Changes in Cytokine Profile with Immunotherapy in Viral Warts using Purified Protein Derivative, Mumps Measles Rubella Vaccine, and Mycobacterium w Vaccine.

BACKGROUND: Immunotherapy for wart employs ability of immune system to recognize certain viral, bacterial, and fungal antigens in previously sensitized individual inducing Type IV delayed-type hypersensitivity reaction (up-regulated Th1 cytokines IL-1, TNF-α, IFN-γ; down-regulated Th2 cytokines IL-10), not only to injected antigen but also against wart virus. AIMS: To evaluate and compare the pattern of production of Th1 cytokines (IL-1, TNF-α, IFN-γ) and Th2 cytokines (IL-10) in patients receiving immunotherapy with purified-protein-derivative (PPD), Mycobacterium w (Mw), or mumps-measles-rubella (MMR) vaccine. METHODS: The cohort study conducted on patients receiving immunotherapy with PPD, Mw, or MMR which was injected intradermally at baseline, repeated every 2 weeks for 6 doses?. Five-millilit?e?r blood was collected for evaluation of cytokines at baseline and 12 weeks of treatment. Blood was centrifuged to separate serum, stored at -80°C. Cytokines were measured by ELISA using a standard kit. RESULTS: Nine participants in PPD group, 11 in Mw group, and 12 in MMR group completed the study. IL-1 was raised from baseline in all study arms and was significant in PPD group (P = 0.008). There was a predicted increase in IFN-γ in Mw and MMR groups but not in the PPD group. In the PPD group, IFN-γ was found to be down regulated. IL-10, a Th 2 cytokine was down regulated in all the groups at the study end from baseline, significantly so in the PPD group (P = 0.027) and MMR group (P = 0.001). TNF-α, being a Th1 cytokine was down regulated in all groups instead of an increase. In PPD group, IL-10 was significantly low at study end in patients who had complete resolution of warts. LIMITATIONS: Longer follow-up could not be done due to logistic issues. CONCLUSION: IL-1, TNF-α upregulation and IL-10 downregulation confirm that cytokine milieu plays an important role in wart immunotherapy. TNF-α has no contributory role. IL-10 can be used as a biomarker of complete response in PPD therapy.

Exploring the safety and effectiveness of subcutaneous autologous serum therapy versus conventional intramuscular autologous serum therapy in chronic urticaria: An observer-blind, randomized, controlled study.

BACKGROUND: Autologous serum therapy aims to supplement the existing pharmacotherapy in chronic urticaria by decreasing the antihistamine pill-burden and maintaining symptom-free interval. Subcutaneous autologous serum therapy further modifies the amount of serum (2 mL to 1 mL) and gauge of a needle (24G to 31G) to improve compliance and facilitate ease of application. OBJECTIVES: To assess clinical effectiveness and safety of subcutaneous autologous serum therapy versus conventional intramuscular autologous serum therapy and to compare the quality of life in the two treatment arms. METHODS: Institution-based, assessor-blind, prospective, randomized, parallel-group, active-controlled trial with 32 patients in each treatment arm and analyzed on a modified intention to treat principle. After baseline autologous serum skin test, autologous serum was injected as per randomization every week for 9 consecutive weeks. RESULTS: Among the study population, conventional intramuscular autologous serum therapy and subcutaneous autologous serum therapy had a comparable duration of disease (P = 0.164, Mann-Whitney U test), autoreactive status (P = 0.796), urticaria total severity score (P = 0.637) and urticaria activity score summed up over 7 days (P = 0.982). Both urticaria activity score summed up over 7 days and total severity score along with antihistamine pill-burden reduced significantly (P < 0.001, Friedman's analysis of variance) in both subcutaneous autologous serum therapy and conventional intramuscular autologous serum therapy from first follow-up onwards (P < 0.05, Post hoc Dunn's test). Significant improvement was noted in patient's as well as physician's global assessment of disease activity improvement scale (P < 0.001, Friedman's analysis of variance). Intergroup analysis showed that there was no significant difference in urticaria activity score summed up over 7 days either at baseline (P = 0.982, Mann-Whitney U test) or at study end (P = 0.398, Mann-Whitney U test). Similar comparable results were found in the total severity score at the end of the study (P = 0.345, Mann-Whitney U test). Dermatology life quality index showed marked improvement with both types of treatment (P < 0.0001, Wilcoxon test), and the intergroup comparison showed comparable dermatology life quality index values (P = 0.994, Mann-Whitney U test). The pain score at the injection site was more with conventional intramuscular autologous serum therapy than subcutaneous autologous serum therapy (P = 0.0115, Mann-Whitney test). Younger age and lower baseline total severity scores were associated with a better therapeutic response. Baseline urticaria activity score added up over a period of 7 days and total severity scores and the diameter of lesions showed a positive correlation with response pattern. LIMITATION: Basophil histamine release assay not done. Logistics could not support follow-up beyond the end of treatment. CONCLUSION: Subcutaneous autologous serum therapy is not inferior to conventional intramuscular autologous serum therapy with the additional advantage of less pain and operational feasibility.

A Randomized, Double-blind Study of Amorolfine 5% Nail Lacquer with Oral Fluconazole Compared with Oral Fluconazole Alone in the Treatment of Fingernail Onychomycosis.

BACKGROUND: It is a challenge to treat onychomycosis due to frequent treatment failures and relapses. Systemic and topical therapies need to be combined to improve cure rates. Antifungal susceptibility might play a role in the treatment resistance of onychomycosis. AIMS: To compare the safety and effectiveness of amorolfine 5% nail lacquer + oral fluconazole versus only oral fluconazole in the treatment of fingernail onychomycosis. METHODOLOGY: In this double-blind trial (CTRI/2015/02/005369), patients were randomized (1:1) into amorolfine 5% nail lacquer + fluconazole and dummy lacquer + fluconazole. Treatment was given for 3 months with monthly follow-ups. Antifungal sensitivity was carried out for Candida. Effectiveness was assessed by reduction in the number and percentage area of nails involved and mycological cure. At the end of 3-month treatment period, the association between drug sensitivity and treatment response was explored for the Candida infections. RESULTS: Among 30 study participants, the combination group showed significantly lower number of nail involvement (P = 0.004) and percentage nail involvement (P = 0.005) than only fluconazole group. Pretreatment fungal culture showed a comparable number of dermatophytes, Candida, Aspergillus in both the groups. Sensitivity testing was done for the isolated Candida species. Antifungal sensitivity for Candida (n = 11) was tested, and 8 (72.7%) of the organisms were sensitive to fluconazole (minimum inhibitory concentration [MIC] 1.25 ± 1.19 µg/ml), 100% were sensitive to itraconazole (MIC 0.0726 ± 0.021 µg/ml), and 3 (27.3%) were susceptible-dose dependent (S-DD) to fluconazole (MIC 16 µg/ml). Fluconazole only group patients with Candida who showed resistance to fluconazole did not respond to therapy; however, patients in the combination group showed moderate improvement (reduction in area involvement = 55.56 ± 35.36%). CONCLUSION: The combination of amorolfine/fluconazole achieved a higher cure rate not only for sensitive fungus but also for those which were S-DD to fluconazole.

A double-blind, randomized controlled trial to compare the effectiveness and safety of purified protein derivative of tuberculin antigen with Mycobacterium w vaccine in the treatment of multiple viral warts.

BACKGROUND: Present day therapeutic modalities for viral warts are mostly ablative in nature, limited by high recurrence rates and are unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: This study aimed at comparing efficacy and safety of and quality of life changes with intradermal purified protein derivative (PPD) of tuberculin antigen and Mycobacterium w (Mw) vaccine in immunotherapy of warts. METHODS: Patients with multiple (≥5) warts were randomized (1:1) into two groups (PPDand, Mw vaccine groups). Fortnightly, 0.1 ml of either medicine was injected intradermally over the deltoidregion till complete resolution or a maximum of six doses. Patients were followed-up for another 3 months for recurrence. RESULTS: Sixty-four participants received either PPD or Mw vaccine. The number of warts were comparable at baseline (P = 0.089, Mann-Whitney test), and reduced significantly with treatment in both groups (P < 0.001, Friedman's ANOVA), as seen from the fourth follow-up onwards with Mw and fifth follow-up onwards with PPD (P < 0.05, Post hoc Dunn's test). Intergroup comparison showed significantly more (P < 0.05, Mann-Whitney test) reduction with Mw than PPD at the sixth and seventh follow-up. The size of warts also reduced significantly (P < 0.001) in both groups from the third follow-up onwards. Complete remission was more (P = 0.539, Fischer's exact test) in the Mw group (68.8%) than the PPD group (50%); and was significantly higher (P = 0.049, Mann-Whitney test) in patients having shorter duration of warts. Adverse events were significantly more (P < 0.001) with Mw including ulceration (50%), discharge (15.6%), pain-swelling-induration and scar at the injection site (97% each), whereas some of those receiving PPD noted erythema and scaling at the injection site (18.8%), and post-inflammatory hyperpigmentation (12.5%). No recurrence was seen till the end of the study. LIMITATION: Unicentric trial. CONCLUSION: Intradermal injection of Mw vaccine was more effective but had a higher incidence of adverse effects compared to PPD of tuberculin antigen in patients with warts.

A randomized, double-blind trial of amorolfine 0.25% cream and sertaconazole 2% cream in limited dermatophytosis.

BACKGROUND: Dermatophytosis is becoming increasingly unresponsive to conventional antifungals. Newer topical antifungals may be more effective in these patients. AIMS: To evaluate and compare the efficacy and safety of amorolfine 0.25% cream and sertaconazole 2% cream in limited tinea cruris/corporis. METHODS: A single-center, randomized (1:1), double-blind, parallel group, active-controlled trial (CTRI/2014/12/005246) was performed. Sixty-six untreated adults with acutely symptomatic tinea cruris/corporis were included in the study. All patients had limited cutaneous involvement and were KOH mount positive. Group A received amorolfine 0.25% cream, and group B received sertaconazole 2% cream twice daily application to the lesions for 4 weeks. After the baseline visit, four follow-up visits were carried out. The outcome measures for effectiveness were clinical and mycological cure. Safety parameters studied were treatment-emergent adverse events and changes in routine laboratory parameters. RESULTS: Both sertaconazole and amorolfine significantly reduced symptoms (P < 0.001) in both groups. However, improvement in symptoms (pruritus, burning sensation, erythema, scaling and crusting) was significantly greater in the sertaconazole group at every follow-up visit. Sertaconazole cream was also more effective than amorolfine cream in reducing the number of lesions (P = 0.002 at 12 weeks) and improving the Dermatology Life Quality Index (P < 0.001) at all the follow-up visits. Adverse events were similar in the two groups (P = 0.117). Fungal cultures became negative in 92.3% of the sertaconazole group as compared to 80% in the amorolfine group (P = 0.010). LIMITATIONS: Antifungal susceptibility testing could not be done. CONCLUSION: Sertaconazole 2% is superior to amorolfine 0.25%, both in terms of effectiveness and tolerability. Improvement can be appreciated from second week onwards.

Anatomy and Applications of the #15 Scalpel Blade and Its Variations.

Scalpels have been used to make skin incisions since the advent of "modern" dermatosurgery. #15 Scalpel blade and #3 handle (Bard-Parker handle) are most frequently used by a dermatosurgeon. Besides the proper equipment, appropriate technique is mandatory to ensure a "precise" incision. In this article, we discuss about the anatomy, variations, and different uses of the #15 scalpel blade and the ideal method of making a "precise" skin incision.

Immunotherapy in viral warts with intradermal Bacillus Calmette-Guerin vaccine versus intradermal tuberculin purified protein derivative: A double-blind, randomized controlled trial comparing effectiveness and safety in a tertiary care center in Eastern India.

BACKGROUND: Current therapeutic modalities for viral warts are mostly ablative and are limited by high recurrence rates besides being unsuitable for numerous lesions. Immunotherapy has the potential to overcome these limitations. AIMS: The aim of this study was to compare the effectiveness and safety of Bacillus Calmette-Guerin vaccine versus tuberculin purified protein derivative in the immunotherapy of warts. METHODS: Patients received three doses of 0.1 ml of Bacillus Calmette-Guerin vaccine or tuberculin purified protein derivative intradermally over the deltoid region at 4-weekly intervals. They were followed-up for another month. Number of warts, complete cure rates and quality of life were assessed. RESULTS: A total of 60 patients were included. Complete clearance was noted in 16 (48.5%) out of 33 patients in the Bacillus Calmette-Guerin group and in 5 (18.5%) out of 27 in the tuberculin purified protein derivative group (P = 0.121). The number of lesions reduced statistically significantly from baseline in both the groups (P < 0.001) from the first follow-up visit onward (P < 0.05). The reduction was statistically significantly more in the Bacillus Calmette-Guerin group than in the tuberculin purified protein derivative group from the second follow-up onward. Dermatologic life quality index improved statistically significantly with both treatments. Adverse events (pain during injection, abscess formation and scarring at injection site) were more frequent with Bacillus Calmette-Guerin. No recurrence was seen after lesions cleared. LIMITATIONS: Patients were not followed up for more than 4 weeks after treatment. We could not estimate the cytokine levels or the peripheral blood mononuclear cell proliferation in response to Bacillus Calmette-Guerin/tuberculin purified protein derivative injections. CONCLUSION: Both intradermal Bacillus Calmette-Guerin and tuberculin purified protein derivative hold promise in the treatment of viral warts. Bacillus Calmette-Guerin may be more effective, though it had more adverse events in our study.

Loeffler's Syndrome Following Cutaneous Larva Migrans: An Uncommon Sequel.

Cutaneous larva migrans (CLM) is characterized by the formation of distinctive, tortuous, and serpentine skin lesions occurring as a result of epidermal burrowing by certain helminthic larvae. Although this condition is usually uneventful, rarely it may result in patchy pulmonary infiltration with peripheral eosinophilia, also called Loeffler's syndrome. This association is fairly uncommon and is thus being reported.

Unilateral, Linear Blue Rubber Bleb Nevus Syndrome (Bean's syndrome): An Unfamiliar Presentation: First Case from India.

Blue rubber bleb nevus syndrome (BRBNS) also called Bean's syndrome is a rare disorder characterized by multiple cutaneous venous malformations in association with visceral lesions, most commonly affecting the gastrointestinal tract. We report here, a 21-year-old woman patient, who presented with unilateral, blaschkoid distribution of cutaneous venous malformations along with blue rubber bleb nevus and recurrent episodes of hematochezia due to vascular lesions in the sigmoid colon; likely to be a case of BRBNS. The unusual unilateral, blaschkoid distribution of BRBNS prompted this present report.