A clinico-epidemiological study of different dermoscopic patterns in hyperpigmented facial lesions in a tertiary care centre.

Introduction: Facial pigmentation is a common presentation of patients attending dermatology out patient department (OPD) and is of great concern to patients. Facial pigmentation may be multifactorial and is only rarely diagnosed accurately by a detailed history and clinical examination. Pigmentary disorders cause psychological distress and negatively impact the quality of life of an individual. Aims and Objectives: (1) To study different dermoscopic patterns in facial melanosis. (2) To estimate the frequency of different dermoscopic patterns. Materials and Methods: Patients with facial hyperpigmentation attending the dermatology OPD were recruited after taking their written consent. A detailed history was taken to collect demographic data. Clinical examination and dermoscopy were done in all patients. Biopsy was done as and when required. Descriptive statistics has been used to describe the quantitative data. Qualitative data were presented as frequency and percentage for clinical and dermoscopic patterns. Results: The study included 100 patients with 15 different facial melanoses. The most common age group affected was 21-40 years in 53 (53%) cases. The female-to-male ratio was 1.63:1. Melasma was reported as the most common cause of facial melanosis constituting 49 (49%) of the total cases. Out of the total melasma cases, epidermal melasma constituted 22 (45%) cases, dermal melasma constituted four (4%) cases and mixed melasma constituted 23 (47%) cases. Other cases included were lichen planus pigmentosus (14; 14%), facial acanthosis nigricans (14; 14%), periorbital hyperpigmentation (7; 7%), post-inflammatory hyperpigmentation (4; 4%), exogenous ochronosis (2; 2%), lentigines (2; 2%), frictional melanosis (2;2%), and one case each of Becker's nevus, nevus of Ota, olanzapine-induced hyperpigmentation, Riehl's melanosis, macular amyloidosis, and tanning. Conclusions: Melasma was reported as the most common cause of facial melanosis. The most common dermoscopic feature was accentuated pseudopigment network. The study is beneficial in understanding the different clinical and dermoscopic patterns of facial melanosis, thus helping the physician to effectively manage the conditions and reduce the need of biopsy. Limitations: (1) A small sample size. (2) Histopathological correlation was not done in all cases.

Patient Perspectives of the Impact of Psoriatic Disease on Quality-of-Life in India: Sub-analysis from the Global Psoriasis and Beyond Survey.

Background: Psoriatic disease (PsD), including plaque psoriasis (PsO) and psoriatic arthritis (PsA), comprises a wide spectrum of manifestations and significantly impacts quality-of-life (QoL). Here, we assessed patients' understanding of PsO and PsA as a systemic disease, its impact on their physical and emotional well-being, and patients' experiences with healthcare professionals for shared treatment decision-making. Materials and Methods: The Global Psoriatic Disease and Beyond Survey was a cross-sectional, qualitative, online survey conducted on patients with moderate-to-severe PsO with/without concomitant PsA. This analysis reports findings from Indian patients. Results: Of the 261 surveyed patients, 27% with PsO reported concomitant PsA, of whom 89% reported PsA severity as moderately or highly active. Overall, 92% had heard the term "PsD," and 90% knew their condition was a systemic disease. Few were aware of PsD manifestations (palmoplantar psoriasis, 49%; nail psoriasis, 43%; axial symptoms, 40%; PsA, 34%) and comorbidities (cardiovascular disease, 33%; obesity, 30%; diabetes, 28%). Eighty-nine percent of patients indicated their skin problems had a "very-large" to "extreme-large" impact on QoL. Ninety-seven percent of patients experienced discrimination and stigmatization from others. Eighty-one percent of patients were not involved in deciding treatment goals. Few (PsO, 6%; PsA, 9%) patients were dissatisfied with current treatment; ≥50% patients reported incomplete relief of skin symptoms (PsO) and joint symptoms (PsA) as the reason for dissatisfaction. Conclusion: Lack of awareness of the manifestations and comorbidities associated with PsD and poor QoL highlights the need for patient education, shared treatment decision-making, and a multidimensional approach to PsD management in India.

IL-17A Orchestrates Reactive Oxygen Species/HIF1α-Mediated Metabolic Reprogramming in Psoriasis.

Immune cell-derived IL-17A is one of the key pathogenic cytokines in psoriasis, an immunometabolic disorder. Although IL-17A is an established regulator of cutaneous immune cell biology, its functional and metabolic effects on nonimmune cells of the skin, particularly keratinocytes, have not been comprehensively explored. Using multiomics profiling and systems biology-based approaches, we systematically uncover significant roles for IL-17A in the metabolic reprogramming of human primary keratinocytes (HPKs). High-throughput liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy revealed IL-17A-dependent regulation of multiple HPK proteins and metabolites of carbohydrate and lipid metabolism. Systems-level MitoCore modeling using flux-balance analysis identified IL-17A-mediated increases in HPK glycolysis, glutaminolysis, and lipid uptake, which were validated using biochemical cell-based assays and stable isotope-resolved metabolomics. IL-17A treatment triggered downstream mitochondrial reactive oxygen species and HIF1α expression and resultant HPK proliferation, consistent with the observed elevation of these downstream effectors in the epidermis of patients with psoriasis. Pharmacological inhibition of HIF1α or reactive oxygen species reversed IL-17A-mediated glycolysis, glutaminolysis, lipid uptake, and HPK hyperproliferation. These results identify keratinocytes as important target cells of IL-17A and reveal its involvement in multiple downstream metabolic reprogramming pathways in human skin.

Gigantic Melanocytosis - The Dark Enigma.

Gigantic melanocytosis is a rare and peculiar familial disorder of pigmentation. It presents as diffuse hyperpigmentation interspersed by raindrop-like hypopigmented macules predominantly involving the sun-exposed areas and later progressing to involve the photoprotected areas as well. All the cases described in the literature were observed to be commencing in the first year of life and were more common in males. Hereby, we report a 28-year-old female who presented with adult-onset gigantic melanocytosis with no similar familial history.

Vulvar Sarcomatoid Squamous Cell Carcinoma: A Rare Entity.

Vulvar squamous cell carcinoma with sarcomatoid features is an extremely rare histological variant of squamous cell carcinoma with co-existence of both epithelial and mesenchymal features. A 70-year-old woman presented with genital lesions for 4 months with associated burning and pain. Examination revealed well-defined bilaterally symmetrical hyperpigmented plaques on labia majora, fleshy erythematous growth on labia minora. Biopsy from the fleshy mass was suggestive of sarcomatoid malignancy. However, immunohistochemistry was positive for cytokeratin AE1/AE3 and negative for desmin and smooth muscle actin. Biopsy from hyperpigmented plaque was suggestive of Bowens disease. On the basis of histopathology and immunohistochemistry findings, diagnosis of vulvar sarcomatoid squamous cell carcinoma with Bowens disease was made and patient was started on external beam radiation therapy. Sarcomatoid squamous cell carcinoma of vulva is very rare cancer that has an aggressive and fatal course. Diagnosis has traditionally been difficult due to a large ratio of sarcomatous to squamous cell component. Due to its rarity, there are no distinct guidelines to direct therapy and care.

An unusual presentation of perianal Bowen's disease in an immunocompromised patient - Excised and grafted.

Bowen's disease also known as bowenoid keratoses, presents as a clinically persistent, progressive red scaly, or crusted plaque which is due to intraepithelial carcinoma and is potentially malignant. Lesions are typically asymptomatic but may be associated with bleeding. We are reporting perianal Bowen's disease in a 30-year-old married HIV-infected male which is excised and underlying healthy ulcer grafted.

Vulvar vestibular papillomatosis: A diagnostic conundrum.

Vulvar vestibular papillomatosis (VP) is considered a normal anatomical variant of the vulva. We present a 19-year-old girl with a history of "small itchy growths" on the vulva for 2 months without any associated discharge. These lesions were causing significant anxiety to the patient. Cutaneous examination revealed multiple, uniformly arranged, skin-colored, monomorphic micropapillae on the inner aspect of the labia minora. Biopsy showed mucosal hyperplasia with papillomatosis and loosely arranged subdermal tissue, no koilocytes were spotted. The diagnosis of vulvar VP was made. We want to highlight this clinical entity as most dermatologists are not familiar with this benign condition and easily confuse it with genital warts. This inexperience may result in unnecessary investigations causing psychological discomfort to the patient. We herein present such a case which brings out the diagnostic dilemma.

Efficacy and Safety Comparison of Basic Fibroblast Growth Factor-Related Decapeptide 0.1% Solution (bFGFrP) Plus Oral PUVA Combination Therapy with Oral PUVA Monotherapy in the Treatment of Vitiligo.

Background: Phototherapy in its different forms, is mainstay of vitiligo management. Combining treatment modalities like topical calcipotriol (for quicker, more intense repigmentation), Low dose azathioprine with PUVA have proven to be beneficial in management of vitiligo due to different mechanisms of repigmentation and their synergistic effects. Topical bFGF-related decapeptide (bFGFrP) application followed by sun exposure/ UVA phototherapy yields effective repigmentation. bFGFrP has shown to aid the targeted phototherapy in smaller lesions and its combinations with other treatment modalities have been very promising. However, there is paucity of studies on combination treatments; especially oral PUVA along with bFGFrP. This study was aimed at evaluating safety and efficacy of combination of bFGFrP with Oral PUVA in vitiligo (larger body surface area 20% or more). Materials and Methods: Phase IV, randomized, multicentre study (N = 120) in adult patients with stable vitiligo of 6 months treatment period with monthly follow up visits. Psoralen (Tab. Melanocyl) dosage 0.6 mg/kg orally 2 h before exposure to UVA phototherapy. Oral PUVA therapy, initially, at an irradiation dose 4 J/cm2 (PUVA group), followed by increments 0.5 J/cm2 every four sittings if tolerated for twice weekly. Primary end point was improvement in extent of repigmentation (EOR) in target lesion (at least 2 cm × 2 cm in greatest dimension, without leukotrichia), while secondary endpoints were improvement in patient global assessment (PGA) and safety at end of 6 months of treatment period in bFGFrP + oral PUVA combination group and Oral PUVA monotherapy group. Results: End of 6 months, significantly greater EOR >50%) was achieved in 61.8% (34 patients, n = 55) from combination group while 30.2% (16 patients, n = 53) from the oral PUVA monotherapy group (n = 53). Regarding Grade of repigmentation (GOR), complete repigmentation was observed 5.5% (3 patients, n = 55) in combination group whereas no patient showed complete repigmentation in monotherapy group (p ≤ 0.05), PGA showed significant overall improvement in combination group (p ≤ 0.05); 6 patients (10.9%) from combination group Vs one (1.9%) showed complete improvement. During treatment period, there were no reported adverse events. Conclusions: Addition of bFGFrP to oral PUVA therapy resulted in intense and faster induction of repigmentation than oral PUVA monotherapy with favorable safety profile.

Nailfold capillaroscopy as a prognostic marker for connective tissue diseases: An observational clinico-epidemiological study.

Background Nailfold capillaroscopy (NFC) is useful in the diagnosis and assessment of various connective tissue diseases. In this study, NFC findings were studied in patients of systemic sclerosis (SS), systemic lupus erythematosus (SLE) and dermatomyositis. Aims To study the nailfold capillaroscopic findings in patients with connective tissue disorders, their correlation with disease severity, and changes in findings following treatment or disease progression. Methods This observational prospective time-bound clinico-epidemiological study was conducted in 43 patients over 20 months at Topiwala National Medical College and BYL Nair Ch. Hospital, Mumbai. NFC was performed using the polarising mode of a USB 2.0 video-dermatoscope in all 10 fingernails at 50X and 200X. It was repeated at three follow-up visits to look for changes in findings. Results Among SLE patients, eleven (52.4%) had non-specific NFC patterns and eight (38.1%) had SLE patterns. Among systemic sclerosis patients, eight (42.1%) cases had active and late SS patterns respectively, while one (5.3%) each had SLE, non-specific and early SS patterns. After three follow-ups, 10 out of 11 (90.9%) cases with improvement in NFC also showed clinical improvement; this figure was significantly more than 11 out of 23 (47.8%) cases who had no change in NFC but showed clinical improvement. Two of the three dermatomyositis patients showed a non-specific pattern while one showed a late SS pattern at baseline. Limitations A larger sample size would have yielded results with more validity. Standardisation of the interval between baseline and last follow-up to equal to or more than six months would have yielded results with more accuracy. Conclusion Capillary findings change significantly over time and reflect changes in the clinical status of patients of both SLE and systemic sclerosis, and hence are an important prognostic marker. Rather than an overt change in NFC pattern, reduction or increase in abnormal capillaries is a better predictor of change in disease activity.

Sexually transmitted infections in pregnant women and their partners: A clinico-epidemiological study at a tertiary care center, Mumbai, Maharashtra.

Background: Sexually transmitted infections (STIs) during pregnancy are associated with adverse fetal outcome. They should be aggressively sought and treated. We did an analytical study with the primary aim to know the occurrence of STIs in pregnant women and their spouses. Materials and Methods: An observational cross-sectional analytical study of pregnant women with STIs and their spouses was conducted at a tertiary care hospital. Demographic parameters and medical history were recorded. Clinical examination and necessary investigations were done in pregnant females and their spouses. History about sexual behavior and knowledge of STIs were obtained from the questionnaire. Results: The prevalence of STIs in pregnant women was 2.1% (n = 61) out of 2894 pregnant women who attended our institute during the study period with the highest prevalence of HIV (1.1%), and out of 54 examined spouses, 32 spouses were suffering from STIs. Overall, women had poor awareness, knowledge of STIs, and preventive measures compared to men. A significant association was seen between level of education and awareness about HIV/AIDS and other STIs, both in pregnant women and their spouses. Conclusion: Our study showed an overall low prevalence of STIs among pregnant women but showed higher HIV and syphilis prevalence as compared to national prevalence. The serodiscordancy rate was found to be high in HIV, syphilis, and hepatitis B.

A Joint Consensus of Rheumatologists and Dermatologists on Early Detection and Effective Management of Psoriatic Arthritis: India's Perspective.

Psoriatic arthritis (PsA) is a chronic inflammatory disease with clinical manifestations, including inflammatory arthritis and the presence of psoriasis (PsO). The present consensus statement evaluated the early diagnosis and treatment approaches in the management of psoriasis and psoriatic arthritis by rheumatologists and dermatologists. For PAN India representation, a panel of eight rheumatologists and five dermatologists from different institutes in India were constituted. These thirteen experts were divided into two groups (rheumatologists group and dermatologist group) who received a set of questionnaires each for diagnosis and treatment approaches in the management of psoriasis and psoriatic arthritis. Based on the responses received, a panel discussion took place, where the experts identified the early diagnostic criteria for PsA considering: Clinical signs and symptoms, and questionnaire-based PsA screening, which includes Psoriasis Epidemiology Screening Tool (PEST) for dermatologists and Classification Criteria for Psoriatic Arthritis (CASPAR) for rheumatologists. The experts also recommended shift from conventional disease-modifying anti-rheumatic drugs (DMARDs) to biologics like secukinumab, when there is extensive skin involvement and TNF inhibitors when there is extensive joint involvement. Overall, the objective of the consensus was to assist rheumatologists and dermatologists in the early diagnosis and management of patients of PsA and PsO in their clinical practice.

A Rare Case of Multidrug-Resistant Lupus Vulgaris with a Mixed Pattern of Resistance - A Long Journey to Diagnosis and Treatment.

An 18-year-old male presented with a single round to oval well-defined irregular erythematous plaque 10 cm × 6 cm, with a verrucous surface, central atrophy, and crusting at the periphery on the right knee of one-year duration. The patient had received ATT (anti-tubercular treatment) twice in the past without any improvement. MGIT (mycobacteria growth indicator tube) and CBNAAT (Cartridge-based nucleic acid amplification test) were performed, and drug sensitivity testing was done, which led to a diagnosis of multidrug resistance (MDR) with a mixed pattern. The management of cutaneous tuberculosis (TB) is becoming difficult due to an increase in resistance to category-I ATT. Patients harboring MDR and extensively drug-resistant (XDR) strains present a fearsome challenge for the clinician. A cure is possible with early identification of resistance and the use of an appropriate regimen.

Clinical and histopathological aspects of lichenoid dermatitis in patients of retroviral diseases.

Context: Lichen planus (LP) is known to be associated with viral infections such as hepatitis B and C, but its association with HIV is rarely reported. Lichenoid drug eruptions have been implicated as the side effects of anti-retroviral therapy. Aims and Objectives: The aim of this study is to study demographics, clinical, histological, and immunological profile of the HIV patients presenting with lichenoid dermatitis. Subjects and Methods: HIV patients presenting with LP such as lesions were evaluated with complete history and physical examination. Demographic profile of patients was studied with features such as age, sex, duration of disease, distribution of the lesions, CD4 count, concomitant medications, associated comorbidities, and response to the treatment. Results: Twenty-one HIV patients presenting with LP such as lesions were studied. Of these, 20 patients had LP and one patient had lichenoid drug reaction. The age of the patient ranged from 40 to 60 years with no sex predilection. The duration of lesions ranged from 15 days to 7 years. Eleven patients had simultaneous cutaneous and oral involvement, five patients had only oral involvement and four patients of LP and one patient of lichenoid drug reaction had only cutaneous lesions. All the patients were on antiretroviral therapy, mainly on lamivudine, zidovudine, and nevirapine. Almost all the patients had CD4 count of more than 250 at the time of presentation. One patient was diagnosed to have lupus erythematosus and LP overlap. Patients were treated with oral medications such as corticosteroids, methotrexate, and dapsone and topical medications such as corticosteroids and calcineurin inhibitors. Conclusions: The appearance of LP such as lesions in HIV patients is a rare occurrence with 11 cases of LP reported till date. Our case series of 20 patients will throw light on possible etiology and difficulties in the management of LP such as lesions in HIV patients.

Bowen's disease on two different unrelated anatomical sites (genitals and nail) in succession in an immunocompromised patient.

Bowen's disease (BD) is a premalignant condition. Its exact etiology is unknown but chronic arsenic and sun exposure, and human papillomavirus infection is known predisposing factors. Pigmented lesions of BD represent 1.7%-5.5% of all BD cases. BD in the nail unit is challenging due to its varied clinical presentations such as fissure, ulceration, warty lesion, paronychia, onychocryptosis, and nail dystrophy. We present the case of a 43-year-old married, immunocompromised male (HIV), with a CD 4 count of 478, on tenofovir, atazanavir boosted with ritonavir regimen, known diabetic presented with multiple asymptomatic discrete, rounded, hyperpigmented verrucous papules on both surfaces of shaft of penis and scrotum and a single, 4 cm × 3 cm, irregular, smooth surfaced, hyperpigmented plaque, on the base of the penis extending to the upper part of the scrotum of 1-year duration with history of multiple unprotected sexual exposures with unknown female partners. Regional lymphadenopathy and systemic complaints were absent. Biopsy from hyperpigmented verrucous papule and hyperpigmented plaque was consistent with verruca vulgaris and pigmented Bowen's disease, respectively. The patient was lost to follow-up. Ten months later, he presented with longitudinal melanonychia with a subungual hyperpigmented mass protruding beyond the distal nail margin near the lateral nail fold of the right middle finger nail with an absent Hutchinson's sign. Longitudinal excisional biopsy of nail lesion was consistent with BD. He was started on 5-fluorouracil 5% for BD of genitals and podophyllin application for verruca vulgaris with remarkable improvement in both the lesions and there is no recurrence of nail lesion after 9 months of excision.

Determinants of Ligand Specificity and Functional Plasticity in Type I Interferon Signaling.

The Type I Interferon family of cytokines all act through the same cell surface receptor and induce phosphorylation of the same subset of response regulators of the STAT family. Despite their shared receptor, different Type I Interferons have different functions during immune response to infection. In particular, they differ in the potency of their induced anti-viral and anti-proliferative responses in target cells. It remains not fully understood how these functional differences can arise in a ligand-specific manner both at the level of STAT phosphorylation and the downstream function. We use a minimal computational model of Type I Interferon signaling, focusing on Interferon-α and Interferon-ß. We validate the model with quantitative experimental data to identify the key determinants of specificity and functional plasticity in Type I Interferon signaling. We investigate different mechanisms of signal discrimination, and how multiple system components such as binding affinity, receptor expression levels and their variability, receptor internalization, short-term negative feedback by SOCS1 protein, and differential receptor expression play together to ensure ligand specificity on the level of STAT phosphorylation. Based on these results, we propose phenomenological functional mappings from STAT activation to downstream anti-viral and anti-proliferative activity to investigate differential signal processing steps downstream of STAT phosphorylation. We find that the negative feedback by the protein USP18, which enhances differences in signaling between Interferons via ligand-dependent refractoriness, can give rise to functional plasticity in Interferon-α and Interferon-ß signaling, and explore other factors that control functional plasticity. Beyond Type I Interferon signaling, our results have a broad applicability to questions of signaling specificity and functional plasticity in signaling systems with multiple ligands acting through a bottleneck of a small number of shared receptors.

Presence and the roles of IL-9/Th9 axis in vitiligo.

Immune dysregulation is critical in vitiligo pathogenesis. Although the presence and roles of numerous CD4+ T-cell subsets have been described, the presence of Th9 cells and more importantly, roles of IL-9 on melanocyte functions are not explored yet. Here, we quantified the T helper cell subsets including Th9 cells in vitiligo patients by multicolor flowcytometry. There was an increased frequency of skin-homing (CLA+ ) and systemic (CLA- ) Th9 cells in vitiligo patients compared to healthy donors. However, there was no difference in Th9 cell frequency in vitiligo patients with early and chronic disease. There was negligible IL-9 receptor (IL-9R) expression on human primary melanocytes (HPMs); however, IFNγ upregulated IL-9R expression on HPMs. Functionally, IL-9/IL-9R signaling reduced the production of IFNγ-induced toxic reactive oxygen species (ROS) in HPMs. There was no effect of IL-9 on expression of genes responsible for melanosome formation (MART1, TYRP1, and DCT), melanin synthesis (TYR), and melanocyte-inducing transcription factor (MITF) in HPMs. In conclusion, this study identifies the presence of Th9 cells in vitiligo and their roles in reducing the oxidative stress of melanocytes, which might be useful in designing effective therapeutics.

Multiomics Analysis and Systems Biology Integration Identifies the Roles of IL-9 in Keratinocyte Metabolic Reprogramming.

IL-9‒producing T cells are present in healthy skin as well as in the cutaneous lesions of inflammatory diseases and cancers. However, the roles of IL-9 in human skin during homeostasis and in the pathogenesis of inflammatory disorders remain obscure. In this study, we examined the roles of IL-9 in metabolic reprogramming of human primary keratinocytes (KCs). High-throughput quantitative proteomics revealed that IL-9 signaling in human primary KCs disrupts the electron transport chain by downregulating multiple electron transport chain proteins. Nuclear magnetic resonance-based metabolomics showed that IL-9 also reduced the production of tricarboxylic acid cycle intermediates in human primary KCs. An integration of multiomics data with systems-level analysis using the constraint-based MitoCore model predicted marked IL-9-dependent effects on central carbohydrate metabolism, particularly in relation to the glycolytic switch. Stable isotope metabolomics and biochemical assays confirmed increased glucose consumption and redirection of metabolic flux toward lactate by IL-9. Functionally, IL-9 inhibited ROS production by IFN-γ and promoted human primary KC survival by inhibiting apoptosis. In conclusion, our data reveal IL-9 as a master regulator of KC metabolic reprogramming and survival.

Birt-Hogg-Dubé syndrome - an unique case series.

Birt-Hogg-Dubé syndrome (BHDS) is an uncommon autosomal dominant syndrome. It is also known as Hornstein-Knickenberg syndrome. It is an inherited disorder culminating in mutations in folliculin coding gene (FLCN). The clinical exhibitions of the syn-drome are multi-systemic, comprising of a constellation of pulmonary, dermatologic and renal system manifestations. The most common presentations include fibrofolliculomas, renal cell carcinomas, lung cysts and spontaneous pneumothorax. The treatment is conservative with regular monitoring of the renal and lung parameters. Fibrofolliculomas may require surgical excision and recurrent events of pneumothorax may warrant pleurodesis. We reported a case series of 2 patients presenting with symptoms of progressive breathlessness along with dermatological manifestations and subsequently showing radiological manifestations of Birt-Hogg-Dubé syndrome in the form of lung cysts.