Nail fold capillaroscopy in leprosy: Unveiling the microvascular changes.

BACKGROUND: Leprosy, a chronic infectious disease, is associated with various nail changes. Its etiopathogenesis is multifaceted, with microvascular damage being crucial. Nail fold capillaroscopy (NFC) emerges as a novel tool for detecting early vascular deficits in leprosy. The study aimed to assess and provide a complete clinical characterization of NFC changes in leprosy patients. METHODS: It is an observational cross-sectional study, done over a period of 1.5 year (January 2021 to august 2022) in a tertiary care hospital, encompassing 60 patients diagnosed with leprosy (18-60 years). After obtaining informed consent; detailed history, complete cutaneous and neurological examinations were conducted. All fingernails and toenails were examined for clinical changes. Subsequently, onychoscopy was performed using USB type of video-dermatoscope (Model AM7115MZT Dino-lite), a non-invasive tool. This was followed by NFC which was done for all fingernails and images were recorded by single operator, which were then assessed for quantitative and qualitive changes and statistical analysis was conducted using SPSS v20, with mean capillary density compared using Student's t-test, morphological change frequencies assessed by proportions, and group comparisons made using Chi-square or Fischer exact tests, with a significance threshold of p < 0.05. RESULTS: Among the 60 patients, 39 were in the lepromatous group, which included both borderline lepromatous (BL) and lepromatous leprosy (LL) patients, and 17 were in the tuberculoid group, which included borderline tuberculoid (BT) leprosy patients; 23.3 % had Type 1 reactions, and 18.3 % had Type 2 reactions. Nail fold capillaroscopy (NFC) showed microvasculature changes in 93.3 % of patients. The average capillary density was 6.8 ± 1.5 capillaries per mm, with the lepromatous group having a lower density (6.5 ± 1.09) compared to the tuberculoid group (7.0 ± 0.86). The most common NFC changes in the tuberculoid group were tortuous capillaries (70 %), capillary dropouts, and dilated capillaries (both 64.7 %). In the lepromatous group, capillary dropouts (82 %) were most frequent, followed by tortuous (69 %), receding (69 %), and dilated capillaries (66 %). A dilated and prominent subpapillary plexus was more common in the lepromatous group (35 %, p = 0.04). Patients with trophic changes in the lepromatous group had more capillary dropouts and bizarre capillaries. Capillary dropouts, dilated capillaries, and visible subpapillary venous plexus were more prevalent in patients with Type 2 reactions. CONCLUSION: NFC changes are prevalent in both tuberculoid and lepromatous leprosy, which may be an indicator of peripheral vascular compromise and trophic changes, especially in lepromatous leprosy. NFC can be an auxiliary tool for detecting microvascular abnormalities in leprosy patients.

Cutaneous tuberculosis. Part I: Pathogenesis, classification, and clinical features.

Tuberculosis is an ancient disease that continues to affect an estimated 10 million people per year and is responsible for 1.4 million deaths per year. Additionally, the HIV epidemic and multidrug resistance present challenges to disease control. Cutaneous tuberculosis is an uncommon, often indolent, manifestation of mycobacterial infection that has a varied presentation. Its diagnosis is challenging, as lesions mimic other, more common conditions and microbiological confirmation is often not possible. Cutaneous tuberculosis can be broadly categorized into multibacillary and paucibacillary forms. Approximately one-third of skin tuberculosis is associated with systemic involvement. By recognizing cutaneous tuberculosis early, dermatologists can play an important role in disease control. The first article in this 2-part continuing medical education series describes the latest epidemiology, microbiology, and pathogenesis of tuberculosis. Furthermore, we review the classification, clinical manifestations, common clinical differentials, and systemic involvement that occur in cutaneous tuberculosis.

Cutaneous tuberculosis. Part II: Complications, diagnostic workup, histopathologic features, and treatment.

Despite the availability of effective treatment regimens for cutaneous tuberculosis, challenges to disease control result from delayed diagnosis, infection with multidrug-resistant mycobacterial strains, and coinfection with HIV. Delayed diagnosis can be mitigated when dermatologists are sensitized to the clinical signs and symptoms of infection and by the incorporation of appropriate diagnostic tests. All cases of cutaneous tuberculosis should be confirmed with histopathology and culture with or without molecular testing. In each case, a thorough evaluation for systemic involvement is necessary. Mycobacteria may not be isolated from cutaneous tuberculosis lesions and therefore, a trial of antituberculosis treatment may be required to confirm the diagnosis. The second article in this 2-part continuing medical education series describes the sequelae, histopathology, and treatment of tuberculosis.

Clinico-epidemiological profile and management outcome of subungual digital glomus tumor-Indian experience.

BACKGROUND: Glomus tumors are rare tumors arising from the mesenchymal smooth muscle cells of the glomus body. They are extremely painful tumors but because of their subungual location, remain mostly underdiagnosed. AIM: To characterize the demographic, clinical, onychoscopic, radiological features and management outcome of subungual glomus tumor. Material & methods- 15 patients with a total of 16 subungual glomus tumors were evaluated and their demographic data, history, clinical features, investigations, treatment, and follow-up were analyzed. RESULTS: Glomus tumors had a female preponderance (11/15) with thumb being the commonest site. All patients presented with intractable pain. Nail discoloration was observed in 11/16 (68.8%) lesions and nail plate deformity in 6/16 (37.5%) lesions. Common features on onychosocpy were pink glow and linear vascular structures. Doppler sonography and/or magnetic resonance imaging confirmed the diagnosis of glomus tumor in all the lesions. Surgical excision was done under local anesthesia using a trans-ungual approach and no recurrence was seen. CONCLUSIONS: High index of suspicion, meticulous clinical assessment along with radiological investigations can help in the early diagnosis. Complete surgical excision is the treatment of choice to prevent recurrence.

Nailfold capillary changes in newly diagnosed hypertensive patients: An observational analytical study.

INTRODUCTION: Nail Fold capillaroscopy (NFC) is used to evaluate microvascular changes in the horizontally lying capillaries in the proximal nail fold. Arterial hypertension affects the microvascular beds producing structural changes. Our objective was to evaluate qualitative and quantitative NFC changes in newly diagnosed hypertensives as compared to age and sex matched normotensive controls and to determine association, if any, with microvascular changes visualized on fundoscopy. MATERIALS AND METHODS: This observational, analytical study involved 41 newly diagnosed hypertensives (18-60 years) with 41 normotensive age and sex matched normotensive controls. The mean capillary density (MCD) and morphological changes were assessed for all, while fundoscopy was done for study group participants. The collected data was statistically analyzed. RESULTS: The MCD in newly diagnosed hypertensives (5.21 ± 0.90 capillaries/mm) was significantly lower than normotensive controls (6.50 ± 0.65 capillaries/mm) (p < 0.001) in our study. Qualitative morphologic changes were more common in hypertensive patients including meandering capillaries, capillary dilation, avascular areas, bushy capillaries, and microhemorrhages (p value <0.001). Capillary disarray (73.17%) was a unique morphologic change seen significantly more commonly in study group (p < 0.001). Among hypertensives, MCD was lesser in patients with retinopathy (p = 0.125) and with microalbuminuria, while avascular areas and dilated capillaries were significantly more common. CONCLUSION: Our study supports the role of NFC with USB dermatoscope in detecting unique microvascular morphological alterations in hypertensives, which were more frequent as well as distinctive, as compared to healthy controls. A good correlation with fundoscopic features and microalbuminuria suggests that it could be useful in predicting/detecting cardiovascular, or renal complications early, with an advantage of easy accessibility and repeatability.

Modulation of mRNA Expression of IL-6 and mTORC1 and Efficacy and Feasibility of an Integrated Approach Encompassing Cognitive Behavioral Therapy Along with Pregabalin for Management of Neuropathic Pain in Postherpetic Neuralgia: A Pilot Study.

OBJECTIVE: This study was designed to explore the efficacy and feasibility of cognitive behavioral therapy (CBT) along with pregabalin and compare it with pregabalin monotherapy for the management of neuropathic pain in post-herpetic neuralgia (PHN) patients and to explore the modulation of messenger RNA (mRNA) expression of interleukin (IL)-6 and mammalian target of rapamycin-1 (mTORC1) genes in these patients. DESIGN: Randomized controlled pilot study. METHODS: The patients aged >18 years of age with an established diagnosis of PHN with evident allodynia and hyperalgesia who had pain for at least 3 months after healing of rash with pain intensity ≥4/10 on NRS-Pain Scale were enrolled. The trial was registered with the Clinical Trials Registry-India (CTRI/2019/03/018014). A detailed baseline assessment regarding type and duration of pain and disability using pain-relevant self-report questionnaires was done. Two mL venous blood samples were collected for gene expression studies at base line and at end of 12 weeks of treatment. Patients were randomized into one of the two groups. Group PR received pregabalin and Group CP received CBT along with pregabalin. The pain intensity was measured using numeric rating scale (NRS)-Pain scale, neuropathic component of the pain by using Neuropathic Pain Symptom Inventory (NPSI) and Pain Detect Questionnaire (PDQ), sleep interference by NRS-Sleep, pain-related catastrophic thoughts by using Pain Catastrophizing Scale (PCS), depression and quality of life using Beck Depression Inventory-II (BDI-II) and Short Form-12 (SF-12), respectively. The research funding was supported by the intramural grant from the institution. RESULTS: A total of 40 patients with 20 in each group were included. Following integrated approach encompassing CBT and Pregabalin, group CP had significant downregulation of mRNA expression of IL-6; however, no such correlation was observed with mTOR expression. A significant decline in the intensity of pain, NPSI scoring for burning, allodynia, and pain-related catastrophizing were observed; also a significant improvement in depressive symptoms and quality of life were observed with the use of CBT. CONCLUSIONS: A significant downregulation of mRNA expression of IL-6 was observed; however, no significant correlation was observed between NRS pain score and ΔCt values of mRNA expression of both mTORC1 gene and IL-6 gene at baseline and at the end of 12th week. In addition, we note a significant decrease in pain intensity, depressive symptoms, and pain-related catastrophizing while improving QOL was observed with the use of CBT as a clinical adjunct along with pregabalin in PHN patients.

Clinico-mycological study of onychomycosis in a tertiary care hospital-A cross-sectional study.

Onychomycosis (OM), has a worldwide prevalence of 5% and 0.5%-5% in India. Trichophyton. rubrum (T rubrum) and T mentagrophytes are the most commonly isolated fungi. As the clinical and mycological characteristics change with time and geographical region; it is important to study the temporal and topographic patterns periodically. The study was conducted to identify the epidemiological and clinico-mycological characteristics of patients with OM attending a tertiary care hospital in Delhi. Hundred patients with clinical diagnosis of OM were recruited. Among these, 88 patients who tested positive for OM on direct microscopy with KOH, culture and/or histopathology with periodic acid-Schiff were included in the study. The clinico-mycological characteristics and risk factors associated with OM were evaluated. OM was more common in males (M:F = 2.5:1). The mean age of patients with OM was 39 ± 15.3 years (SE 1.52) with mean disease duration of 27.6 ± 46.1 months (SE 4.9). Seventeen (19.3%) patients had concomitant diabetes mellitus. The patients displayed mean body mass index (BMI) of 25.67 ± 1.35 kg/sq m. Concurrent dermatophytosis of skin was present in 35 (39.77%) patients. Two feet-one hand syndrome was present in 5 patients. Fingernail involvement without toenail involvement was more common than toenail involvement alone. (43.18% vs 38.63%). Distal and lateral subungual OM (DLSO) was the commonest clinical variant (81.8%). Mycological culture showed growth in 47 (53.40%) patients. Dermatophytes were isolated in majority, that is in 30 (63.82%) patients followed by non-dermatophytic moulds (NDM) in 7 (14.8%) and Candida spp. in the remaining 10 (21.27%) patients.

Indian Trichophyton mentagrophytes squalene epoxidase erg1 double mutants show high proportion of combined fluconazole and terbinafine resistance.

BACKGROUND: The Indian ITS genotype VIII Trichophyton mentagrophytes population shows a high amount of different erg1 (ergosterol) mutants encoding for squalene epoxidase, which catalyses the first step of ergosterol biosynthesis. OBJECTIVES: Illumination of the implication of point mutations at position Ala448Thr in single and double erg1 T mentagrophytes mutants because mutants of this type were abundantly found within the Indian fungal population. METHODS: Growth in fluconazole or terbinafine containing medium was analysed using a microplate-laser-nephelometry (MLN)-based growth assay. RESULTS: Ala 448 Thr erg1 single mutants were terbinafine sensitive, but about 50% of isolates showed an increased fluconazole resistance, whereas 95% of the double mutants (Phe 397 Leu, Ala 448Thr) demonstrated combined terbinafine and increased fluconazole resistance. CONCLUSION: The new Indian T mentagrophytes populations show several point mutations in erg1. Point mutations at position 397 were previously described and cause terbinafine resistance. A large part of the double mutants exhibit resistance to terbinafine and fluconazole, demonstrating a selective advantage of the combination of both mutations.

Alarming India-wide phenomenon of antifungal resistance in dermatophytes: A multicentre study.

BACKGROUND: An alarming increase in recalcitrant dermatophytosis has been witnessed in India over the past decade. Drug resistance may play a major role in this scenario. OBJECTIVES: The aim of the present study was to determine the prevalence of in vitro resistance to terbinafine, itraconazole and voriconazole in dermatophytes, and to identify underlying mutations in the fungal squalene epoxidase (SQLE) gene. PATIENTS/METHODS: We analysed skin samples from 402 patients originating from eight locations in India. Fungi were identified by microbiological and molecular methods, tested for antifungal susceptibility (terbinafine, itraconazole, voriconazole), and investigated for missense mutations in SQLE. RESULTS: Trichophyton (T.) mentagrophytes internal transcribed spacer (ITS) Type VIII was found in 314 (78%) samples. Eighteen (5%) samples harboured species identified up to the T interdigitale/mentagrophytes complex, and T rubrum was detected in 19 (5%) samples. 71% of isolates were resistant to terbinafine. The amino acid substitution Phe397Leu in the squalene epoxidase of resistant T mentagrophytes was highly prevalent (91%). Two novel substitutions in resistant Trichophyton strains, Ser395Pro and Ser443Pro, were discovered. The substitution Ala448Thr was found in terbinafine-sensitive and terbinafine-resistant isolates but was associated with increased MICs of itraconazole and voriconazole. CONCLUSIONS: The high frequencies of terbinafine resistance in dermatophytes are worrisome and demand monitoring and further research. Squalene epoxidase substitutions between Leu393 and Ser443 could serve as markers of resistance in the future.

Recommendations for the definition, evaluation, and treatment of nail psoriasis in adult patients with no or mild skin psoriasis: A dermatologist and nail expert group consensus.

Nail involvement in psoriasis is common, and the severity of it does not always parallel the intensity of cutaneous disease. We created a consensus group, of which the aim was to provide practical recommendations for the treatment of nail psoriasis in patients without skin psoriasis or with mild skin lesions with no indication for a systemic treatment. This collaborative process was conducted by an international panel of dermatologists with special expertise in nail disorders, using formal consensus methods. During this process, the panel strived to establish an agreement regarding the definition of nail psoriasis, the severity of nail psoriasis, and treatment response. Treatment recommendations are provided regarding nail psoriasis severity and matrix or bed involvement. Few-nail disease was considered as nail psoriasis affecting ≤3 nails. In the case of matrix involvement only, intralesional steroid injections were considered the treatment of choice. Topical steroids alone or in combination with topical vitamin D analogues were suggested for nail psoriasis limited to the nail bed. For the systemic treatment of nail psoriasis acitretin, methotrexate, cyclosporine, small molecules, and biologics may be employed.

Precalcaneal congenital fibrolipomatous hamartoma: Rare or under-reported?

Precalcaneal congenital fibrolipomatous hamartoma (PCFH) is a benign under-reported condition of infancy characterized by the presence of soft nodules on precalcaneal plantar surface of the heel. These lesions are usually bilateral solitary and asymptomatic. We present a 2-month-old infant with solitary skin-colored nodules present on precalcaneal plantar aspect of bilateral heels.

Clinical and histological spectrum of nail psoriasis: A cross-sectional study.

BACKGROUND: Nail psoriasis can pose diagnostic difficulties as there are several close clinical mimickers, including onychomycosis, lichen planus, and even squamous cell carcinoma. In view of differing treatment and prognostic implications, it is important to make an accurate diagnosis, especially in cases with isolated nail involvement. METHODS: Sixty consecutive patients with nail changes suggestive of psoriasis were included. A nail punch biopsy was performed and histopathological features were recorded for each case and percentage positivity of each individual feature was calculated. Periodic acid-Schiff (PAS) stain was performed to detect any fungal colonization or invasion. RESULTS: The most common clinical nail change was distal onycholysis (93.3% patients), followed by subungual hyperkeratosis (80%). On histological examination, the feature found most frequently was hyperkeratosis with parakeratosis (78% of biopsies), followed by neutrophilic infiltration of nail bed epithelium (63%), and hypergranulosis (58%). Unlike psoriasis elsewhere, nail bed and matrix histopathology revealed hypergranulosis in more than half of the cases. PAS stain was positive for fungal elements in 16 of 60 (26%) cases. CONCLUSION: This study provides a careful, detailed histopathological description of nail unit psoriasis in a large number of cases. The histopathologic features described, which are somewhat different from psoriasis elsewhere on the body, are of utility to pathologists who may receive nail biopsy specimens of hyperkeratotic lesions.

Phacomatosis pigmentovascularis type 2b (phacomatosis cesioflammea) with double superior vena cava, abdominal varicosities, and natal tooth: Novel associations.

Phacomatosis pigmentovascularis is characterized by coexistent extensive cutaneous vascular (capillary) and pigmentary anomalies. We describe a 2-month-old infant presenting with classic features of phacomatosis pigmentovascularis 2b (phacomatosis cesioflammea). He was also found to have hitherto unreported associations in the form of extensive venous anomalies presenting as striking abdominal wall varicosities and persistent left superior vena cava and natal tooth.

Dyslipidaemia & oxidative stress in patients of psoriasis: Emerging cardiovascular risk factors.

BACKGROUND & OBJECTIVES: Psoriasis is a recurrent hyper-proliferative skin disease which is often associated with free radical generation, abnormal lipid metabolism and increased inflammatory secretion that induce cardiovascular risk in these patients. The present study was intended to evaluate serum lipids, lipoprotein and oxidants-antioxidants status and to establish their relationship with atherogenic risk markers [oxidized low-density lipoprotein (oxLDL) and high-sensitivity C-reactive protein (hsCRP)] in patients with psoriasis. METHODS: The study was conducted on 150 psoriasis patients and 150 age- and sex-matched healthy controls. Overnight fasting blood samples were obtained for lipids, lipoproteins, lipid oxidation and peroxidation products [oxLDL, malondialdehyde (MDA)], antioxidant enzymes [reduced glutathione (GSH) and total antioxidant status] levels and hsCRP estimations. RESULTS: The mean levels of atherogenic lipids [total cholesterol (P<0.001), triacylglycerol (P<0.01)], lipid peroxidation products (P<0.001) and oxLDL and hsCRP (P<0.001) levels in patients with psoriasis were found to be significantly higher than those of healthy controls. On the other hand, ferric-reducing ability of plasma (FRAP, P<0.001) and antioxidant enzyme activities (reduced GSH, P<0.01) were significantly lower when compared to healthy controls. The plasma oxLDL was positively correlated to LDL cholesterol (P<0.001) and MDA (P<0.001) and negatively associated with antioxidant status in these patients. Serum MDA, FRAP and oxLDL were correlated with risk of atherosclerosis in the patients with psoriasis; however, no significant association was found between reduced GSH and hsCRP. INTERPRETATION & CONCLUSIONS: The study results suggest that LDL oxidation and reactive oxygen species in addition to inflammatory markers may play a pivotal role in inducing atherosclerosis in patients of psoriasis.

BCG vaccine for immunotherapy in warts: is it really safe in a tuberculosis endemic area?

Management of recurrent and or recalcitrant warts can be a therapeutic challenge and in such cases invoking body's own immunity may help to overcome the present episode and also prevent recurrences. Bacilli Calmette Geurin (BCG) immunotherapy has long been considered to be an effective and safe modality in such cases. We present a series of seven cases treated with BCG immunotherapy wherein a single dose of BCG caused regression of wart in 85.7% patients and complete resolution was evident in 28.6% patients. However, the development of adverse effects precluded any further dosages in four of seven (57.1%) patients. This raises serious concern on the safety of this therapeutic modality, especially in a population endemic to tuberculosis.