A Delphi consensus on the nomenclature and diagnosis of lichen planus pigmentosus and related entities

Background: Although well known in clinical practice, research in lichen planus pigmentosus and related dermal pigmentary diseases is restricted due to lack of consensus on nomenclature and disease definition. Aims and Objectives: Delphi exercise to define and categorise acquired dermal pigmentary diseases. Methods: Core areas were identified including disease definition, etiopathogenesis, risk factors, clinical features, diagnostic methods, treatment modalities and outcome measures. The Delphi exercise was conducted in three rounds. Results: Sixteen researchers representing 12 different universities across India and Australia agreed to be part of this Delphi exercise. At the end of three rounds, a consensus of >80% was reached on usage of the umbrella term ‘acquired dermal macular hyperpigmentation’. It was agreed that there were minimal differences, if any, among the disorders previously defined as ashy dermatosis, erythema dyschromicum perstans, Riehl’s melanosis and pigmented contact dermatitis. It was also agreed that lichen planus pigmentosus, erythema dyschromicum perstans and ashy dermatosis did not differ significantly apart from the sites of involvement, as historically described in the literature. Exposure to hair colours, sunlight and cosmetics was associated with these disorders in a significant proportion of patients. Participants agreed that both histopathology and dermatoscopy could diagnose dermal pigmentation characteristic of acquired dermal macular hyperpigmentation but could not differentiate the individual entities of ashy dermatosis, erythema dyschromicum perstans, Riehl’s melanosis, lichen planus pigmentosus and pigmented contact dermatitis. Limitations: A wider consensus involving representatives from East Asian, European and Latin American countries is required. Conclusion: Acquired dermal macular hyperpigmentation could be an appropriate conglomerate terminology for acquired dermatoses characterised by idiopathic or multifactorial non-inflammatory macular dermal hyperpigmentation

Randomized controlled study to evaluate the effectiveness of dexamethasone oral minipulse therapy versus oral minocycline in patients with active vitiligo vulgaris.

Background: Oral minocycline has been recently shown to halt disease progression in active vitiligo. Aims: The present study was planned to compare the efficacy and tolerability of oral minocycline with oral mini pulse (OMP) corticosteroids in active vitiligo. Methods: A total of 50 patients with actively spreading vitiligo were randomized to receive either minocycline 100 mg/day (Group I - 25 patients) or OMP 2.5 mg dexamethasone on 2 consecutive days in a week (Group II - 25 patients) for 6 months. These were followed-up at every 2 weeks interval. Mean vitiligo disease activity score (VIDA) and mean Vitiligo Area Scoring Index (VASI) were assessed in all patients in addition to the photographic comparison before and after treatment. Results: Both groups showed a significant decrease in VIDA from 4.0 to 1.64 ± 0.86 (P < 0.001) in Group I and from 4.0 to 1.68 ± 0.69 (P < 0.001) in Group II. However, the difference between the mean VIDA scores in the two groups was not statistically significant (P = 0.60) at the end of treatment period. The mean VASI declined from 1.71 ± 1.45 to 1.52 ± 1.43 Group I (P = 0.06) and from 1.39 ± 1.31 to 1.17 ± 1.34 in Group II (P = 0.05). The difference between VASI in Group I and II was not significant at the end of 24 weeks of treatment (P = 0.11). Conclusion: Both dexamethasone OMP and oral minocycline are effective drugs for managing the arrest of disease activity in vitiligo.

Assessment of the therapeutic benefit of dexamethasone cyclophosphamide pulse versus only oral cyclophosphamide in phase II of the dexamethasone cyclophosphamide pulse therapy: A preliminary prospective randomized controlled study.

Background: Dexamethasone cyclophosphamide pulse (DCP) therapy is an established mode of treatment for pemphigus in India. Aims: To assess the therapeutic benefit of additional DCPs (phase II, consolidation phase) versus immediate oral cyclophosphamide, usually used in phase III (maintenance phase), after initial DCP therapy (phase I) and to assess which laboratory test (DIF or ELISA) will reflect the clinical relapse best. Methods: Nineteen newly recruited patients of pemphigus vulgaris (PV) received monthly DCPs in phase I and were then randomized into two groups. Group A (10 patients) received monthly DCPs for nine months and Group B (nine patients) received only oral cyclophosphamide for nine months. Direct immunofluorescence (DIF) and enzyme-linked immunosorbent assay (ELISA) were tested before starting DCP regimen, and at 0,3,6,9 months after randomization. Results: Clinical relapse by the end of follow-up period occurred in only one patient in each group. In these cases, DIF became (again) positive before the relapse. No statistically significant difference between the two groups was found at three, six and nine months by ELISA indices and DIF grading. Conclusion: Although the DCP regimen is the standard therapy for pemphigus in India, we found no difference in the clinical outcome between patients receiving nine DCPs in phase II and patients shifted directly from phase I to III. Periodic testing using DIF and Dsg ELISA were found to be useful to monitor disease activity and predict a relapse. Further large scale studies are required to assess if patients can be shifted directly from phase I to III and maintained only on oral cyclophosphamide.

Development of melanocye-keratinocyte co-culture model for controls and vitiligo to assess regulators of pigmentation and melanocytes.

Background: There is a need to develop an in vitro skin models which can be used as alternative system for research and testing pharmacological products in place of laboratory animals. Therefore to study the biology and pathophysiology of pigmentation and vitiligo, reliable in vitro skin pigmentation models are required. Aim: In this study, we used primary cultured melanocytes and keratinocytes to prepare the skin co-culture model in control and vitiligo patients. Methods: The skin grafts were taken from control and patients of vitiligo. In vitro co-culture was prepared after culturing primary melanocytes and keratinocytes. Co- cultures were treated with melanogenic stimulators and inhibitors and after that tyrosinase assay, MTT assay and melanin content assay were performed. Results: Melanocytes and keratinocytes were successfully cultured from control and vitiligo patients and after that co-culture models were prepared. After treatment of co-culture model with melanogenic stimulator we found that tyrosinase activity, cell proliferation and melanin content increased whereas after treatment with melanogenic inhibitor, tyrosinase activity, cell proliferation and melanin content decreased. We also found some differences in the control co-culture model and vitiligo co-culture model. Conclusion: We successfully constructed in vitro co-culture pigmentation model for control and vitiligo patients using primary cultured melanocytes and keratinocytes. The use of primary melanocytes and keratinocytes is more appropriate over the use of transformed cells. The only limitation of these models is that these can be used for screening small numbers of compounds.

Melanocytorrhagy and apoptosis in vitiligo: Connecting jigsaw pieces.

Vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and follicular reservoir. The mechanism of melanocyte disappearance has never been clearly understood. This review discussed the data supporting the theory of melanocytorrhagy and apoptosis as one of the primary defects underlying melanocyte loss. Theory of melanocytorrhagy proposes that non-segmental vitiligo is a primary melanocytorrhagic disorder with altered melanocyte responses to friction and possibly other types of stress, inducing their detachment and subsequent transepidermal loss. Melanocytes detachment induces apoptosis whereas adherence to basement membrane suppresses apoptosis. The study of apoptosis, mechanisms of its induction, and the ways to block apoptosis is one possible way to find both the causes of depigmentation and medications to prevent its progression.

Standard guidelines of care for vitiligo surgery.

Vitiligo surgery is an effective method of treatment for selected, resistant vitiligo patches in patients with vitiligo. PHYSICIAN'S QUALIFICATIONS: The physician performing vitiligo surgery should have completed postgraduate training in dermatology which included training in vitiligo surgery. If the center for postgraduation does not provide education and training in cutaneous surgery, the training may be obtained at the surgical table (hands-on) under the supervision of an appropriately trained and experienced dermatosurgeon at a center that routinely performs the procedure. Training may also be obtained in dedicated workshops. In addition to the surgical techniques, training should include local anesthesia and emergency resuscitation and care. FACILITY: Vitiligo surgery can be performed safely in an outpatient day care dermatosurgical facility. The day care theater should be equipped with facilities for monitoring and handling emergencies. A plan for handling emergencies should be in place, with which all nursing staff should be familiar. Vitiligo grafting for extensive areas may need general anesthesia and full operation theater facility in a hospital setting and the presence of an anesthetist is recommended in such cases. INDICATIONS FOR VITILIGO SURGERY: Surgery is indicated for stable vitiligo that does not respond to medical treatment. While there is no consensus on definitive parameters for stability, the Task Force suggests the absence of progression of disease for the past one year as a definition of stability. Test grafting may be performed in doubtful cases to detect stability. PREOPERATIVE COUNSELING AND INFORMED CONSENT: A detailed consent form elaborating the procedure and possible complications should be signed by the patient. The patient should be informed of the nature of the disease and that the determination of stability is only a vague guide. The consent form should specifically state the limitations of the procedure, about the possible future progression of disease and whether more procedures will be needed for proper results. The patient should be provided with adequate opportunity to seek information through brochures and one-to-one discussions. The need for concomitant medical therapy should be emphasized and the patient should understand that proper results take time (a few months to a year). Preoperative laboratory studies include hemogram including platelet counts, bleeding and clotting time (or prothrombin and activated partial thromboplastin time), and blood chemistry profile. Screening for antibodies for hepatitis B surface antigen and HIV is recommended depending on individual requirements. ANESTHESIA: Lignocaine (2%) with or without adrenaline is generally used for anesthesia; infiltration and nerve block anesthesia are adequate in most cases. General anesthesia may be needed in patients with extensive lesions. POSTOPERATIVE CARE: Proper postoperative immobilization and care are very important to obtain satisfactory results.