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.

Characteristics of Biofilm-Forming Ability and Antibiotic Resistance of Cutibacterium acnes and Staphylococcus epidermidis from Acne Vulgaris Patients.

Introduction: Acne vulgaris (AV) is a common and chronic disorder of the pilosebaceous unit and has a multifactorial pathology, including activities of Cutibacterium acnes (C. acnes) and Staphylococcus epidermidis (S. epidermidis). Antibiotic resistance has become a major concern in dermatology daily practice, and the ability of biofilm formation by both bacteria is suggested to increase antibiotic resistance in acne. Purpose: Our aim was to analyze the comparison of antibiotic resistance between biofilm-forming (BF) and non-biofilm-forming (NBF) strains of C. acnes and S. epidermidis towards seven antibiotics commonly used for acne. Methods: This is a cross-sectional analytical study involving 60 patients with AV. Samples were obtained from closed comedones on the forehead using the standardized skin surface biopsy (SSSB) method at the Cosmetic Dermatology Clinic Dr. Hasan Sadikin in Bandung, Indonesia. Isolates were cultured and identified before undergoing the biofilm-forming test using the tissue culture plate method. Antibiotic susceptibility testing for each antibiotic was then performed using the disc diffusion method. Results: The incidence of antibiotic resistance to clindamycin in BF and NBF C. acnes isolates was 54.5% (p=1.00), while in BF and NBF S. epidermidis isolates, it was 54.5% and 45.5% respectively (p=0.67). The incidence of antibiotic resistance to erythromycin and azithromycin in BF and NBF C. acnes isolates was 54.5% and 63.6% respectively (p=1.00), whereas for S. epidermidis BF and NBF isolates, it was 54.5% (p=1.00). There was no resistance observed to tetracycline, doxycycline, levofloxacin, and cotrimoxazole in all groups. Conclusion: There were no significant differences in resistance against seven antibiotics between the C. acnes and S. epidermidis in BF and NBF groups. Furthermore, although statistically not significant, some resistances were observed against clindamycin, erythromycin, and azithromycin. Consequently, the use of these three antibiotics should be judiciously regulated.

Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial.

Wound healing in DFU (diabetic foot ulcer) has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream in enhancing wound healing rate and decreasing the levels of IL-1α, TNF-α, and the number of aerobic bacteria colonization in DFU with mild infection. This study was conducted from January 2020 to June 2021 in Jakarta. Subjects were instructed to apply either LL-37 cream or placebo cream twice a week for 4 weeks. Wounds were measured on days 7, 14, 21, and 28 and processed with ImageJ. The levels of LL-37, IL-1α, and TNF-α from wound fluid were measured using ELISA. The number of aerobic bacteria colonization was counted from the isolate grown in culture. The levels of LL-37 in DFU at baseline were equally low in both groups which were 1.07 (0.37-4.96) ng/mg protein in the LL-37 group and 1.11 (0.24-2.09) ng/mg protein in the placebo group. The increase in granulation index was consistently greater in the LL-37 group on days 7, 14, 21, and 28 (p = 0.031, 0.009, 0.006, and 0.037, respectively). The levels of IL-1α and TNF-α increased in both groups on days 14 and 21 (p > 0.05). The decrease in the number of aerobic bacteria colonization was greater in the LL-37 group on days 7, 14 and 21, but greater in the placebo group on day 28 (p > 0.05). In conclusion, LL-37 cream enhanced the healing rate of DFU with mild infection, but did not decrease the levels of IL-1α and TNF-α and the number of aerobic bacteria colonization. This trial is registered at ClinicalTrials.gov, number NCT04098562.

Successful treatment of anogenital warts with single dose Bacillus Calmette Guerin vaccine without prior sensitization in tuberculosis endemic country: Two case report.

Anogenital Warts (AGWs) are benign proliferations caused by Human Papillomavirus (HPV) infection on the genital or anal areas. Various therapeutic options are available for the treatment of AGWs but there is no best or ideal therapy, and the recurrence of AGWs is significantly high. A promising new therapy that is currently being evaluated is immunotherapy with the intralesional Bacillus Calmette-Guérin (BCG) vaccine. Two cases of a 23-year-old woman and a 41-year-old man were presented with manifestations of condyloma acuminata type AGWs. The patients were immunocompetent and received single dose intralesional BCG vaccine on the largest lesion. Clinical improvements of AGWs lesions were noted starting on the 14th day after receiving therapy by the disappearance of some lesions with no recurrence and side effects. Intralesional BCG vaccine activates the immune system, treats other AGWs lesions that do not receive an intralesional injection, and also prevents recurrence. Although the intralesional BCG vaccine is effective for treating AGWs, further evaluation is still needed for its recurrence.

The Chemoprotective Role of Vitamin D in Skin Cancer: A Systematic Review.

Introduction: Research in mice showed that vitamin D receptor deficiency was correlated with an increased rate of non-melanoma skin cancer. Therapeutic supplemental vitamin D has also been reported to reduce cell growth in both melanoma and non-melanoma skin cancer. This paper aims to describe the existing research studies that discuss the potential and role of vitamin D in the management of skin cancer. Methods: Articles were searched from three databases (PubMed, ScienceDirect, Scopus) and manual search. 18 articles were included. These were further divided into in vivo and in vitro studies. The literature search was based on the following Patients, Intervention, Control, and Outcome (PICO) criteria: Patients with any types of skin cancer; Vitamin D and their derivates as the intervention; placebo or standard regimen as control, and survival rate or response rate as primary outcome. Results: From the three databases, we obtained 802 studies. Prior to screening of the literature obtained, several studies were excluded. In the eligibility assessment, seven studies were excluded due to their outcomes being not eligible for analysis, and two studies were excluded due to inaccessible full texts. The remaining 18 studies were included. Five studies had a clinical research design (randomized controlled trial or interventional study), which use vitamin D3 as vitamin D derivatives and the results showed that the administration of vitamin D3 reduces the proliferation of skin cancer cells. Similar results were also reported in studies with pre-clinical research designs, either in vivo or in vitro, where six were in vivo studies and nine studies were in vitro studies. Conclusion: Our literature review revealed that that vitamin D derivatives, such as 1,25(OH)2D3 or 20(OH)D3 can effectively reduce the proliferation of skin cancer cells by contributing in the inhibition of cell growth and development, highlighting vitamin D's role as good prognostic factor.

Akkermansia muciniphila and Faecalibacterium prausnitzii in Immune-Related Diseases.

Probiotics and synbiotics are used to treat chronic illnesses due to their roles in immune system modulation and anti-inflammatory response. They have been shown to reduce inflammation in a number of immune-related disorders, including systemic lupus erythematosus (SLE), human immunodeficiency virus (HIV), and chronic inflammatory skin conditions such as psoriasis and atopic dermatitis (AD). Akkermansia muciniphila (A. muciniphila) and Faecalibacterium prausnitzii (F. prausnitzii) are two different types of bacteria that play a significant part in this function. It has been established that Akkermansia and Faecalibacterium are abundant in normal populations and have protective benefits on digestive health while also enhancing the immune system, metabolism, and gut barrier of the host. They have the potential to be a therapeutic target in diseases connected to the microbiota, such as immunological disorders and cancer immunotherapy. There has not been a review of the anti-inflammatory effects of Akkermansia and Faecalibacterium, particularly in immunological diseases. In this review, we highlight the most recent scientific findings regarding A. muciniphila and F. prausnitzii as two significant gut microbiota for microbiome alterations and seek to provide cutting-edge insight in terms of microbiome-targeted therapies as promising preventive and therapeutic tools in immune-related diseases and cancer immunotherapy.

Multiple Bullous and Ulcers as Cutaneous Manifestations of Wegener's Granulomatosis: A Rare Case Report.

Bullous dermatoses is a heterogeneous group of blistering skin disorders that can either be inherited or acquired. Subepidermal blisters may result in ulceration and scarring following their rupture. Wegener's granulomatosis (WG) is a granulomatous necrotizing vasculitis affecting small- to medium-sized blood vessels. It is associated with anti-neutrophil cytoplasmic antibodies (ANCA) and can be manifested cutaneously as multiple bullous and ulcers. A case of WG was reported in an 18-year-old man presented with multiple skin bullous and ulcers. The patient was diagnosed with WG based on the findings from nasopharyngoscopy examination that revealed crusts in his nasal cavity; necrotizing granulomatous appearance on chest radiograph; hematuria on urinalysis; and positive ANCA blood test. This patient received a combination of methylprednisolone and methotrexate, resulting in improvement within four weeks of therapy. His multiple skin ulcers were treated with a combination of dialkyl carbamoyl chloride, hydrocolloid, and hydrogel dressings. This patient was in complete remission state after six months of treatment, which later followed by a relapse episode that occurred within one year. WG with multiple skin bullous and ulcers can mimic other diseases. Various examinations such as histopathology, direct immunofluorescence, and ANCA blood test may aid in determining the etiology of skin bullous and ulcers.

Calcitriol Inhibits Proliferation and Potentially Induces Apoptosis in B16-F10 Cells.

BACKGROUND Melanoma is one of the most aggressive types of cancer and it has shown a remarkable surge in incidence during the last 50 years. Melanoma has been projected to be continuously rising in the future. Therapy for advanced-type melanoma is still a challenge due to the low response rate and poor 10-year survival. Interestingly, several epidemiological and preclinical studies had reported that vitamin D deficiency was associated with disease progression in several cancer types. In vivo and in vitro studies revealed anti-proliferative, anti-angiogenic, apoptosis, and differentiation induction effects of calcitriol in various cancers. However, information on the effects of calcitriol (1,25(OH)2D3) on melanoma is still limited, and its mechanism remains unclear. MATERIAL AND METHODS In the present study, by utilizing B16-F10 cells, which is a melanoma cell line, we explored the anti-proliferative effect of calcitriol using cell viability assay, near-infrared imaging, expression of apoptosis-related genes using real-time polymerase chain reactions (PCR), and the expression of apoptosis proteins levels using western blot. In addition, we also assessed calcitriol uptake by B16-F10 cells using high-performance liquid chromatography (HPLC). RESULTS We found that calcitriol inhibits melanoma cell proliferation with an IC50 of 93.88 ppm (0.24 µM), as shown by cell viability assay. Additionally, we showed that B16-F10 cells are capable of calcitriol uptake, with a peak uptake time at 60 min after administration. Calcitriol was also able to induce apoptosis-related proteins such as caspase-3, caspase 8, and caspase-9. These effects of calcitriol reflect its potential utility as a potent adjuvant therapy for melanoma. CONCLUSIONS Calcitriol inhibits cell proliferation and induces apoptosis in B16-F10 cells.

Success of Intralesional Purified Protein Derivative Immunotherapy in the Treatment of Anogenital Warts: A Case Report.

Anogenital warts (AGW) are among the most common sexually transmitted infections worldwide. The condition may be persistent, increase in size and number, and have a high recurrence rate. There are many therapeutic options of AGW, but none of them prevented recurrence, only yielded partial responses and have the propensity to cause scars. Immunotherapy by purified protein derivative (PPD) is one of the therapeutic options for AGW, which effectively reduces the number of lesions until complete clearance, with minimal side effects and less recurrence rate. This case report aims to demonstrate the effectiveness, safety, and low recurrence rate of intralesional PPD injection as an alternative therapy for AGW. We reported one case of AGW in an immunocompetent 30-year-old homosexual man who was given 3 doses of 0.2 mL PPD injected intralesionally. As a result, clinical improvement was observed starting from the 18th day, with some of the lesions decreasing in size, and on the 46th day, all of the lesions disappeared. There was no significant side effect. Within two years of follow-up, no recurrence was observed. Intralesional injection of PPD can stimulate the immune response against human papillomavirus (HPV) infection both on the injection site and distant from the injection site. Previous studies have shown promising results of intralesional PPD, with low recurrence in over six-month follow-up and no side effects. Intralesional injection of PPD can be considered as an alternative therapy due to its minimal side effects and its long-term low recurrence rate.

Erythema Induratum of Bazin Accompanied by Atrophy of the Subcutaneous Fat.

Erythema induratum of Bazin (EIB) is a predominantly lobular panniculitis with or without vasculitis due to Mycobacterium tuberculosis (MTB) infection. Atrophic scars may remain after EIB was healed. Rare cases of EIB showing sharp skin depression may mimic deep morphea and lupus profundus. A rare case of EIB was reported in a 35-year-old female with slightly tender erythematous-violaceous nodules and hyperpigmented depressed scars on both lower legs, resulting in asymmetrical lower leg shape. Histopathological examination showed lobular panniculitis without vasculitis and granulomatous inflammation consisted of caseous necrosis, epithelioid cells, and multinucleated giant cells. Polymerase chain reaction (PCR) from skin biopsy revealed deoxyribonucleic acid (DNA) of MTB. Tuberculin skin test (TST) was positive with a 20-mm induration, and nuclear 99mTc-ethambutol scintigraphy was positive for tuberculosis infection in one-third distal portion of the left lower leg. Clinical improvements were shown after 6 months of antituberculosis therapy. EIB must be considered in patient with erythematous-violaceous nodules on lower leg, especially in endemic areas of tuberculosis infection since diagnosis can be difficult and occasionally, deceptive.

Challenging diagnosis of leprosy in a psychotic homeless patient with atypical clinical manifestations: an interesting case report.

BACKGROUND: A decision to diagnose certain skin diseases in patient undergoing psychotic break is challenging; this includes establishing the diagnosis of leprosy. Diagnosis of leprosy is established if there is at least one of the three cardinal signs of leprosy. Histopathological examination is not a gold standard, but remains useful in atypical or clinically suspicious cases. CASE PRESENTATION: We report for the first time, an interesting case of leprosy with atypical clinical manifestations in a psychotic homeless male with unknown history of present illness. Upon examination, hypopigmented macules, hyperpigmented macules, and plaques were observed, with unclear sensation impairment. Peripheral nerve thickening and acid-fast bacilli from slit-skin smear were not found. Histopathological examination from hypopigmented macule on the upper right limb showed no granulomatous reaction and other histopathological features of leprosy. Although the condition did not fulfill the cardinal signs of leprosy, we found lagophthalmos, claw hands, pseudomutilation of fingers and toes. Therefore, the diagnosis of suspected leprosy was established. The patient was hospitalized and attempts to administer oral rifampicin and clofazimine were made. Several days after treatment, annular erythematous macules appeared on the patient's face, abdomen, and back. Histopathological examination results on sample taken from erythematous macule and right sural nerve were consistent with the diagnosis of leprosy with reversal reaction. CONCLUSION: In certain conditions, histopathological examination of the skin and nerves are a highly rewarding test in establishing a diagnosis of leprosy.

A Successful Defect Closure After Total Excision of Seborrheic Keratoses with Atypical Clinical Presentation Using Island Pedicle Flap in an Elderly Patient.

Seborrheic keratoses (SK) are benign skin tumor characterized by well-demarcated and skin-colored to pigmented papules, plaques, or nodules with stuck-on appearance. Typical SKs are normally treated for cosmetic reasons. However, total excision and histopathological examination have to be considered in SK with unusual properties. The island pedicle flap (IPF) is a method of flap for defect closure, especially on the cheek. It has the capability to maintain the vascularization, thus it is also suitable in the elderly. We report a case of an SK with atypical clinical presentation in a 69-year-old female, with a solitary enlarging, hyperpigmented, verrucous, and bleeding tumor. The dermoscopic examination did not show characteristic features of SK. Total excision was performed due to its clinical properties. The histopathological examination revealed hyperkeratosis, acanthosis, hyperplasia, and papillomatosis, along with intercellular pseudo-horn cyst which confirmed the diagnosis of SK. The patient underwent total excision of the skin lesion which left a primary defect. We performed IPF procedure to reconstruct the defect after total excision of the skin lesion. After a year of follow-up, no meaningful complication was detected. The final result of the procedure was satisfying due to its ability to restore the natural contour and texture match by utilizing cheek laxity, without interfering the nasolabial fold. In conclusion, IPF is an appropriate method for defect closure in an elderly patient after facial total tumor excision.

Frequent testicular involvement in multibacillary leprosy.

OBJECTIVE: Testicular involvement or atrophy in leprosy is silent, unreported, and under-estimated. The aim of this study was to assess the frequency of testicular atrophy and its consequences through the examination of clinical manifestations, hormonal profile, and semen analysis in leprosy patients. METHODS: A descriptive observational study using a cross-sectional design and consecutive sampling method was conducted from May to July 2018. The study was conducted in Dr. Hasan Sadikin General Hospital, Bandung, Indonesia and included 32 men affected by leprosy and five healthy men as a control group. All patients were subjected to history-taking, dermatological and genital examinations, assessment of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone, and testicular ultrasonography examination. Semen analysis was performed for the 10 patients who consented. RESULTS: Testicular atrophy was observed in 93.75% of patients. Clinical manifestations of testicular atrophy were loss of libido (21.87%), female pubic hair pattern (9.38%), gynecomastia (6.25%), and secondary infertility (6.25%). Hormonal imbalance was seen in 16 patients, and all 10 patients who underwent semen analysis showed an abnormality. CONCLUSIONS: This study showed a high frequency of testicular atrophy, but the symptoms were only present in a few of patients. The assessment of testicular function should be recommended as a routine work-up for leprosy patients.

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.

Optimizing ultraviolet B radiation exposure to prevent vitamin D deficiency among pregnant women in the tropical zone: report from cohort study on vitamin D status and its impact during pregnancy in Indonesia.

BACKGROUND: Vitamin D deficiency during pregnancy carries potential threat to fetal well being. Natural conversion of vitamin D in the skin can be facilitated by direct ultra violet B (UVB) radiation, but the effect is reduced by wearing umbrellas, clothes, or sunblock cream. Muslim women wear hijab that allows only face and hands to be seen. With increasing proportion of muslim women wearing hijab and the lack of vitamin D fortification and fish consumption in Indonesia, it poses a problem for vitamin D deficiency among pregnant women. This study aimed at finding the best timing of UVB exposure and the duration of exposure which can be suggested to prevent vitamin D deficiency among pregnant women, for those wearing hijab or not. METHODS: This study recruited 304 pregnant women in the first trimester, 75-76 women from 4 cities of the most populated province, West Java, Indonesia which represented 70-80% percent of pregnancy per year. A 3-day notes on duration, time and type of outdoor activity and the clothing wore by the women were collected. UVB intensity radiation were obtained. Calculation on body surface area exposed to direct UVB radiation and UVB radiation intensity were done. Measurement of vitamin D level in sera were done on the same week. RESULTS: The median of maternal sera vitamin D level was 13.6 ng/mL and the mean exposed area was around 0.48 m2 or 18.59% of total body surface area. Radiation intensity reached its peak around 10.00 and 13.00, but the mean duration of exposure to UVB during this window was lower than expected. Significant correlation was found between maternal sera vitamin D level and exposed body surface area (r = 0.36, p < 0.002) or percentage of exposed body surface (r = 0.39, p < 0.001) and radiation intensity (r = 0.15, p = 0.029). Further analysis showed that duration of exposure to UVB should be longer for pregnant women wearing hijab as compared to women without hijab. CONCLUSION: This study suggested that the best timing to get UVB exposure was between 10.00-13.00, with longer duration for women wearing hijab (64.5 vs 37.5 min) of continuous exposure per day.

Systemic contact dermatitis due to corrosion of titanium-coated nickel and cobalt bone plate fixation: A case report.

RATIONALE: Corrosion refers to the degradation of a material that occurs following its interaction with other substances in the environment. Corrosion of metallic substances into tissues may lead to inflammatory responses such as systemic contact dermatitis (SCD), a skin condition where an individual who has previously been sensitized to a particular allergen via the cutaneous route will subsequently react to same allergen via the systemic route. This condition occurs following exposure to allergens such as metals, medications, and certain food substances. In recent years, the use of metal plates for internal fixation has become increasingly common in bone fracture repairs. PATIENT CONCERNS: A 34-year-old Indonesian male presented with systemic erythema with itching 7 days following a bone plate fixation as a management for mandibular fracture. DIAGNOSES: Physical examination showed pruritic red macules, papules, and scales on almost his entire body, along with facial swelling. The patch test results revealed a positive reaction to nickel and cobalt. Therefore, the patient was diagnosed with SCD. INTERVENTIONS: The patient was treated with topical and systemic corticosteroids as well as bone plate removal. OUTCOME: After treatment, the eruption turned brown, the itching was resolved, and there were no facial swelling as well. LESSONS: This case report highlights the need to consider the occurrence of SCD in patients following bone plate fixation.

Cutaneous Side Effects and Transepidermal Water Loss To Gefitinib: A Study of 11 Patients.

INTRODUCTION: Cutaneous side effects caused by epidermal growth factor receptor (EGFR) inhibitors occurred in 45-100% of patients which may lead to therapy modification or interruption. This study aimed to evaluate cutaneous side effects and transepidermal water loss (TEWL) values in non-small cell lung carcinoma (NSCLC) patients who received gefitinib EGFR inhibitor. METHODS: A descriptive observational study with cross-sectional design and a consecutive sampling method was conducted from 1 February to 4 March 2016. Eleven NSCLC patients with EGFR mutation who visited the Hemato-Oncology Clinic/Internal Medicine Department, Dr. Hasan Sadikin General Hospital, Bandung, Indonesia, were assessed through history taking, physical examination, and TEWL examination using Tewameter. RESULTS: Ten of the eleven patients experienced cutaneous side effects. The most frequently observed was xerosis cutis (8/10 patients), followed by acneiform eruptions (7/10 patients), and paronychia (3/10 patients). None of these patients experienced hair changes, mucositis, or drug hypersensitivity. Mean TEWL value of these patients was higher than normal (11.205 ± 1.881 g/m2/h). CONCLUSIONS: Patients who received gefitinib EGFR inhibitor experienced cutaneous side effects including xerosis cutis, acneiform eruptions, and paronychia, and have mean TEWL values higher than normal. Therefore, it might affect the skin barrier function.