Management of pain in the inpatient and non-surgical outpatient dermatology settings: A narrative review.

Pain is frequently encountered in dermatology practice, which impairs the activities of daily living, adds to psychological morbidity, and therefore compromises the quality of life. It ranges from mild to severe in intensity across various dermatoses and requires prompt addressal and treatment. Diseases such as extensive pemphigus vulgaris and Stevens-Johnson syndrome are especially painful and require a multidisciplinary approach with the involvement of a pain specialist in their management. The main pathogenic types of pain include visceral nociceptive, somatic nociceptive, and neuropathic types, the latter two being most relevant in dermatological disorders. Somatic nociceptive pain is often seen in patients of Stevens-Johnson syndrome/ Toxic epidermal necrolysis, epidermolysis bullosa, pemphigus vulgaris, erythema nodosum, and hidradenitis suppurativa, while neuropathic pain is part of the disease process in dermatoses like leprosy, herpes zoster, and dysesthesia syndromes. Therapeutic approaches to pain management include the use of non-opioids (acetaminophen, non-steroidal anti-inflammatory agents), opioids, and non-pharmacological therapies, along with appropriate management of the underlying dermatosis. World Health Organisation (WHO) analgesic ladder remains the most commonly employed guideline for the management of pain, although treatment needs individualisation depending on the nature and severity of pain (acute/chronic), type of dermatosis, and patient factors. There is a paucity of literature pertaining to pain management in dermatology and this topic is often neglected due to a lack of awareness and knowledge of the topic. The present review aims to discuss the pain pathway, various painful conditions in the setting of medical dermatology practice, and their management along with relevant pharmacology of the commonly used analgesics.

Prolonged treatment of dermatophytosis caused by Trichophyton indotinea with terbinafine or itraconazole impacts better outcomes irrespective of mutation in the squalene epoxidase gene.

BACKGROUND: Over the past decades, the increasing incidence of recurrent dermatophytosis associated with terbinafine-resistant Trichophyton has posed a serious challenge in management of dermatophytosis. Independent reports of failure of treatment and high minimum inhibitory concentrations (MIC) of antifungals are available, but data correlating MIC and clinical outcomes is still sparse. Therefore, the present study was conducted to evaluate the outcomes of systemic treatment of dermatophytosis and its correlation with MIC of the etiological agents isolated from such patients. METHODS: Retrospective analysis of 587 consecutive patients with dermatophytosis was done from March 2017 to March 2019. Demographic and clinical details of the patients were noted, along with the results of direct microscopy and fungal culture. The isolates were identified by sequencing the internal transcribed spacer region of rDNA. Antifungal susceptibility testing was performed following the CLSI M38 protocol. Mutation in the squalene epoxidase (SE) gene was detected by DNA sequencing and ARMS-PCR. Based on the culture-positivity and prescribed systemic antifungal, patients were categorised into Group I culture-positive cases treated with systemic terbinafine and Group II culture-positive cases treated with systemic itraconazole, each for a total period of 12 weeks. RESULTS: In the present study, 477 (81.39%) were culture-positive; however, 12 weeks follow-up was available for 294 patients (Group I-157 and Group II-137) who were included for statistical analysis. In both groups [Group I-37/63 (51.4%) and Group II-14/54 (58.3%)], a better cure rate was observed if the initiation of therapy was performed within <6 months of illness. Treatment outcome revealed that if therapy was extended for 8-12 weeks, the odds of cure rate are significantly better (p < .001) with either itraconazole (Odd Ratio-15.5) or terbinafine (Odd Ratio-4.34). Higher MICs for terbinafine were noted in 41 cases (cured-18 and uncured-23) in Group I and 39 cases (cured-16 and uncured-23) in Group II. From cured (Group I-17/18; 94.4% and Group II-14/16; 87.5%) and uncured (Group I-20/23; 86.9% and Group II-21/23; 91.3%) cases had F397L mutation in the SE gene. No significant difference in cure rate was observed in patients with Trichophyton spp. having terbinafine MIC ≥ 1or <1 µg/mL (Group I-p = .712 and Group II-p = .69). CONCLUSION: This study revealed that prolonging terbinafine or itraconazole therapy for beyond 8 weeks rather than the standard 4 weeks significantly increases the cure rate. Moreover, no correlation has been observed between antifungal susceptibility and clinical outcomes. The MIC remains the primary parameter for defining antifungal activity and predicting the potency of antifungal agents against specific fungi. However, predicting therapeutic success based solely on the MIC of a fungal strain is not always reliable, as studies have shown a poor correlation between in vitro data and in vivo outcomes. To address this issue, further correlation of antifungal susceptibility testing (AFST) data with clinical outcomes and therapeutic drug monitoring is needed. It also highlights that initiation of the treatment within <6 months of illness increases cure rates and reduces recurrence. Extensive research is warranted to establish a better treatment regime for dermatophytosis.

Clinico- Therapeutic Study of Stevens Johnson Syndrome-Toxic Epidermal Necrolysis and Prognostic Significance of SCORTEN in Indian Patients.

Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) are life-threatening dermatological emergencies. SCORTEN (SCORe of toxic epidermal necrolysis) is a validated score to predict mortality; however, there is a paucity of data to determine its usefulness in the Indian population. Objective: To evaluate the accuracy of SCORTEN as a prognostic marker in SJS-TEN. Methods: A prospective observational study was conducted at a tertiary care hospital for two years. SCORTEN was calculated on days one and three of admission. The actual death rates were compared to the predicted rates as estimated by the SCORTEN by standardised mortality ratio analysis (SMR). Results: Of 40 cases included in the study, the mean age was 36.2 ± 14 years (range 11-65) with the male: female ratio being 1.67:1. Antibiotics (37.5%) were the most common group followed by anticonvulsants (22.5%). Comorbidities were observed in 60% of cases, with epilepsy (17.5%) and HIV (human immunodeficiency virus) infection (12.5%) being common. On univariate analysis, heart rate > 120/min, epidermal detachment > 10% BSA, and Se HCO3 (bicarbonate) <20 mmol/L were associated significantly with the death of the subjects (P < 0.05). The observed mortalities were 4.34%, 0, 0 and 80% for SCORTEN 0-1 (3.2%), 2 (12.1%), 3 (35.8%) and 4 (58.3%) respectively when compared to expected mortality. SMR of SJS was 0.69 and of TEN was 1.49. Conclusion: SCORTEN gave an overestimation of mortality in patients with lower scores and an underestimation of mortality in patients with higher scores in our study. Minor refinements based on the study population may increase the predictive accuracy of the original scale.

Acquired dermal macular hyperpigmentation: an overview of the recent updates.

Acquired dermal macular hyperpigmentation (ADMH), previously known as macular pigmentation of uncertain etiology (MPUE), is an umbrella concept that unifies the distinct but overlapping acquired dermal pigmentary disorders like lichen planus pigmentosus, ashy dermatosis, erythema dyschromicum perstans, Riehl's melanosis and pigmented contact dermatitis. All of these disorders usually lack a clinically apparent inflammatory phase, are characterised by dermal pigmentation clinically and histologically, and have a variable protracted disease course. Recently, a proposal has been made to classify these disorders into those with and without contact sensitisation. Dermoscopy is essentially similar across the spectrum of these disorders, and is useful for diagnosis and therapeutic response monitoring. Scoring system has been validated for the same. The treatment of ADMH remains challenging, with multiple topicals, oral therapies including mycophenolate mofetil, and lasers tried. Need of the hour is randomised controlled trials to enhance the therapeutic armamentarium.

A Comparative Study on Therapeutic Efficacy of Autologous Platelet-rich Plasma, Autologous Platelet-rich Fibrin Matrix, Recombinant Human Epidermal Growth Factor, and Collagen Particles in Nonhealing Leg Ulcers.

Background: Nonhealing leg ulcers are challenging to manage and cause significant patient morbidity. To promote healing, newer techniques focus on delivering/enhancing dermal matrix components. Aim: The aim of this study was to compare the therapeutic efficacy of autologous platelet-rich plasma (PRP), autologous platelet-rich fibrin matrix (PRFM), recombinant human epidermal growth factor (rhEGF), and collagen particles in treating nonhealing leg ulcers. Materials and Methods: Open, randomized prospective study was conducted in a single tertiary center over 2 years where after fulfilling the criteria, randomization was done into four groups. Group A: Autologous PRP (double spin, manual method, weekly); Group B: Autologous PRFM (weekly); Group C: rhEGF (daily application); and Group D: Collagen particles (weekly) along with cleansing, debris removal, and wound dressing. Treatment endpoints were complete healing/6 months of treatment, whichever was earlier. Follow-up was done two weekly by clinical assessment, photographs, and measurement of the ulcer area. Epi info 7 software was used for statistical analysis. Results: A total of 48 patients completed the study, 12 in each group, with mean age: 42.37 ± 4.56 years and male-to-female ratio 2.6:1. Underlying etiology was varicosities (43.75%), traumatic (25%), diabetes (22.91%), and leprosy (8.34%). At baseline, all groups were comparable in terms of patient and ulcer characteristics. Complete healing was seen in 79.17% at the end of 12 weeks: 91.67% of patients from Groups A and B each, and 66.67% from Groups C and D each. The mean time to complete healing was 6.9 ± 2.5 weeks, the least in Group B (4.73 ± 2.3 weeks). Differences between excellent (≥75%) ulcer healing across all groups were statistically significant at the end of 8 weeks where Group B showed maximum improvement. No major adverse events were seen. Conclusion: PRFM resulted in relatively faster ulcer healing compared with other modalities.

A single-centre prospective study comparing efficacy and safety of apremilast with cyclosporine in moderate to severe atopic dermatitis.

BACKGROUND: Apremilast regulates several pro-inflammatory signals involved in atopic dermatitis (AD). METHODS: A randomized, open-labelled study was conducted at a tertiary care centre in India. Fifty patients with AD of >1 year duration were randomly assigned in a 1:1 ratio to receive either apremilast (30 mg twice daily after initial titration) or cyclosporine (5 mg/kg/day) for 24 weeks, followed by a 12-week follow-up period. Primary outcome was mean percentage change in Eczema Area and Severity Index (EASI) from baseline to week 24. Secondary outcome measures were proportion of patients achieving EASI 75, EASI 90, ≥2-point improvement in Investigator's Global Assessment (IGA), SCORing Atopic Dermatitis (SCORAD) 75 at week 24 and percentage of patients experiencing ≥1 adverse effect (AEs). RESULTS: Mean percentage change in EASI (standard deviation) was -67.79% [22.44] in the apremilast treatment group and -83.06% [21.20] in the cyclosporine treatment group (p < 0.05). At week 24, 52.38% of patients in the apremilast group and 78.26% in the cyclosporine group achieved EASI 75 (p < 0.05); 14.29% in the apremilast group and 52.17% in the cyclosporine group achieved EASI 90 (p < 0.05) and 80.95% in the apremilast group and 82.60% patients achieved ≥2 point reduction in IGA (p > 0.05). 57.14% of patients achieved SCORAD 75 in the apremilast group and 69.56% in the cyclosporine group (p > 0.05). Mean time taken to achieve EASI 75 in the apremilast group was 4.50 ± 4.62 weeks, while it was 3.96 ± 3.43 weeks in the cyclosporine group (p > 0.05). Incidence of AEs was 28.57% in the apremilast group and 21.74%) in the cyclosporine group. CONCLUSIONS: Apremilast demonstrated lesser efficacy in comparison to cyclosporine; it has the advantage of a favourable safety profile and requires no laboratory monitoring.

A Clinical-Mycological Study of Dermatophytosis in Western India with Focus on Antifungal Drug Resistance as a Factor in Recalcitrance.

Background: Dermatophytosis have assumed epidemic proportions in India. Antifungal drug resistance solely cannot explain disease magnitude and changing epidemiology. Objectives: Aim of this study was to analyse clinical-mycological aspects of dermatophytosis, and estimate contribution of drug resistance in clinical recalcitrance. Methods: This single-centre observational, cross-sectional, descriptive study was done in tertiary centre of western India after ethical approval, enrolling dermatophytosis patients of all ages and sex. After history and examination, KOH mount and culture in modified SDA medium was done. Culture positive isolates were subjected to E-strip antifungal susceptibility method to test MIC for Terbinafine, Itraconazole, Fluconazole and Griseofulvin. Results: Total 300 patients were included, with mean age of 33.83±27.5 years and male-to-female ratio of 1.22:1; tinea corporis et cruris being commonest, 39.33% (n=118). Only 11.67% (n=35) were treatment naïve, having classical annular morphology. History of topical steroid abuse was found in 81.67% (n=245), with pseudoimbricate lesions in 70.61% (n=173). 86.67% (n=260) had KOH positivity while 83.33% (n=250) had culture positivity: Trichophyton mentagrophytes 45.6% (n=114), followed by Trichophyton rubrum in 34.4% (n=86). A total of 265 patients fit into definition of recalcitrance, from which 12.45%, i.e., 33 isolates showed in-vitro fluconazole resistance. 14.33% (n=43) cases were chronic, 37% (n=111) persistent, 46% (n=138) recurrent while 17% (n=51) had relapse in their disease course. Steroid abuse was the commonest denominator. Conclusion: Role of antifungal resistance in recalcitrant dermatophytosis remains debatable. Stopping steroid abuse, which is often the commonest culprit, with adherence to standard antifungal therapy remains the paradigm in management.

Emerging Role of Baricitinib in Dermatology Practice: All We Need to Know!

Baricitinib is a competitive inhibitor of the Janus Kinase family of non-receptor protein kinases, predominantly acting against JAK-1 and JAK-2 subtypes. By downregulating transcription of various pro-inflammatory cytokines, this drug has shown efficacy across various dermatoses. Approved for severe cases of alopecia areata and moderate-severe atopic dermatitis in adults, baricitinib is being increasingly tried across many other indications with promising results. It is prudent that dermatologists remain aware of boxed warnings and precautions with the use of this much-discussed molecule, including its infectious, thrombotic, cardiovascular, and malignant ramifications. Long-term data on the use of baricitinib in dermatological conditions are lacking and further research is warranted since most data on safety profile is extrapolated from its use in rheumatology. The present review aims to highlight the immunopathogenic mechanisms of JAK-1/2 blockade, approved and off-label uses in dermatology, along with a concise review of laboratory monitoring and the side-effect profile of baricitinib.