <7. Patients with pallor mostly exhibited hemoglobin levels below 10 g/dL. Conclusion: Xerosis, pruritus, and pallor were prevalent among patients with stage 5 CKD undergoing hemodialysis. These disorders presented with distinct demographic and clinical characteristics. Timely diagnosis and intervention have the potential to enhance the quality of life for these patients.

Successful Therapy of Alopecia Universalis Using a Combination of Systemic Methotrexate and Corticosteroids and Topical 5% Minoxidil.

Alopecia areata (AA) is an autoimmune disease-specific to specific organs mediated by T lymphocytes with hair follicles as targets. Severe AA could be in the form of alopecia universalis (AU). AU therapy is relatively difficult and challenging with varying outcomes. Herein, we reported a case of AU in a 19-year-old man with alopecia in the hairy scalp area, eyebrows, eyelashes, moustache, beard, and axillary hair since 2.5 years ago. The patient's severity of alopecia tool (SALT) score was 100%. The patient was given a combination therapy of 15 mg methotrexate per week and 16 mg methylprednisolone per day orally and topical treatment with minoxidil 5%. Observations after nine months of treatment showed an improvement in the decrease in SALT scores to 41%. However, striae were found after 3rd month of therapy. Systemic combination therapy of methotrexate and low-dose corticosteroids and topical minoxidil 5% in this patient gave responsive results. Performed the hematological examination, liver function levels, blood glucose levels, and cortisol during long-term use of methotrexate and corticosteroids are necessary. The combination of systemic methotrexate and corticosteroids, and topical minoxidil showed promising results in AU. Nevertheless, long-term observation is still needed to monitor the side effects of therapy.

A Pilot Study: Composition and Diversity of 16S rRNA Based Skin Bacterial Microbiome in Indonesian Atopic Dermatitis Population.

BACKGROUND: Atopic dermatitis (AD) interferes with quality of life and is influenced by important factors like skin microbiome. The results of the skin microbiome composition and diversity in AD varied in some studies. PURPOSE: This study aims to determine the composition and diversity of the skin microbiome in Indonesian AD patients. PATIENTS AND METHODS: Genomic deoxyribonucleic acid (DNA) preparations were obtained from skin swabs of the cubital fossa of 16 subjects, nine of which were having mild AD, three moderate AD, and four healthy individuals. DNA extraction and sequencing of the 16S ribosomal ribonucleic acid (rRNA) gene using next-generation sequencing and bioinformatics analysis were further performed. RESULTS: Firmicutes (p), Bacilli (c), Bacillales (o), Staphylococcaceae (f), and Staphylococcus (g) were dominant in moderate AD. On the contrary, Proteobacteria (p), Gammaproteobacteria (c), Pseudomonadales (o), Moraxellaceae (f), and Acinetobacter (g) were dominant in mild AD. Staphylococcus aureus was found in the highest number in individuals with moderate AD. Interestingly, Ensifer adhaerens was found in mild AD. Microbial diversity was decreased in moderate AD. CONCLUSION: Metagenomic analysis in this study identified microbes in moderate and mild AD and showed a low diversity of skin microbiomes in moderate AD. Interestingly, this is the first time that the bacteria Ensifer adhaerens was detected on the human skin.

SNAP23 deficiency causes severe brain dysplasia through the loss of radial glial cell polarity.

In the developing brain, the polarity of neural progenitor cells, termed radial glial cells (RGCs), is important for neurogenesis. Intercellular adhesions, termed apical junctional complexes (AJCs), at the apical surface between RGCs are necessary for cell polarization. However, the mechanism by which AJCs are established remains unclear. Here, we show that a SNARE complex composed of SNAP23, VAMP8, and Syntaxin1B has crucial roles in AJC formation and RGC polarization. Central nervous system (CNS)-specific ablation of SNAP23 (NcKO) results in mice with severe hypoplasia of the neocortex and no hippocampus or cerebellum. In the developing NcKO brain, RGCs lose their polarity following the disruption of AJCs and exhibit reduced proliferation, increased differentiation, and increased apoptosis. SNAP23 and its partner SNAREs, VAMP8 and Syntaxin1B, are important for the localization of an AJC protein, N-cadherin, to the apical plasma membrane of RGCs. Altogether, SNARE-mediated localization of N-cadherin is essential for AJC formation and RGC polarization during brain development.

A Case Series: Experience of Using 20% Potassium Hydroxide Solution to Treat Adult Sexually Transmitted Molluscum Contagiosum.

BACKGROUND: Molluscum contagiosum (MC) is a benign disease of the skin and mucous membrane caused by a poxvirus. To date, there is no standard therapy used for the treatment of MC. Using 10% of potassium hydroxide (KOH) once or twice a day and 20% KOH once a day are often applicable to MC lesions both in children and adults. Nevertheless, the usage of 20% KOH twice a day still has not been reported. PURPOSE: This case series aimed to show the efficacy and side effects of once- or twice-daily application of 20% KOH solution for MC lesions due to sexually transmitted infections (STIs) in adults. PATIENTS AND METHODS: Three cases of MC on the genital were applied once or twice daily and one case of MC on the face was applied twice daily using 20% KOH solution. RESULTS: As a result, the application of 20% KOH twice daily showed the improvement of MC lesions on the face on day 7 and MC lesions on the genital on day 20. Meanwhile, once-daily application of 20% KOH showed diminished MC lesions on genital on day 25-31 after treatment. There were tolerable side effects that occurred in this treatment, such as stinging and burning sensation several minutes after application, erosions, and post-inflammatory hypo- and hyper-pigmentation. CONCLUSION: The 20% KOH solution twice daily on MC lesions in adults is effective, practical, and inexpensive.

A unique case of borderline lepromatous leprosy with psoriasis-like lesions all over the body and mycosis fungoides-like lesions on the face.

Clinical manifestations of leprosy are various and may resemble other skin diseases. Skin lesions of leprosy mimicking psoriasis and mycosis fungoides (MF) that simultaneously occurs in one patient are rare. We reported a unique case of borderline lepromatous (BL) leprosy with severe reversal reaction manifested as psoriasis-like lesions and MF-like lesions in a 43-year-old-man. Psoriasis-like lesions all over the body accompanied by plaques and tumor-like lesions mimicking MF on the face could be found in this patient. Histopathological examination on an MF-like lesion from the face and psoriasis-like lesions from the posterior trunk and lower extremities revealed granulomatous reaction with epithelioid cells, Langhans giant cells, and foam cells which supported the diagnosis of BL leprosy. The patient was treated with multidrug therapy multibacillary (MDT-MB) regimen and 40 mg prednisone daily which was tapered off. Clinical improvement was observed on the 32nd day of observation as psoriasis-like and MF-like lesions became hyperpigmented macules and plaques, respectively. Due to the rarity of the multitype skin lesions of leprosy in one patient, a diagnosis of leprosy should be suspected by the clinicians in any patients with previously described skin disorders, especially in an endemic area.

Clinical pilot study: Clarithromycin efficacy in multibacillary leprosy therapy.

Background: Rifampicin is one of the important components in the multidrug therapy (MDT)-World Health Organization regimen for leprosy. Clarithromycin is one of the alternative therapies of rifampicin. Methods: This clinical pilot study was to compare the efficacy of 2,000 mg clarithromycin to 600 mg rifampicin in combination with dapsone and clofazimine for 3 months in multibacillary (MB) leprosy patients. They were divided into an MDT-MB regimen group that consists of rifampicin-dapsone-clofazimine and clarithromycin-dapsone-clofazimine (CDC) regimen group, each group consisted of seven patients. Results: The morphological index (MI) was reduced insignificantly after 3 months therapy in MDT-MB group (P = 0.248). While in the CDC group, the MI decrement showed a significant result (P = 0.004). The comparison of MI reduction in MDT-MB and CDC groups showed an insignificant difference (P = 0.130). Skin discoloration was occurred in both groups, whereas mild-nausea was presented in the CDC group, in addition, red-colored urine was developed in the MDT-MB group. Conclusion: We concluded that 2,000 mg clarithromycin is as effective as 600 mg rifampicin in combination with dapsone and clofazimine regimen in MB leprosy patients. Hence, clarithromycin can be considered as an alternative therapy for leprosy patients who resistance and/or allergy to rifampicin.

BIG1 is required for the survival of deep layer neurons, neuronal polarity, and the formation of axonal tracts between the thalamus and neocortex in developing brain.

BIG1, an activator protein of the small GTPase, Arf, and encoded by the Arfgef1 gene, is one of candidate genes for epileptic encephalopathy. To know the involvement of BIG1 in epileptic encephalopathy, we analyzed BIG1-deficient mice and found that BIG1 regulates neurite outgrowth and brain development in vitro and in vivo. The loss of BIG1 decreased the size of the neocortex and hippocampus. In BIG1-deficient mice, the neuronal progenitor cells (NPCs) and the interneurons were unaffected. However, Tbr1+ and Ctip2+ deep layer (DL) neurons showed spatial-temporal dependent apoptosis. This apoptosis gradually progressed from the piriform cortex (PIR), peaked in the neocortex, and then progressed into the hippocampus from embryonic day 13.5 (E13.5) to E17.5. The upper layer (UL) and DL order in the neocortex was maintained in BIG1-deficient mice, but the excitatory neurons tended to accumulate before their destination layers. Further pulse-chase migration assay showed that the migration defect was non-cell autonomous and secondary to the progression of apoptosis into the BIG1-deficient neocortex after E15.5. In BIG1-deficient mice, we observed an ectopic projection of corticothalamic axons from the primary somatosensory cortex (S1) into the dorsal lateral geniculate nucleus (dLGN). The thalamocortical axons were unable to cross the diencephalon-telencephalon boundary (DTB). In vitro, BIG1-deficient neurons showed a delay in neuronal polarization. BIG1-deficient neurons were also hypersensitive to low dose glutamate (5 µM), and died via apoptosis. This study showed the role of BIG1 in the survival of DL neurons in developing embryonic brain and in the generation of neuronal polarity.

Interleukin-18 correlates with interleukin-4 but not interferon-γ production in lymphocyte cultures from atopic dermatitis patients after staphylococcal enterotoxin B stimulation.

BACKGROUND: Staphylococcus aureus (S. aureus) triggers exacerbation of atopic dermatitis (AD) and causes chronic inflammation through the action of various proteins such as staphylococcal enterotoxin B (SEB). SEB has a role in activating interleukin (IL)-18, an important regulator of interferon (IFN)-γ and IL-4, in regards to a therapeutic strategy. OBJECTIVE: To determine the correlation of IL-18 level with the IL-4 and IFN-γ level in lymphocyte cultures from AD patients following SEB stimulation. METHOD: Twenty patients with AD based on the Hanifin and Rajka criteria and 20 healthy subjects as a control group were selected. A 5 ml blood sample from each subject was taken for lymphocyte culture. The culture was stimulated with SEB for two days and the outcomes were assessed by enzyme-linked immunosorbent assays (ELISA) to evaluate the levels of IL-18, IL-4, and IFN-γ. RESULTS: In the AD group, the levels of IL-18, IL-4, and IFN-γ in lymphocyte cultures with SEB were significantly increased compared with non-SEB exposed cells (each p<0.001); similar results were found in the control group. The level of IL-18 was significantly elevated in lymphocyte cultures with SEB stimulation in AD vs. control (p<0.05) and without SEB in AD vs. control (p<0.05). Furthermore, IL-18 levels were significantly correlated with IL-4 levels and score atopic dermatitis (SCORAD) values in AD patients with SEB (r=0.41, p<0.05; and r=0.70, p<0.05, respectively); on the in contrary, there was no correlation between IL-18 and IFN-γ levels (p=0.469). CONCLUSIONS: Our results suggest that IL-18 is correlated with increased of IL-4 levels in SEB-stimulated AD lymphocyte cultures.

Functional redundancy of protein kinase D1 and protein kinase D2 in neuronal polarity.

Mammalian protein kinase D (PKD) isoforms have been proposed to regulate diverse biological processes, including the establishment and maintenance of neuronal polarity. To investigate the function of PKD in neuronal polarization in vivo, we generated PKD knockout (KO) mice. Here, we show that the brain, particularly the hippocampus, of both PKD1 KO and PKD2 KO mice was similar to that of control animals. Neurite length in cultured PKD1 KO and PKD2 KO hippocampal neurons was similar to that of wild-type neurons. However, hippocampal neurons deficient in both PKD1 and PKD2 genes showed a reduction in axonal elongation and an increase in the percentage of neurons with multiple axons relative to control neurons. These results reveal that whereas PKD1 and PKD2 are essential for neuronal polarity, there exists a functional redundancy between the two proteins.

The role of PKD in cell polarity, biosynthetic pathways, and organelle/F-actin distribution.

Protein Kinase D (PKD) 1, 2, and 3 are members of the PKD family. PKDs influence many cellular processes, including cell polarity, structure of the Golgi, polarized transport from the Golgi to the basolateral plasma membrane, and actin polymerization. However, the role of the PKD family in cell polarity has not yet been elucidated in vivo. Here, we show that KO mice displayed similar localization of the apical and basolateral proteins, transport of VSV-G and a GPI-anchored protein, and similar localization of actin filaments. As DKO mice were embryonic lethal, we generated MEFs that lacked all PKD isoforms from the PKD1 and PKD2 double floxed mice using Cre recombinase and PKD3 siRNA. We observed a similar localization of various organelles, a similar time course in the transport of VSV-G and a GPI-anchored protein, and a similar distribution of F-actin in the PKD-null MEFs. Collectively, our results demonstrate that the complete deletion of PKDs does not affect the transport of VSV-G or a GPI-anchored protein, and the distribution of F-actin. However, simultaneous deletion of PKD1 and PKD2 affect embryonic development, demonstrating their functional redundancy during development.