Safety and efficacy of autologous noncultured dermal cell suspension transplantation in the treatment of localized facial volume loss: A pilot study

Background: Available options for correction of facial volume loss, such as synthetic fillers, autologous fat and cultured fibroblasts, have limitations viz. temporary effect and high cost. Aim: To assess the use of a novel technique, autologous non-cultured dermal cell suspension transplantation, for correction of localized facial volume loss due to inflammatory pathologies. Methods: It was a pilot study conducted in the Dermatology Outpatient Department, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Autologous non-cultured dermal cell suspension was transplanted in a total of 10 patients, out of which 5 had predominantly dermal loss and the rest had predominantly lipoatrophy. The donor tissue from the gluteal region was digested into a single cell suspension using collagenase-1 and injected into the recipient area. The outcome was assessed subjectively by patients and investigators and objectively using ultrasonography. Cell count, viability testing and measurement of mesenchymal stem cells were also done. Results: On assessment of patients, the median improvement in the predominantly dermal atrophy group at 3 and 6 months was 70% (range: 10–90%) and 80% (range: 0–90%), respectively, and in the predominantly lipoatrophy group, 0% (range: 0–40) and 0% (range: 0–50), respectively. Mean thickness of dermis + subcutis at the baseline was 1.835 mm (range: 0.89–6.04 mm), which increased to 2.912 mm (range: 0.88–7.07 mm, P = 0.03) at 6 months. Limitations: Our pilot study has some limitations such as small sample size and heterogeneity of the recruited patients. Conclusions: Autologous non-cultured dermal cell suspension transplantation appears to be safe and effective in localized facial dermal defects because of inflammatory pathologies, but not effective in deeper defects.

Prevalence of metabolic syndrome and cardiovascular changes in patients with chronic plaque psoriasis and their correlation with disease severity: A hospital-based cross-sectional study.

Background: Previous epidemiological studies suggest an association between psoriasis and metabolic syndrome and risk of subclinical atherosclerosis. However, there is a paucity of data in the Indian population on these associations. Objectives: To evaluate the prevalence of metabolic syndrome and subclinical atherosclerosis in patients with chronic plaque psoriasis compared to healthy controls and to correlate the prevalence of metabolic syndrome with severity of psoriasis. Methods: A hospital-based cross-sectional study was performed on 140 patients with chronic plaque psoriasis and 140 controls. Psoriasis was categorized as mild, moderate and severe based on psoriasis area and severity index (<10, 10–14 and ≥15, respectively) and as disease of short (<1 year), intermediate (1–3 years) and long duration (>3 years). In all patients and controls, body mass index was calculated, blood pressure and waist circumference were measured and fasting blood sugar and lipid profi le were estimated. Metabolic syndrome was diagnosed by the presence of 3 or more of the modifi ed National Cholesterol Education Program’s Adult Treatment Panel III criteria. A subset of 30 psoriatic patients and 30 healthy controls were selected by the systematic sampling method for cardiac evaluation including electrocardiography, echocardiography and carotid intima-media thickness measurement. Results: The prevalence of metabolic syndrome was signifi cantly more in psoriatic patients than in controls (39.3% vs. 17.1%, odds ratio = 3.13). Psoriatic patients also had a signifi cantly higher prevalence of hypertension, abdominal obesity and diabetes. There was a signifi cant trend to increase in prevalence of metabolic syndrome, hypertension and type 2 diabetes with increased severity and longer duration of the psoriasis. Patients with psoriasis had signifi cantly higher carotid intima-media thickness (mean 0.61 mm ± 0.01 mm vs. 0.37 mm ± 0.01 mm) than controls. Limitation: This was a hospital-based cross-sectional study with a relatively small sample size. A prospective study with a larger sample would have validated the results further. Conclusion: There is a signifi cantly higher prevalence of metabolic syndrome in psoriasis patients as compared to controls; the prevalence of metabolic syndrome and its components increases with severity and duration of psoriasis. There is a higher prevalence of subclinical atherosclerosis in patients with psoriasis thus increasing the risk of cardiovascular disease. We suggest that patients with moderate to severe psoriasis be screened routinely for metabolic syndrome and cardiovascular disease and encouraged to correct modifi able cardiovascular risk factors.

A study of the clinico-histopathological features of erythematous tender nodules predominantly involving the extremities.

Background: Erythematous tender nodules predominantly involving extremities are frequently encountered in dermatology and rheumatology practice. They are diagnosed based on distinct clinical and histopathological features. However, in clinical situations, considerable overlap is observed that poses a diagnostic challenge. We undertook a study on clinico-histological patterns of inflammatory nodules over extremities. Methods: After detailed history and examination, a preliminary clinical diagnosis was made in 43 cases, followed by skin biopsy from representative nodules. Histological diagnosis made was correlated with clinical features. Results: Of 43 cases, a single clinical diagnosis was made in 25 (58.5%) cases while in the remaining cases more than one diagnosis was considered. On correlating with the histopathological diagnosis, concordance was observed in 51% cases while the remaining showed either histological discordance with clinical diagnosis (14% cases) or were kept in the undecided category (35% cases). Conclusion: Considerable clinico-histological overlap was observed in inflammatory nodules over extremities. Histopathology alone was not helpful in differentiating one entity from another at all times since variable histo-pathological patterns were seen.

A randomized placebo-controlled double-blind pilot study of methotrexate in the treatment of H1 antihistamine-resistant chronic spontaneous urticaria.

Background: Chronic urticaria not responsive to antihistamines is a diffi cult disease to manage. Methotrexate has been used in diffi cult chronic urticarias with some benefi t. Objective: To evaluate the effi cacy of methotrexate in the treatment of chronic spontaneous urticaria poorly responsive to H1 antihistaminics. Methods: In a randomized double-blind trial at the Department of Dermatology and Venereology of a tertiary care centre, 29 patients with chronic spontaneous urticaria not responding well to H1 antihistaminics were recruited. Patients were randomly allocated to receive either a weekly dose of oral methotrexate 15 mg or placebo (calcium carbonate) for a total duration of 12 weeks, after which treatment was stopped and patients were followed up for relapse of urticaria. Each group also received levocetrizine 5 mg once daily for symptom control. Primary outcome measured was a reduction by >2/3rd of baseline urticaria scores after 12 week therapy. Secondary outcome was a reduction in antihistamine requirement after stopping therapy. Results: Fourteen patients were randomized to the methotrexate group and fi fteen patients to the placebo group. Out of 17 patients who completed therapy, the primary outcome was achieved by 3.5 ± 1.9 (out of 10) patients in the methotrexate group and by 3.67 ± 1.03 (out of 7) patients in the placebo group (P > 0.05). Ten patients followed up, after stopping therapy, for a mean period of 3.5 ± 2.4 months; 3 remained in remission and 7 had relapsed. One patient had uncontrollable nausea and vomiting after taking methotrexate and was withdrawn from the study. The placebo group did not experience any side effects. Conclusions: Methotrexate 15 mg weekly for 3 months did not provide any additional benefi t over H1 antihistamines in this study but an adequately powered study with longer follow up is required to assess its utility.

The psychosocial impact of vitiligo in Indian patients.

Background: Vitiligo has a special significance in Indian patients both because depigmentation is obvious on darker skin and the enormous stigma associated with the disease in the culture. Aims: This study was carried out to determine the beliefs about causation, aspects of the disease that cause concern, medical, and psychosocial needs of the patients, expectation from treatment and from the treating physician, and effects of disease on the patient's life. Methods: Semi-structured interviews were conducted in 50 patients with vitiligo. Purposive sampling was used to select subjects for the study. Each interview was recorded on an audio-cassette and transcripts were analyzed to identify significant issues and concerns. Results: Patients had a range of concerns regarding their disease such as physical appearance, progression of white patches onto exposed skin and the whole body, ostracism, social restriction, dietary restrictions, difficulty in getting jobs, and they considered it to be a significant barrier to getting married. The condition was perceived to be a serious illness. Stigma and suicidal ideation was reported. While there were several misconceptions about the cause of vitiligo, most patients did not think their disease was contagious, heritable or related to leprosy. Multiple medical consultations were frequent. Complete repigmentation was strongly desired, but a lesser degree of repigmentation was acceptable if progression of disease could be arrested. The problems were perceived to be more severe in women. The disease imposed a significant financial burden. Conclusion: Addressing psychosocial factors is an important aspect of the management of vitiligo, particularly in patients from communities where the disease is greatly stigmatizing.

Photosensitive spongiotic/lichenoid eruption of micropapules and plaques: A morphologically distinct entity.

Background: A distinct morphological pattern of photodermatosis has been observed with shiny skin colored to hypopigmented tiny papules, discrete or coalescing to form plaques. Aims: To study the clinico-pathological features of patients presenting with these lesions. Methods: A total of 72 patients were recruited. Clinical examination and skin biopsy was carried out to evaluate the morphological patterns and the histopathological features. Results: In all patients, tiny discrete to coalescent papules were observed on sun-exposed sites but usually sparing the face. The condition occurred more commonly in women. Three specific histopathological patterns were observed : 0 spongiotic (43.7%), lichenoid (22.5%), psoriasiform (18.7%) and also perivascular pattern in 5%. Conclusion: Photosensitive lichenoid eruption is a morphologically distinct photodermatoses that is commonly seen in Indian patients with pathological features showing mostly spongiotic changes and in some cases lichenoid changes.

Vitiligo impact scale: An instrument to assess the psychosocial burden of vitiligo.

Background : Vitiligo is a disease that significantly impairs quality of life. Previous studies have shown that vitiligo has an impact that may not correlate with the size and extent of depigmentation, indicating a need for an independent measure of the psychosocial burden. Aims : To develop a rating scale to assess the psychosocial impact of vitiligo. Methods : The study was undertaken in three broad phases: item generation, pre- and pilot testing, and test administration. Items were generated largely from a qualitative study using semi-structured interviews of patients. Face and content validity were assessed through pre- and pilot testing in 80 patients and the final version was administered to 100 patients who also received the Dermatology Life Quality Index (DLQI) and the Skindex-16. Each patient also underwent a physician global assessment (PGA) of the impact of vitiligo. Test-retest reliability was assessed in 20 patients. Results: Of 72 items initially generated for the scale, 27 were retained in the final version. Subjects were able to comprehend the items and took about 5-7 min to complete the instrument. The scale was internally consistent (Cronbach's α = 0.85). Scores on the scale correlated moderately well with the DLQI and the Skindex (Spearman rank correlation: 0.51 and 0.65, respectively). The scale was able to discriminate between patients having mild and those having moderate and severe impact as assessed by PGA. The test-retest reliability coefficient (Spearman rank correlation) was 0.80. Conclusion: The Vitiligo Impact Scale appears to be a valid measure of the psychosocial impact of vitiligo and this instrument may be useful both in the clinic and in clinical trials.

mRNA and DNA PCR tests in cutaneous tuberculosis.

Background: The microbiologic diagnosis of cutaneous tuberculosis is difficult because most lesions harbor only a small number of mycobacteria that cannot usually be detected by staining for the organism or by culture. Nucleic acid amplification tests based on the polymerase chain reaction (PCR) are potentially useful in this situation. Aims: To evaluate the utility of mRNA PCR and DNA PCR in the diagnosis of cutaneous tuberculosis. Methods: Biopsies from 28 cases of cutaneous tuberculosis and 19 controls with other diseases were subjected to microbiologic tests including direct smears for mycobacteria, culture and both mRNA PCR and DNA PCR. The laboratory was blinded to the clinical diagnosis. Results: None of the patients or controls showed a positive reaction on mRNA PCR test. Seven of 28 cases and 5 out of 19 controls showed a positive result on DNA PCR test yielding a sensitivity of 25% and a specificity of 73.7%. Conclusion: The results of PCR tests in cutaneous tuberculosis should be interpreted in the light of clinical and histopathological findings.

Oral drug provocation test to generate a list of safe drugs: Experience with 100 patients.

Background: Following a drug eruption, patients and their doctors need to know which drugs can be safely administered for subsequent illnesses. Currently available laboratory tests are unable to answer this question in a clinically meaningful manner. Aims: To describe our use of oral provocation tests to provide a list of safe drugs to patients. Methods: We studied the records of 100 patients who underwent oral provocation testing in our department between 2003 and 2009. All patients were admitted to hospital and drugs were administered under supervision, one drug per day. A dermatologist evaluated all symptoms and signs that developed following drug intake. Results: Sixty nine women and 31 men underwent provocation testing. There were 96 reactions in 61 patients, of which 44 reactions in 34 patients were judged to be true reactions. All reactions could be controlled, with treatment or spontaneously. A list of safe drugs was provided to the patient along with written instructions to avoid any drug(s) that had produced a reaction. Conclusions: Oral provocation tests are safe and effective in providing patients with a list of drugs they can take safely. These tests should preferably be undertaken after admitting the patient to hospital.

Parthenium dermatitis in India: Past, present and future.

Parthenium dermatitis is an immuno-inflammatory disease caused by Parthenium hysterophorus and is the commonest cause of plant dermatitis in India. It is caused by airborne dry and friable plant particles including trichomes, and the most important allergens responsible for allergic contact dermatitis are sesquiterpene lactones. The combined type IV and type I hypersensitivity to parthenium has been recently postulated. In sensitized individuals, it can cause a spectrum of clinical patterns, such as classical airborne pattern, chronic actinic dermatitis-like presentation, mixed pattern dermatitis, exfoliative dermatitis, widespread dermatitis, and other rare patterns. There is definite trend towards change from airborne pattern to chronic actinic pattern in natural history of parthenium dermatitis. Contact sensitivity to parthenium is everlasting, and hence the disease runs a chronic course with exacerbation during summers. Patch testing with acetone or aqueous plant extract is the simplest way of confirming parthenium contact allergy. Management includes avoiding contact with allergen, managing dermatitis with topical corticosteroids/tacrolimus, and other immunosupressives like azathioprine. In future, we expect parthenium dermatitis to become less prevalent due to rapid urbanization and possible development of new biological methods to eradicate the parthenium. Genetic factors associated with susceptibility to parthenium dermatitis need to be studied.

Segmental vitiligo: A randomized controlled trial to evaluate efficacy and safety of 0.1% tacrolimus ointment vs 0.05% fluticasone propionate cream.

Background: Segmental vitiligo is a small subset of vitiligo which responds very well to surgical therapy, but the role of medical treatment is not very well defined. Aim: To compare the efficacy and safety of 0.1% tacrolimus ointment versus 0.05% fluticasone propionate cream in patients of segmental vitiligo. Methods: A randomized control trial was conducted in a tertiary care hospital on 60 consecutive patients with segmental vitiligo. Patients with segmental vitiligo exclusively or along with focal vitiligo, untreated or had not taken any topical treatment in previous 1 month or systemic treatment in previous 2 months, from May 2005 to January 2007, were block randomized into two groups. Children <5 years, pregnant and lactating women, and patients with known hypersensitivity to either drug and with associated multiple lesions of vitiligo were excluded. Group A (n = 29) patients were treated with tacrolimus 0.1% ointment twice daily and group B (n = 31) patients were treated with 0.05% of fluticasone cream once daily for 6 months. Response and side effects were recorded clinically and by photographic comparison. Results: Nineteen patients treated with tacrolimus and 21 patients treated with fluticasone completed the treatment with median repigmentation of 15% and 5%, respectively, at 6 months (P = 0.38). Transient side effects limited to the application site were observed. Conclusions: Both tacrolimus and fluticasone propionate produce variable but overall unsatisfactory repigmentation in segmental vitiligo.

An aetiological & clinicopathological study on cutaneous vasculitis.

Background & objectives: Cutaneous vasculitis has protean clinical manifestations. It may be idiopathic or associated with a spectrum of conditions such as infections, drugs, etc. Skin is involved in both small vessel vasculitis (SVV) and medium vessel vasculitis (MVV). Overlapping features are seen between SVV and MVV. The histopathological features may not always relate with the clinical lesions. The aim of the present study was to evaluate the aetiological factors and clinicopathological association in patients with cutaneous vasculitis. Methods: In this cross-sectional study, detailed history and clinical examination were done on patients with biopsy proven cutaneous vasculitis. Two skin biopsies were taken from each patient for routine histopathology and direct immunofluorescence. Results: Of the 61 patients studied, hypersensitivity vasculitis (HSV) [23 (37.7%)] and Henoch Schonlein purpura (HSP) [16 (26.2%)] were the two most common forms. Systemic involvement was seen in 32 (52.45%) patients. Drugs were implicated in 12 (19.7%) cases, infections in 7 (11.4%) and connective tissue disorders in 4 (6.5%) cases. Histologically SVV was the most common pattern, seen in all the clinically diagnosed patients with SVV (47), and in 12 of the 14 clinically diagnosed patients with MVV. Direct immunofluorescence showed positivity for at least one immunoreactant in 62 per cent of the patients and the most common deposit was C3 followed by IgG, IgA and IgM. Interpretation & conclusions: Majority of our patients with cutaneous vasculitis were idiopathic. Histologically, SVV was seen in most of our patients. No association was seen between history of drug intake and tissue eosinophilia and also between histologically severe vasculitis and clinical severity. The presence of immunoreactant IgA was not specific for HSP.

Organic matrix based slow release fertilizer enhances plant growth, nitrate assimilation and seed yield of Indian mustard (Brassica juncea L.).

Field experiments were conducted to study the effect of organic matrix based slow release fertilizers (SRFs) on plant growth, nitrate assimilation and seed yield of Brassica juncea L. cv. pusa bold. The agro-waste materials like cow dung, clay soil, neem leaves and rice bran were mixed together in 2:2:1:1 ratio and used as organic matrix for the immobilization of chemical fertilizer nutrients with commercial grade saresh (Acacia gum, 15% solution) as binder. Different fertilizer treatments were organic matrix based slow release fertilizers, SRF-I (542.0 kg ha-1); SRF-II (736.5 kg ha-1) and chemical fertilizer combinations, boron (3 kg ha-1)+sulphur (15 kg ha-1)+nitrogen (80 kg ha-1) and boron (3 kg ha-1) + sulphur (15 kg ha-1)+nitrogen (80 kg ha-1)+phosphorus (15 kg ha-1)+potassium (100 kg ha-1). Organic matrix based SRF-II released ammonium up to 50-d in wet soil under laboratory conditions which showed maximum retention of the nutrients. A very significant increase in plant growth, nitrate assimilation and seed yield was recorded in organic matrix based SRF-II applied plants. The maximum percent increase in biomass production was observed with organic matrix based SRF-II (increase of 65.8% in root fresh weight, 38.0% in root dry weight, 45.9% in leaf fresh weight plant-1 and 27.5 % in leaf dry weight plant-1 in 60-d old plants). It also increased the acquisition and assimilation of nitrate from the plant’s rhizosphere which was evident by 45.6% increase in nitrate, 27.5% in nitrite and 11.7% in nitrate reductase activity (NRA) in leaves of 45-d old plants over control. The organic matrix based SRF-II significantly increased the seed yield by 28% in Indian mustard. Cost analysis revealed that this formulation is cost effective as it is based on agro waste materials.

Pediatric contact dermatitis.

Allergic contact dermatitis (ACD) in children, until recently, was considered rare. ACD was considered as a disorder of the adult population and children were thought to be spared due to a lack of exposure to potential allergens and an immature immune system. Prevalence of ACD to even the most common allergens in children, like poison ivy and parthenium, is relatively rare as compared to adults. However, there is now growing evidence of contact sensitization of the pediatric population, and it begins right from early childhood, including 1-week-old neonates. Vaccinations, piercing, topical medicaments and cosmetics in younger patients are potential exposures for sensitization. Nickel is the most common sensitizer in almost all studies pertaining to pediatric contact dermatitis. Other common allergens reported are cobalt, fragrance mix, rubber, lanolin, thiomersol, neomycin, gold, mercapto mix, balsum of Peru and colophony. Different factors like age, sex, atopy, social and cultural practices, habit of parents and caregivers and geographic changes affect the patterns of ACD and their variable clinical presentation. Patch testing should be considered not only in children with lesions of a morphology suggestive of ACD, but in any child with dermatitis that is difficult to control.