T helper type 1 polarizing γδ T cells and Scavenger receptors contribute to the pathogenesis of Pemphigus vulgaris.

γδ T cells and Scavenger receptors are key parts of the innate immune machinery, playing significant roles in regulating immune homeostasis at the epithelial surface. The roles of these immune components are not yet characterized for the autoimmune skin disorder Pemphigus vulgaris (PV). Phenotyping and frequency of γδ T cells estimated by flow cytometry have shown increased frequency of γδ T cells (6·7% versus 4·4%) producing interferon- γ (IFN-γ; 35·2% versus 26·68%) in the circulation of patients compared with controls. Dual cytokine-secreting (IFN-γ and interleukin-4) γδ T cells indicate the plasticity of these cells. The γδ T cells of patients with PV have shown higher cytotoxic potential and the higher frequency of γδ T cells producing IFN-γ shows T helper type 1 polarization. The increased expression of Scavenger receptors expression (CD36 and CD163) could be contributing to the elevated inflammatory environment and immune imbalance in this disease. Targeting the inflammatory γδ T cells and Scavenger receptors may pave the way for novel therapeutics.

Utility of Horizontal Sections of Scalp Biopsies in Differentiating between Androgenetic Alopecia and Alopecia Areata.

BACKGROUND: Androgenetic alopecia (AGA) and alopecia areata (AA) are common causes of alopecia which can sometimes be difficult to differentiate clinically. Horizontal sections of scalp biopsies are used to study non-cicatricial alopecias due to the ability to perform both quantitative and morphometric analysis of hair follicles on them. METHODS: It was a prospective, cross-sectional study conducted to assess the utility of horizontal sections to differentiate between the alopecias. Fifty-two cases were included: 20 cases of male AGA, 11 of female AGA and 21 cases of AA. After clinical examination and dermoscopy, a skin biopsy was taken and subjected to transverse sectioning. Histopathological assessment was done by two dermatopathologists blinded to clinical details. RESULTS: Among the quantitative parameters, terminal:vellus hair ratio (3.08 in AGA and 1.83 in AA, p = 0.0091) and anagen:non-anagen hair ratio (9.25 in AGA and 3.56 in AA, p = 0.0021) were significantly lower in AA. In qualitative parameters, peribulbar inflammation was seen in 63% of AA cases (p = 0.0001). Pigment casts were seen in twice the number of AA (57%) than AGA (26%) cases. Broad avascular stelae and focal trichomalacia were seen in 9.5% of AA cases. CONCLUSION: Besides peribulbar inflammation, we found a lower anagen:non-anagen hair ratio and presence of pigment casts in transverse sections of scalp biopsies favouring AA over AGA.

Assessment of histopathological features of maculopapular viral exanthem and drug-induced exanthem.

BACKGROUND: Viral infections and drug reactions are the commonest causes of exanthems in clinical practice. Clinically, their overlapping features may pose a diagnostic challenge. Hematologic, in vitro, and drug provocation tests are either unreliable or impractical. METHODS: This was a descriptive, prospective study to assess and compare histopathological features of maculopapular viral and drug exanthem. Subjects fulfilling case definition of exanthems were included. Serum C-reactive protein (CRP) and absolute eosinophil count (AEC) were also studied. RESULTS: Skin biopsy slides of 48 cases were evaluated and AEC and CRP were performed. Both median AEC and CRP were lower in viral exanthem compared with drug exanthem. On histopathological evaluation, features such as lymphocytic exocytosis, and dermal infiltrate of eosinophils, lymphocytes and histiocytes were seen in a significantly greater number of drug exanthems. Other findings such as focal spongiosis, acanthosis, keratinocyte necrosis, basal cell damage, papillary dermal edema and atypical lymphocytes in the dermis were also observed in higher though not statistically significant number of drug exanthem biopsies. CONCLUSIONS: Certain histopathological features can help to differentiate between the two exanthems and this modality may be used in situations when there is clinical overlap and when drug rechallenge cannot be undertaken.

Assessment of Efficacy of the 595-nm Pulsed Dye Laser in the Treatment of Facial Port-Wine Stains in Indian Patients.

BACKGROUND: Pulsed dye lasers have revolutionized treatment of port-wine stains (PWS). The authors' previous study with a 585-nm/0.45-millisecond pulsed dye laser (PDL) showed 25% to 75% improvement in 60% of facial PWS. METHODS: The authors analyzed data on facial PWS treated with a 595-nm tunable PDL in Indian patients. Response was assessed subjectively on a scale of -1 to 5 (Investigator Global Assessment) by comparing pretreatment and posttreatment photographs. Patients' perception of change in PWS was also noted on a visual analog scale from 0 to 10 (Patient Global Assessment). Side effects were recorded. RESULTS: A total of 74 flat and 24 hypertrophic PWS in skin Types IV and V with a median lesion size of 56 cm and 102 cm, respectively, and color ranging from pink to purple were treated. They underwent a mean of 7.3 and 8.5 sessions (range: 4-10 session), respectively. A mean lightening of 54% in flat and 40% in hypertrophic PWS was observed. After 10 treatments, 46.6% of flat PWS cases showed >75% lightening and an equal number had 25% to 75% improvement. A >75% improvement was observed in 12.5% of hypertrophic PWS with 75% of cases showing between 25% to 75% improvement. No significant side effects were noted. CONCLUSION: The 595-nm tunable PDL produced moderate response with no significant side effects.

Inflammatory leg nodules: A clinical and investigational study.

BACKGROUND: Inflammatory leg nodules are a diagnostically challenging group of dermatoses with limited tools for diagnosis. Considerable overlapping patterns exist despite their distinct clinical and histological features. We attempted to understand if undertaking investigations and studying the clinical course and treatment response can help in differentiating these dermatoses. METHODS: Forty-three patients presenting with inflammatory leg nodules underwent a series of investigations apart from histopathology. The patients were treated as per the final histological diagnosis and observed for response to treatment and followed up to evaluate the clinical course. RESULTS: There was considerable overlap in the investigations done among various dermatoses. These included elevated erythrocyte sedimentation rate (ESR), Mantoux test and antistreptolysin- O (ASLO) titres in the majority of patients while a few had abnormal findings on chest X-ray, CT scan of the chest and doppler ultrasonography of the legs. About 86% of patients with erythema nodosum, 50% with erythema induratum, 57% with cutaneous medium vessel vasculitis and 93% with unclassified panniculitis responded to non-steroidal non-inflammatory drugs (NSAIDs) alone or had spontaneously resolved with only post-inflammatory hyperpigmentation. Other patients required specific treatment with immunosuppressive or immunomodulatory agents. CONCLUSIONS: There is considerable overlap in dermatoses manifesting as inflammatory leg nodules on investigations, treatment received and response to treatment. To categorize them better into distinct entities, this group of dermatoses may require long-term follow-up of the clinical course and response to treatment, repeated investigations especially histopathology during different phases of evolution and progression of disease.

Xanthoma disseminatum associated with inflammatory arthritis and synovitis--a rare association.

Xanthoma disseminatum (XD) is a rare, benign, non-Langerhans cell histiocytosis characterized by disseminated xanthomatous lesions with a predilection for the face, flexures, and mucosae. Approximately 100 cases have been reported in the literature. We report XD in an 8-year-old boy with symmetric synovitis and arthritis involving the wrists and knees. This case is interesting in view of the association between arthritis and synovitis and XD, which to our knowledge has not been reported in the literature. This case has to be differentiated from multicentric histiocytosis, another non-Langerhans cell histiocytosis, in which joint involvement is common.

Dominance and improved survivability of human γδT17 cell subset aggravates the immunopathogenesis of pemphigus vulgaris.

Human γδ T cells are highly enriched in epithelial cell-dominated compartments like skin. Nonetheless, their function in the pathogenesis of pemphigus vulgaris (PV), an autoimmune skin disorder, is lacking. Therefore, we investigated the functional expression of human γδT cell subsets along with their homing chemokine receptor-ligand and inflammatory cytokines in the immunopathogenesis of PV. Estimation of the frequency of γδT cell subsets by flow cytometry revealed four major subsets of γδ T cells (γδT1, γδT2, γδT17, γδTreg) in both control and PV circulation. The elevated frequency of γδT17 cells producing IL17 and expressing CCR6 receptor suggests their inflammatory and migratory potential in PV. In vitro culture of γδ T cells from patients showed increased mRNA expression of inflammatory cytokines IL17, RORγt, IL23, IL1, and co-stimulatory markers, CD27 and CD70. These findings correlated the role of IL1 and IL23 cytokines that alleviate the Th17 population in PV. Cytotoxic activities of γδ T cells were higher and inflammatory γδT17 cells were localized in the skin of PV whereas γδTreg cells associated TGFß and FOXP3 were lowered. Hyperinflammatory phenotype of the γδT17 cell subset and its migratory potential might be aiding in the pathogenesis of PV, whereas γδTreg cells fail to suppress these inflammatory responses. Hence, γδT17 cell-associated markers can be targeted for identifying novel therapeutics in PV.

Comparison of the Clinical Efficacy of Rituximab Infusion and Dexamethasone-Cyclophosphamide Pulse Therapy and Their Effect on Serum Th1, Th2, and Th17 Cytokines in Pemphigus Vulgaris-A Prospective, Nonrandomized, Comparative Pilot Study.

Background: Rituximab infusion and dexamethasone-cyclophosphamide pulse (DCP) are the two most popular regimens used in pemphigus vulgaris (PV) in India. Objective: The present study compared the clinical efficacy of rituximab and DCP in Indian PV patients and their effects on serum Th1,2, and 17 cytokine levels. Materials and Methods: A total of 37 patients received DCP (Group A, n = 22) or rituximab (Group B, rheumatoid arthritis protocol (n = 15)) as per patients' preference. They were monitored for clinical response, adverse events (AEs), changes in serum anti-desmoglein-1,3 antibody titers and Th1,2 and 17 cytokine levels at baseline and weeks 20 and 52. Results: The proportion of patients attaining disease control, remission, and relapse in groups A and B were 82% and 93%; 73% and 93%; and 27% and 50%, respectively, after a median duration of 2 months each for disease control; 4 and 4.5 months for remission; and 5 and 7 months for relapse post remission. The musculoskeletal AEs were the highest in the two groups. Significant and comparable decreases in anti-dsg1 and 3 titers from baseline to weeks 20 and 52 were observed in both groups. Th1 and Th17 cytokine levels decreased, while Th2 cytokines increased post-treatment in both groups. However, no correlation was found between change in body surface area of involvement by PV and anti-dsg titers and cytokine levels before and after therapy in both groups. Conclusion: Comparable clinical efficacy between DCP and rituximab was observed.

Clinical and immunological predictors of post-rituximab paradoxical pemphigus flare: A prospective cohort study.

Background Paradoxical flare of pemphigus following rituximab infusion has been reported previously, however, its incidence or risk factors have not been studied in detail. Objectives To evaluate the clinical and immunological predictors associated with post-rituximab paradoxical pemphigus flare. Materials and Methods This was a prospective cohort study including adult patients with pemphigus vulgaris or foliaceus who were treated with rituximab. Patients were administered 1000 mg of intravenous rituximab on days 0 and 14 (Rheumatoid arthritis (RA) protocol), with or without oral prednisolone and/or conventional immunosuppressive agents. Baseline clinical and immunological predictors of post-rituximab pemphigus flares were assessed. Results Fifty patients (mean age 40.44 ± 12.36 years) with a mean pemphigus disease area index (PDAI) score of 27.8 ± 15.48 were administered rituximab. Post-rituximab flare occurred in 10 (20%) patients after a mean of 14.1 ± 4.33 days after the first rituximab infusion. The mean baseline PDAI score (36.4 ± 11.7 vs. 25.6 ± 15.7, P = 0.02) and serum anti-Dsg1 levels (1216.8 ± 850.1 vs. 592 ± 562.12 RU/mL, P = 0.03) were statistically significantly higher in patients experiencing a flare. Using ROC-curve analysis, a PDAI score of 328 (OR 8.3, 95% CI 1.5-44.7) was 80% sensitive and 67.5% specific in predicting post-rituximab flare, while serum anti-Dsg1 level of 31137.78 RU/ml had a sensitivity of 60% and specificity of 85%. There was no significant difference in terms of affected body surface area, type of pemphigus, starting prednisolone dose, oral immunosuppressive adjuvant, serum anti-Dsg3, serum anti-AchRM3, and peripheral CD19+ B cell population. Limitations Our study is limited by a relatively small sample size. Immunological factors were not evaluated at the time of pemphigus flare. Though these unexpected pemphigus flares are likely to be associated with rituximab infusion, the possibility of spontaneous disease exacerbation cannot be entirely excluded. Conclusions Patients with more severe pemphigus or high serum anti-Dsg1 are at risk of post-rituximab paradoxical flare, and may benefit from rituximab administration under close monitoring.

An Open-Label Non-Randomized Preliminary Noninferiority Study Comparing Home-Based Handheld Narrow-Band UVB Comb Device with Standard Hospital-Based Whole-Body Narrow-Band UVB Therapy in Localized Vitiligo.

Background: Narrow-band ultraviolet B (NB-UVB) is the standard therapy for vitiligo. Objective: The objective of this study is to compare the safety and clinical efficacy of a handheld NB-UVB comb device with the standard whole-body NB-UVB therapy in localized stable vitiligo. Materials and Methods: Thirty-one vitiligo patients were allocated to either daily therapy with a home-based handheld comb device (group A, n = 17) or thrice-weekly hospital-based whole-body NB-UVB therapy (group B, n = 14) for 4 months, based on their preference. The primary and secondary outcomes were assessed at each follow-up, and appropriate statistical tools were used for analysis. Results: Of the 31 patients enrolled, 26 patients (study groups A/B: 15/11) completed the study. Primary outcome: Median percentage repigmentation of the representative patch in groups A and B were 51.35% and 63.85%, respectively (P = 0.64). The median size reduction of the representative patch in both groups was statistically significant (P < 0.05). The mean difference between "per protocol analysis" and "intention to treat" showed noninferiority. Secondary outcomes: Both groups were comparable on Lund and Browder score, patient global assessment and investigator global assessment scores, adverse events, color match, and change in the quality of life. The comparison group had a significantly greater number of missed sessions (P = 0.02). The majority of patients had a "good" response in both groups. Conclusion: Handheld NB-UVB comb device daily with a fixed dose of fluence was found to be noninferior with better compliance to standard whole-body NB-UVB therapy.

Current understanding of frictional dermatoses: A review.

Human skin is continually exposed to internal and external forces, dynamic as well as static. The skin is normally flexible and can resist mechanical trauma due to friction, pressure, vibration, suction and laceration to a considerable degree. However, an excess of these forces can abnormally affect the structure and function of the skin, setting the stage for the development of a skin disorder. Repetitive trauma can cause lichenification, hyperpigmentation, erythema, scaling, fissuring, blisters, ulceration and chronic alterations. Frictional dermatoses is an under-recognised entity with no clear-cut definition and encompasses a variety of terms such as frictional dermatitis, frictional melanosis, frictional pigmentary dermatoses and certain other named entities, many of which are confusing. The authors propose to define frictional dermatoses as 'a group of disorders caused by repetitive trauma to the skin as a result of friction of varied aetiology which can have a wide range of cutaneous manifestations depending on the type of insult.' The exact prevalence of frictional dermatoses as a separate entity is unknown. Authors who conducted this review include a group of dermatologists and post graduate students from various institutions. Literature was reviewed through PubMed, Medscape, Medline, ResearchGate and Google Scholar using the terms 'frictional dermatitis,' 'friction and skin,' 'dermatoses and culture,' 'clothing dermatitis,' 'friction melanosis,' 'PPE induced dermatoses in COVID-19 era,' etc. A total of 122 articles were reviewed and 100 articles among them were shortlisted and included in the study, after removing duplications. The review was followed up with further deliberation which resulted in the formulation of a new definition and classification of frictional dermatoses taking into account the morphology, histopathological characteristics, anatomical region affected and the major predisposing factors. The rising incidence of mechanical dermatoses in the COVID-19 era was also emphasised.

Drug-Induced vs. Viral Maculopapular Exanthem-Resolving the Dilemma.

Maculopapular exanthem is a commonly encountered presentation in routine clinical practice, and differentiation between its two most common etiologies, i.e., viral- and drug-induced, often poses a diagnostic dilemma. Clinical, hematological and biochemical investigations are seldom reliable in distinguishing between a drug reaction and a viral exanthem. Certain key histopathological features such as the presence of a moderate degree of spongiosis, extensive basal cell damage with multiple necrotic keratinocytes and dermal infiltrate rich in eosinophils or lymphocytes and histiocytes may favor a drug exanthem, while distinctive epidermal cytopathic changes and lymphocytic vasculitis point towards a viral etiology. Similarly, notable immunohistochemical markers such as IL-5, eotaxin and FAS ligand may support a diagnosis of a drug-induced maculopapular eruption. Histopathological and immunohistochemical evaluations may help in distinguishing between the two etiologies when faced with a clinical overlap, especially in patients on multiple essential drugs when drug withdrawal and rechallenge is not feasible.

Patient perception and satisfaction with a smartphone-based teledermatology service initiated during the COVID-19 pandemic at a tertiary care hospital in North India.

Background Telemedicine is being increasingly used to provide healthcare to patients, particularly during the COVID-19 pandemic. Aims The study aimed to study patient perception and satisfaction with a smartphone-based hybrid teledermatology service initiated during the COVID-19 pandemic. Methods This was a cross-sectional telephonic survey including patients ≥18 years of age who had received a teledermatology consultation. After noting the demographic, clinical and teleconsultation details, patients were administered the Telemedicine Satisfaction Questionnaire and an additional 6-item questionnaire. Patients were also asked to give qualitative feedback and suggestions for improvement using a semi-structured interview guide. Results We interviewed 201 subjects. The most common diagnoses were pemphigus (27, 13.4%), superficial fungal infections (24, 11.8%), psoriasis (22, 10.9%) and dermatitis (21, 10.4%). The overall mean Telemedicine Satisfaction Questionnaire score was 4.20± 0.71. One hundred seventy-one (85.1%) patients responded that they would use teledermatology services again, while 168 (83.6%) reported satisfaction with the quality of services. A majority of the patients were largely satisfied with the various components involved, though some concerns were raised about the care perceived as not at par with physical consultations, difficulty in procuring medicines, lack of confidence in photographic diagnoses and the lack of a personal touch. Patients with urticaria (P=0.020), those who were advised a change in treatment (P=0.029) and those with improvement in their skin disease (P=0.026) were more likely to be satisfied. Limitations Our study was conducted during the COVID-19 pandemic when patient acceptability was likely to be higher. Only follow-up patients were included in the study. Conclusion Patient satisfaction levels were generally high with teledermatology. Addressing lacunae that negatively impact patient perception and satisfaction will help in greater acceptance of teledermatology services.

Contrast enhanced ultrasound for characterization of suspected soft tissue vascular anomalies.

BACKGROUND: Evaluation of perfusion characteristics is the key to characterize vascular anomalies. Contrast-enhanced ultrasound (CEUS) is a radiation-free modality to evaluate this in real-time and can be coupled along with Doppler-ultrasound (US). OBJECTIVE: To evaluate the utility of CEUS in characterization of suspected soft-tissue vascular anomalies and compare its diagnostic accuracy with Doppler-US. MATERIALS AND METHODS: This was an ethically-approved cross-sectional study, done from November 2017- November 2019, involving 93 patients (55 M/38F; mean age 23.6 ± 11.9 years) in development cohort and 128 (66 M/62F; mean age 21.4 ± 11.1 years) in validation cohort. Patients suspected to have soft-tissue vascular anomalies on clinical evaluation and US were included. Clinical features, US, Doppler, subjective and quantitative CEUS features (from time-intensity curves) were evaluated. Composite gold standard employing MRI, phlebogram, DSA or biopsy was used to make the final diagnosis. The CEUS features found to be significantly different in the development cohort were prospectively validated in the validation cohort. P-value < 0.05 was considered significant, ROC curves were drawn and threshold values obtained for the various quantitative parameters. A prospective diagnosis was suggested in the validation group along with a degree of diagnostic confidence and accuracy was calculated. RESULTS: The spectrum of lesions included 77 venous malformations, 46 fibro-adipose vascular anomalies, 32 vascular tumors, 20 arteriovenous malformations and 20 lymphatic malformations. All lesions were found to have distinctive temporal and morphological subjective enhancement patterns. Quantitative parameters like rise-time, mean-transit-time, time-to-peak, peak-enhancement showed significant differences between the various groups (P value < 0.05). Addition of CEUS not only increased the diagnostic accuracy of Doppler-US from 76.5% (91/119) to 88.2% (105/119), but also the degree of diagnostic confidence in characterization of soft-tissue vascular anomalies. None of the patients showed any contrast-related adverse effects. CONCLUSION: Contrast-enhanced ultrasound is useful to characterize different types of soft-tissue vascular anomalies and increases the diagnostic accuracy and confidence over Doppler-ultrasound.

Effectiveness and safety of 0.5% timolol solution in the treatment of pyogenic granuloma: A randomized, double-blind and placebo-controlled study.

Introduction Pyogenic granulomas are benign vascular lesions of the skin and mucosa which are often a source of concern because of their recurrent bleeding even with minimal trauma. Current treatment for pyogenic granuloma is ablative; no medical therapy is standardized to date. Timolol, due to its vasoconstrictive effect, vascular growth factor inhibition and apoptosis promotion properties, is a potential therapeutic option. Objectives: To assess the effectiveness and safety of topical timolol in the treatment of pyogenic granulomas. Methods A two-centre, double-blind and placebo-controlled trial (Registration CTRI/2019/04/018581) was conducted. Patients of either sex were recruited with pyogenic granuloma lesions of less than eight weeks duration. Topical treatment with 0.5% timolol or matching glycerin placebo was continued for six weeks. Changes in color, size, bleeding tendency, physicians' and patients' global assessments and adverse events were assessed. Results Forty subjects were randomized between the two groups which were comparable in age, sex, duration of illness and baseline lesion size.Significant improvement was noted with timolol, with color change from first follow-up onwards and lesion size reduction from second follow-up onward. Patients' assessment of bleeding tendency also showed imrovement from the second visit onward. Between-group comparison showed significant difference with respect to percentage reduction in size (timolol 40.9%, placebo 3.4%; P = 0.002). Rescue treatment (electrosurgery) was required in five patients on placebo and in one in the timolol group (P = 0.182). Complete resolution occurred in 2 (10%) patients with timolol and in no patients on placebo (P = 0.231). Limitations: We observed effects of treatment for only six weeks. Conclusion Topical timolol may be a treatment option for early pyogenic granulomas but complete resolution is unlikely in six weeks. Studies of longer duration are required to assess resolution and recurrence rates.

Transethnic analysis of psoriasis susceptibility in South Asians and Europeans enhances fine-mapping in the MHC and genomewide.

Because transethnic analysis may facilitate prioritization of causal genetic variants, we performed a genomewide association study (GWAS) of psoriasis in South Asians (SAS), consisting of 2,590 cases and 1,720 controls. Comparison with our existing European-origin (EUR) GWAS showed that effect sizes of known psoriasis signals were highly correlated in SAS and EUR (Spearman ρ = 0.78; p < 2 × 10-14). Transethnic meta-analysis identified two non-MHC psoriasis loci (1p36.22 and 1q24.2) not previously identified in EUR, which may have regulatory roles. For these two loci, the transethnic GWAS provided higher genetic resolution and reduced the number of potential causal variants compared to using the EUR sample alone. We then explored multiple strategies to develop reference panels for accurately imputing MHC genotypes in both SAS and EUR populations and conducted a fine-mapping of MHC psoriasis associations in SAS and the largest such effort for EUR. HLA-C*06 was the top-ranking MHC locus in both populations but was even more prominent in SAS based on odds ratio, disease liability, model fit and predictive power. Transethnic modeling also substantially boosted the probability that the HLA-C*06 protein variant is causal. Secondary MHC signals included coding variants of HLA-C and HLA-B, but also potential regulatory variants of these two genes as well as HLA-A and several HLA class II genes, with effects on both chromatin accessibility and gene expression. This study highlights the shared genetic basis of psoriasis in SAS and EUR populations and the value of transethnic meta-analysis for discovery and fine-mapping of susceptibility loci.

Stem cell therapy in dermatology.

Stem cells are precursor cells present in many tissues with ability to differentiate into various types of cells. This interesting property of plasticity can have therapeutic implications and there has been substantial research in this field in last few decades. As a result, stem cell therapy is now used as a therapeutic modality in many conditions, and has made its way in dermatology too. Stem cells can be classified on the basis of their source and differentiating capacity. In skin, they are present in the inter-follicular epidermis, hair follicle, dermis and adipose tissue, which help in maintaining normal skin homeostasis and repair and regeneration during injury. In view of their unique properties, they have been employed in treatment of several dermatoses including systemic sclerosis, systemic lupus erythematosus, scleromyxedema, alopecia, Merkel cell carcinoma, pemphigus vulgaris, psoriasis, wound healing, epidermolysis bullosa and even aesthetic medicine, with variable success. The advent of stem cell therapy has undoubtedly brought us closer to curative treatment of disorders previously considered untreatable. Nevertheless, there are multiple lacunae which need to be addressed including ideal patient selection, timing of intervention, appropriate conditioning regimens, post-intervention care and cost effectiveness. Further research in these aspects would help optimize the results of stem cell therapy.