Clinical Use of Super Bioavailable Itraconazole for the Management of Dermatophytosis: Consensus Statement by Dermatologists from India via the Modified Delphi Technique.

INTRODUCTION: Super bioavailable itraconazole (SB ITZ) overcomes the limitations of conventional itraconazole (CITZ) such as inter-individual variability and reduced bioavailability. It has been approved for systemic mycoses in Australia and Europe as 50mg and the United States as 65mg and in India as 50mg, 65mg, 100mg, and 130mg. However, data on the ideal dose and duration of SB ITZ treatment in managing dermatophytosis is insufficient. This consensus discusses the suitability, dosage, duration of treatment, and relevance of using SB ITZ in managing dermatophytosis in different clinical scenarios. METHODS: Sixteen dermatologists, (>15 years of experience in the field and ≥2 years clinical experience with SB ITZ) formed the expert panel. A modified Delphi technique was employed, and a consensus was reached if the concordance in response was >75%. RESULTS: A total of 26 consensus statements were developed. The preferred dose of SB ITZ is 130mg once daily and if not tolerated, 65mg twice daily. The preferred duration for treating naïve dermatophytosis is 4-6 weeks and that for recalcitrant dermatophytosis is 6-8 weeks. Moreover, cure rates for dermatophytosis are a little better with SB ITZ than with CITZ with a similar safety profile as of CITZ. Better patient compliance and efficacy are associated with SB ITZ than with CITZ, even in patients with comorbidities and special needs such as patients with diabetes, extensive lesions, corticosteroid abuse, adolescents, and those on multiple drugs. CONCLUSION: Expert opinions indicate that overall clinical experience with SB ITZ is better than that with CITZ.

Nail Society of India Recommendations for Treatment of Onychomycosis in Special Population Groups.

Onychomycosis (OM) is a difficult-to-treat condition, especially considering the limited armamentarium of antifungal drugs, need for prolonged treatment, and poor compliance. This problem is further confounded while treating OM in special populations such as children, elderly, immunosuppressed patients, pregnant or lactating women, and patients with chronic liver or kidney disease. In the absence of standardized treatment guidelines, the antifungal therapy is either withheld or compromised, as it is largely governed by personal preferences or based on anecdotal reports. Hence, an expert group of the Nail Society of India worked towards drafting guidelines based on established literature and inputs from experts, with practical recommendations for the treatment of onychomycosis in special population groups. An extensive analysis of available English language literature on onychomycosis in special populations, published during a 10-year period (2014-2023 until date) was done. The available studies and reports were evaluated, cross-references read, and evidence compiled, graded, and discussed by the expert group to derive consensus recommendations for practice. The evidence and recommendations based on it are presented in a narrative format to guide treatment choices when dealing with population groups with special considerations.

A Study of Community-Acquired Pyodermas with Special Reference to Panton-Valentine Leukocidin (PVL)-Positive Methicillin-Resistant Staphylococcus Aureus.

Background: Community-acquired (CA) pyodermas are one of the most common infections encountered in the dermatology outpatient clinics. A significant number of these conditions are caused by Staphylococcus aureus. CA-methicillin-sensitive Staphylococcus aureus (MSSA) and CA-methicillin-resistant Staphylococcus aureus (MRSA) have specific virulence genes which are associated with these diseases, particularly the Panton-Valentine leukocidin (PVL) genes. The presence of the PVL gene as a virulence factor may be associated with recurrent and severe skin infections. Materials and Methods: A prospective study was conducted with 205 cases of CA pyodermas, of which five were discarded due to mixed isolates. Clinical details were taken and wound exudate was sent for bacteriological examination. Further, the molecular study was performed on all MRSA (7) isolates and 13 randomly selected MSSA isolates using polymerase chain reaction for mecA and PVL genes. Results: Staphylococcus aureus was the most common organism (90%) isolated from primary or secondary CA pyodermas. The prevalence of CA-MRSA among all pyodermas was 3.5% in our community. The PVL gene was not detected in all tested CA-MRSA and CA-MSSA isolates. Conclusion: While pyodermas are common, the prevalence of MRSA is low in the CA pyodermas in our region. PVL does not appear to be a virulence factor among the isolated MRSA. Larger, multicentric, and periodic studies are, however, required to further justify these claims.

IADVL SIG Recalcitrant Dermatophytosis Position Statement on Super Bioavailable Itraconazole.

Itraconazole (ITZ) has been the mainstay of oral antifungal treatment for the current epidemic of recalcitrant dermatophytosis (RD) in India. Recently, a newer formulation of ITZ, super bioavailable itraconazole (SUBA-ITZ), is made available in the market by many pharmaceutical companies. It is important for dermatologists to understand the pharmacokinetic properties of SUBA-ITZ vis-a-vis conventional pellet formulation to use it effectively and safely. Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) has established a special interest group for recalcitrant dermatophytosis (SIG-RD) to strengthen research, continuing medical education, and industry collaboration on the subject. This position statement on SUBA-ITZ by SIG-RD is an attempt to address current pieces of evidence and the position of this new formulation in the management of RD.

Comparative Efficacy and Safety of Super-Bioavailable Itraconazole-130 mg Once Daily in Obese and Non-Obese Patients of Glabrous Tinea.

Background: Obesity is considered one of the risk factors for dermatophytosis and warrants systemic therapy. Itraconazole is the most commonly used antifungal, but owing to pharmacokinetic challenges, super-bioavailable itraconazole (SITZ) was approved globally, recently. For the management of dermatophytosis in obese patients, there are mixed opinions regarding the dosing of systemic antifungals. Materials and Methods: This study was conducted to compare the efficacy and safety of SITZ-130 mg once daily in glabrous tinea or dermatophytosis in obese and non-obese patients for a total duration of 10 weeks on 87 eligible patients. Efficacy and safety assessments were done at weeks 3 and 6 with follow-up at week 10 for relapse. The primary objective was to assess the proportion of patients achieving complete cure at week 6 with the assessment of safety, clinical, and mycological cure rates as secondary objectives. Results: Out of 87 patients, 80 were considered for analysis. At week 6, 22/35 (63%) and 33/45 (73%) patients in obese and non-obese groups were completely cured (P = 0.47). Similarly, there was no statistically significant difference for mycological and clinical cure in both the groups (P = 0.17 and P = 0.61, respectively). Four patients in the obese group (18% of completely cured), while one patient in the non-obese group (3% of completely cured), relapsed within 4 weeks of completion of treatment (P = 0.14). The therapy was well tolerated by both groups, with only one patient in the non-obese group experiencing pruritus. Conclusion: SITZ-130 mg once daily achieved desired and similar clinical response in obese patients as of non-obese patients suffering from dermatophytosis, and hence, a higher dose may not require in obesity.

Chromoblastomycosis: A Case Series and Literature Review.

Chromoblastomycosis is a subcutaneous mycosis caused by a variety of dematiaceous fungi. Fonsecaea (F.) pedrosoi is the most common causative agent. Majority of cases have been reported from tropical and subtropical regions with rural and agricultural background. It is a chronic disease with low incidence of complications but is very refractory to therapies. This is a case series of 22 cases of chromoblastomycosis from two health-care facilities in India. Information regarding the history, clinical presentations, diagnostic methods, therapy, and outcome of treatment were retrieved. Preponderance was seen among the males and in the age group of 41-60 years. Manual and agricultural laborers were commonly affected. Lower extremities were the most common sites affected. Morphological patterns like verrucous plaque, psoriasiform plaque, and verrucous nodules were seen. Direct microscopy with potassium hydroxide (KOH) mount was positive in all the cases. Histopathology in all cases displayed suppurative granulomatous inflammation with pigmented fungal cells. Fungal culture was positive in 10 cases with F. pedrosoi being the commonest agent. Antifungal treatment alone was instituted in 10 cases, cryotherapy along with antifungal therapy was given in 9 cases, and surgical excision was done in 3 cases. Complete clinical cure was achieved in seven cases. Chromoblastomycosis is characterized by chronicity, diverse clinical presentations, and therapeutic recalcitrance. Direct KOH mount of the black dots forms an important bedside tool in the diagnosis. Long-term antifungal therapy along with adjuvant cryotherapy may be the best option for the management.

Efficacy of Super-Bioavailable Itraconazole and Conventional Itraconazole at Different Dosing Regimens in Glabrous Tinea Infection - A Randomized Clinical Trial.

Introduction: Itraconazole follows non-linear pharmacokinetics and hence is recommended once daily, but in real-world practice, is commonly prescribed as twice daily. Hence, this study aimed to evaluate the efficacy and safety of super-bioavailable-itraconazole-130 mg (SB-130) and conventional-itraconazole-200 mg (CITZ-200) once daily compared with conventional-itraconazole-100 mg (CITZ-100) twice daily in glabrous tinea. Methods: A total of 261 eligible patients were enrolled in this prospective, randomized, clinical study from December-2021 to August-2022 at seven centers in India. Efficacy and safety assessments were done at week-3 and 6, with follow-up at week-10 for relapse. The primary objective was to assess the proportion of patients who achieved complete cure at week-6 following treatment in all itraconazole groups. The secondary outcomes were safety and clinical and mycological cure rates. Results: Of 261 patients, 240 were included in the analysis. At week-6, 140 patients were completely cured; thus, overall cure rate was 58.33%. Fifty-five patients (69%) in SB-130 while 47/77 (61%) and 38/83 (46%) patients were completely cured in CITZ-200 and CITZ-100 groups respectively (p<0.05; SB-130: CITZ-100, p=0.32; SB-130: CITZ-200, p=0.058; CITZ-200: CITZ-100). There was no statistical difference in the mycological cure rate and area clearance rate between any of the groups (p=0.14); however, a statistically significant difference was noted for OD dosing over BD dosing in achieving clinical cure rates (p<0.05). A total of 13/140 patients (9%) relapsed following complete cure, with no statistically significant difference between any of the groups (p=0.50). All treatments were safe and well-tolerated, with no discontinuation. Conclusion: In this clinical study, moderate efficacy with all doses of ITZ was reported but was better with OD dosing. Although there was no statistical difference between SB-130 and CITZ-200, SB-130 may be preferred over CITZ-200 owing to the advantage of SB over the conventional ITZ.

Management of Dermatophytosis: Real-World Indian Perspective.

Background: In spite of the availability of multiple consensus statements on dermatophytosis management, different treatment approaches have been experienced in India and require more scrutiny to further update guidelines and improve patient care. Aim: To determine the different approaches in dermatophytosis diagnosis and management among dermatologists in India. Materials and Methods: A web-based questionnaire was created and validated by five panelists with experience of >15 years in dermatophytosis and then circulated to about 2,000 dermatologists in India in September 2021 for a real-world management scenario. Results: Out of 2,000 dermatologists, 459 responded. About half of the dermatologists (51%) routinely conduct potassium hydroxide mount (KOH) at the initiation of therapy. Similarly, about 53% of dermatologists initiate the management of dermatophytosis with combination therapy in all types of dermatophytosis for 4-6 weeks depending upon severity. Different types of combinations are being practiced, such as either two systemic and one topical, two topicals and one systemic, but the combination of one systemic and one topical (69%) is the most commonly practiced. Itraconazole (100 mg twice a day) and luliconazole are the most commonly prescribed antifungal medications. In case of non-response to routine dose of systemic anti-fungals, about 72% of dermatologists up dose them. Most of them continue these drugs for additional 1-2 weeks after clearance of the disease. Additionally, keratolytics and moisturizers are commonly prescribed. Additionally, 62% advise liver function tests (LFTs) at the initiation of therapy, whereas 72% advise monitoring adverse effects due to systemic antifungal drugs during treatment. Conclusion: Combination therapy stood out as the need of the hour in the current menace of dermatophytosis with timely monitoring of laboratory tests for adverse events due to the use of systemic antifungals for a longer duration.

A Clinical, Dermoscopic, and Histopathological Study of Follicular Psoriasis.

Introduction: Follicular psoriasis is one of the underdiagnosed clinical types of psoriasis. Literature is grossly limited to anecdotal case reports and series. Clinical and investigational aspects are not studied in depth. Materials and Methods: A study was conducted to determine the frequency of follicular psoriasis, which includes cases with an exclusive or substantial number of follicular lesions. We analyzed the clinical, dermoscopic, and histopathological features of follicular psoriasis in a descriptive study. Results: A total of 117 patients with psoriasis were screened. An exclusive or substantial number of follicular lesions were found in 22 patients. Four patients had exclusively follicular lesions and others were psoriasis vulgaris with follicular psoriasis. Dermoscopy revealed perifollicular scaling and white homogeneous area with normal terminal hair in all cases. Vascular features were visible in 14 cases and all had dotted vessels, with four having additional globules. Twenty patients revealed one or more features suggestive of follicular psoriasis on histopathology. Conclusion: Follicular lesions can appear exclusively or can coexist with plaque type of lesions in psoriasis. They may indicate early psoriasis lesions. Dermoscopy is a useful and rapid tool to confirm the diagnosis of follicular psoriasis. Histopathology, though confirmatory, demands an astute interpretational skill. Diagnosis of follicular psoriasis can have therapeutic implications.

Evaluation of serum proteome from Indian psoriasis patients.

Psoriasis is a polygenic chronic skin condition, associated with many systemic disorders. Though it is most studied dermatological condition, molecular mechanism leading to its pathogenesis is still unclear. An insight into its proteome may help unrevealing some biomarkers and therapeutic targets. In this study, we carried out mass spectrometry based quantitative proteomic analysis of serum from psoriasis patients by employing Tandem Mass Tags (TMT) approach. We identified 861,887 MS/MS spectra corresponding to 493 proteins. These dysregulated proteins were further classified by Gene Ontology and protein-protein interaction of dys-regulated proteins revealed networks in psoriasis patients.

Relevance of Inflammatory Cytokine mRNA Expression of Tumour Necrosis Factor- Alpha (TNF α), Interleukin 17A (IL 17A) and Interleukin 6 (IL 6) in Indian Patients with Psoriasis.

Background: Psoriasis, a chronic, immune-mediated skin disorder, has systemic manifestations as well as an ample negative impact on the quality of life (QOL) of the patient. An abnormal proliferation of keratinocyte and dermal infiltration by immune cells is a characteristic feature. It involves components of both innate and adaptive immunity, and the interaction of T cells with macrophages. Keratinocytes and dendritic cells are mediated by the secreted cytokines. This study was taken up to look into changes at the molecular level that occur during the expression of three cytokines namely tumour necrosis factor-alpha (TNFα), interleukin 17A (IL-17A) and interleukin 6 (IL-6) in Indian patients with psoriasis. Methods: A case-control study was conducted with samples from 15 psoriasis vulgaris patients and 10 healthy control subjects. Clinical parameters were recorded. Blood samples were analysed for peripheral blood messenger ribonucleic acid (mRNA) expression of TNFα, IL-17A and IL-6 using real-time polymerase chain reaction (RT-PCR). Results: The mRNA expression of TNFα, IL-17A and IL-6 in psoriasis patients were increased as compared to that in normal subjects. Conclusions: The elevated levels of Interleukins indicates a systemic inflammatory process that is akin to the cutaneous inflammation. This study indicates that the targeted therapies against these cytokines are likely to be beneficial in Indian psoriasis patients.

A multicentric clinical and epidemiological study of chronic and recurrent dermatophytosis in India.

BACKGROUND: There has been an alarming increase in the prevalence of chronic, recurrent and steroid modified dermatophytosis of the glabrous skin in the recent years in India. There is paucity of literature on the magnitude of this major public health problem. OBJECTIVE: To estimate the prevalence of dermatophytosis and clinico-epidemiological features of chronic and recurrent dermatophytosis (CRD) across India and to evaluate the associated risk factors. METHODS: This is a multicentric descriptive cross-sectional study conducted in 13 centres situated across India in two phases during dry and rainy seasons. All consecutive patients presenting with dermatophytosis were screened during the study period of 14 consecutive working days. Patients with CRD of the glabrous skin as per the case definition were included after exclusion of isolated hair and nail infections. Demography, clinical findings and results of potassium hydroxide wet mount were recorded. RESULTS AND CONCLUSION: A total of 41,421 patients were screened, out of which 7174 (17.31%) patients had glabrous dermatophytosis. CRD was observed in 1999 (27.86%) patients with 78.08% and 21.95% of chronic and recurrent dermatophytosis, respectively. Family history was present in 50.03% of patients. History of sharing of fomites was present in 50.37% of them. Synthetic tight clothes were worn by 43.47%, while 50.9% gave history of misuse of topical corticosteroid creams. Multiple site involvement was common (69.58%) with tinea cruris (79.99%) and tinea corporis (75.69%) being the most common clinical types. CRD is associated with sharing of fomites, topical corticosteroid misuse and involvement of multiple sites.

Onycho-mucocutaneous syndrome secondary to human immunodeficiency virus disease.

Cutaneous, mucosal, and nail examination is the key to unveiling a plethora of systemic diseases. Mucocutaneous lesions directly related to human immunodeficiency virus (HIV) infection usually present as initial manifestations of immune deficiency, of which few lesions act as predictors of an immunocompromised state. Here, we report two cases who presented with onycho-mucocutaneous symptoms which raised the suspicion of and invariably led to the diagnosis of an underlying immunosuppression secondary to HIV infection.

An Open-Label, Randomized, Double-Arm Clinical Trial to Compare the Effectiveness and Safety of Super Bioavailable Itraconazole Capsules and Itraconazole Capsules in the Management of Dermatophytosis in India.

PURPOSE: A new oral formulation of itraconazole, called super bioavailable itraconazole (SBITZ), has been launched in India, exhibiting greater bioavailability than conventional itraconazole (CITZ). No clinical studies on its effectiveness and safety in dermatophytosis in comparison with CITZ have been conducted in India. Hence, the aim of this clinical study was to compare the effectiveness and safety of SBITZ capsules and CITZ capsules in dermatophytosis. PATIENTS AND METHODS: This was an open-label, randomized, double-arm clinical study in which 70 patients (≥18 years of age) of either gender and diagnosed with tinea cruris, tinea corporis, and/or tinea faciei were included. The study was divided into two parts, the first part comprising a treatment period of 4 weeks and the second part an observation period for recurrence, comprised of another 4 weeks, thus making an entire study duration of 8 weeks. RESULTS: Of the 70 patients enrolled in this study, 59 (33 patients in the CITZ group and 26 patients in the SBITZ group) were included in the final analysis. In both groups, most patients were diagnosed with tinea cruris et corporis, with five or more lesions. At week 4, 11 patients (33.33%) and 17 patients (65.38%) had achieved complete cure (p<0.05), whereas 22 patients (66.67%) and 22 patients (84.61%) had achieved mycological cure (p=0.14), in the CITZ and SBITZ groups, respectively. During the observation period, recurrence was seen in 1/11 and 4/17 completely cured patients in the CITZ and SBITZ groups, respectively (p=0.15). A significant difference was noted in resolution of symptoms as well as lesions of dermatophytosis in the SBITZ group (p<0.05). Both treatments were found to be safe and well tolerated. CONCLUSION: In the light of real-world evidence on effectiveness and safety, SBITZ should be considered as a potent therapeutic choice to effectively control the current menace of dermatophytosis in India.

Efficacy and Safety of Novel Formulation of Clobetasol Propionate 0.025% Cream in Indian Moderate-to-Severe Psoriasis Patients: Phase-2a, Randomized 3-Arm Study.

INTRODUCTION: Clobetasol propionate (0.05% standard dose formulation), a topical corticosteroid, leads to systemic side-effects like hypothalamic-pituitary-adrenal (HPA) axis suppression at doses as low as 2 g/day. The aim of this study was to evaluate HPA axis suppression, efficacy, and safety of clobetasol propionate (0.025%, formulation 5 and 13) versus currently marketed 0.05% cream in Indian patients with moderate-to-severe psoriasis. METHODS: In this phase 2a investigator-blinded study, patients aged ≥ 18 years with moderate-to-severe psoriasis were randomized 1:1:1 to receive clobetasol propionate 0.025% formulation 5, or 13, or 0.05% cream; twice daily for 28 days. Safety endpoints included adrenocorticotropic hormone (ACTH) test results at day 28 (primary), and local tolerability at each visit (burning/stinging/pruritus, secondary). Efficacy endpoints included Psoriasis Global Assessment (PGA) score. RESULTS: Overall, 88 patients received clobetasol propionate 0.025% formulation 5 and 13 (n = 29 for both) and 0.05% cream (n = 30). At day 28, the proportion of patients with an abnormal ACTH stimulation test (cortisol levels ≤ 18 µg/dl) was numerically lower in 0.025% formulations: 5 (20.7%) and 13 (17.2%) compared with 0.05% cream (30.0%), (p = 0.320). Decrease in burning/stinging /pruritus scores were comparable in all treatment groups and PGA success rates were higher with 0.025% formulations: 5 (38.9%) and 13 (36.8%) compared with 0.05% cream (30.8%). CONCLUSION: Clobetasol propionate 0.025% could be an effective treatment for moderate-to-severe psoriasis compared with 0.05% cream, demonstrating comparable efficacy with a better systemic safety profile. TRIAL REGISTRATION NUMBER: REF/2018/01/016779.

A cross-sectional study on clinico-dermoscopic features of periorbital melanosis in a tertiary care hospital.

INTRODUCTION: Periorbital melanosis (POM) is an esthetic facial concern on increasing trend and has a severe emotional impact on patients. We aimed to study the clinical and dermoscopic patterns of periorbital melanosis to aid in the classification and strategize therapy. METHODS: A cross-sectional, observational study was conducted on one hundred patients with POM in a tertiary care center in India from January 2020-March 2020. Dermoscopic assessment of POM was done using video dermatoscope- FotoFinder Medicam 1000s (magnification up to 140x). RESULTS: The mean age of participants was 32.8 ± 9 years. It was more prevalent among females (78%). The constitutional type (43%) of POM was the most common followed by shadow-effect type (32%). The various dermoscopic pigmentary patterns seen were scattered pigmented dots (56%), exaggerated pigment network (31%), globules (30%), and blotches (27%). Dilated veins and telangiectasia were seen in 50% and 32% of subjects, respectively. Exaggerated skin markings were seen in 43% of participants. Scattered pigmented dots were most commonly seen in constitutional, vascular, and shadow types but were significantly associated with vascular type. Exaggerated pigment network was the most frequent pigmentary pattern in post-inflammatory type of POM. Globules were significantly associated with constitutional as well as shadow type of POM and blotches with shadow type of POM. CONCLUSIONS: Periorbital melanosis presents as multifactorial entity with constitutional type being the most common. The dermoscopic patterns of POM may provide a clue to the underlying etiology, thereby helping to plan appropriate treatment.