Vogt-Koyanagi-Harada syndrome: a discussion about resistance to corticotherapy / Vogt-Koyanagi-Harada: uma discussão sobre resistência à corticoterapia

ABSTRACT Vogt-Koyanagi-Harada (VKH) syndrome is an inflammatory condition of unknown etiology that can affect the eye. The most common ocular manifestation related to VKH is bilateral diffuse uveitis associated to exudative retinal detachment. Although these patients respond well to steroid pulse therapy, we report a case of a 44-year-old female patient presenting bilateral exudative retinal detachment and clinical diagnosis of VKH, who did not respond to the first cycle of 3-day pulse therapy with methylprednisolone. The exudation was reabsorbed only after a second cycle of steroid therapy.

RESUMO A doença de Vogt-Koyanagi-Harada é inflamatória e de etiologia desconhecida, podendo afetar o olho. A manifestação ocular mais comum relacionada à doença de Vogt-Koyanagi-Harada é a uveíte difusa bilateral associada ao descolamento exsudativo da retina. Embora esses pacientes respondam bem à pulsoterapia com esteroides, relatamos um caso de paciente de 44 anos que apresentou descolamento exsudativo bilateral da retina com diagnóstico clínico de doença de Vogt-Koyanagi-Harada que não respondeu ao primeiro ciclo de pulsoterapia de 3 dias com metilprednisolona. A exsudação apenas reabsorveu após uma segunda rodada de terapia com esteroides.

Precordial pain, leukocytosis and bicytopenia in a teenager with systemic juvenile idiopathic arthritis under immunosuppressive therapy / Dor precordial, leucocitose e bicitopenia em adolescente com artrite idiopática juvenil sistêmica em terapia imunossupressora

ABSTRACT Objective: To highlight the importance of the new classification criteria for the macrophage activation syndrome (MAS) in systemic juvenile idiopathic arthritis in order to reduce morbidity and mortality outcome related to this disease. Case description: A 12-year-old female patient with diagnosis of systemic juvenile idiopathic arthritis under immunosuppression therapy for two years developed cough, acute precordial chest pain, tachypnea, tachycardia and hypoxemia for two days. Chest tomography showed bilateral laminar pleural effusion with bibasilar consolidation. The electrocardiogram was consistent with acute pericarditis and the echocardiogram showed no abnormalities. Laboratory exams revealed anemia, leukocytosis and increased erythrocyte sedimentation rate, as well as C-reactive protein rate and serum biomarkers indicative of myocardial injury. Systemic infection and/or active systemic juvenile idiopathic arthritis were considered. She was treated with antibiotics and glucocorticoids. However, 10 days later she developed active systemic disease (fever, evanescent rash and myopericarditis with signs of heart failure) associated with macrophage activation syndrome, according to the 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis. She was treated for five days with pulse therapy, using glucocorticoids, immunoglobulin and cyclosporine A, with improvement of all clinical signs and laboratory tests. Comments: Myopericarditis with signs of heart failure associated with MAS is a rare clinical presentation of systemic juvenile idiopathic arthritis. Macrophage activation syndrome occurs mainly during periods of active systemic juvenile idiopathic arthritis and may be triggered by infection. Knowledge about this syndrome is crucial to reduce morbidity and mortality.

RESUMO Objetivo: Destacar a importância do conhecimento sobre os novos critérios de classificação para síndrome de ativação macrofágica (SAM) na artrite idiopática juvenil sistêmica para reduzir a morbidade e mortalidade desse desfecho. Descrição do caso: Adolescente do sexo feminino de 12 anos de idade, em terapia imunossupressora por diagnóstico de artrite idiopática juvenil sistêmica há 2 anos, com quadro de tosse, dor precordial aguda, taquipneia, taquicardia e hipoxemia há 2 dias. A tomografia de tórax evidenciou efusão pleural laminar bilateral com consolidação bibasal. O eletrocardiograma foi compatível com pericardite aguda, e o ecocardiograma foi normal. Os exames laboratoriais revelaram anemia, leucocitose e aumento da velocidade de hemossedimentação, proteína C-reativa e marcadores séricos de lesão miocárdica. Infecção sistêmica e/ou doença sistêmica em atividade foram consideradas. A paciente foi tratada com antibióticos e glicocorticoide. Entretanto, dez dias depois, evoluiu com doença sistêmica em atividade (febre, exantema e miopericardite com insuficiência cardíaca) associada à SAM, de acordo com o 2016 Classification Criteria for Macrophage Activation Syndrome in Systemic Juvenile Idiopathic Arthritis, e necessitou de cinco dias de pulsoterapia com glicocorticoide, imunoglobulina e ciclosporina A, com melhora de todos os parâmetros clínicos e laboratoriais. Comentários: A miopericardite com sinais de insuficiência cardíaca associada à SAM é uma apresentação clínica rara da artrite idiopática juvenil sistêmica, que ocorre principalmente em períodos de atividade sistêmica da doença e pode ser deflagrada por infecções. O conhecimento sobre essa síndrome é fundamental para reduzir morbidade e mortalidade desse grave desfecho.

Comparative efficacy of continuous and pulse dose terbinafifine regimes in toenail dermatophytosis: A randomized double-blind trial.

Introduction: Dermatophytes are the most frequently implicated agents in toenail onychomycosis and oral terbinafi ne has shown the best cure rates in this condition. The pharmacokinetics of terbinafi ne favors its effi cacy in pulse dosing. Objectives: To compare the effi cacy of terbinafi ne in continuous and pulse dosing schedules in the treatment of toenail dermatophytosis. Methods: Seventy-six patients of potassium hydroxide (KOH) and culture positive dermatophyte toenail onychomycosis were randomly allocated to two treatment groups receiving either continuous terbinafi ne 250 mg daily for 12 weeks or 3 pulses of terbinafi ne (each of 500mg daily for a week) repeated every 4 weeks. Patients were followed up at 4, 8 and12 weeks during treatment and post-treatment at 24 weeks. At each visit, a KOH mount and culture were performed. In each patient, improvement in a target nail was assessed using a clinical score; total scores for all nails and global assessments by physician and patient were also recorded. Mycological, clinical and complete cure rates, clinical effectivity and treatment failure rates were then compared. Results: The declines in target nail and total scores from baseline were signifi cant at each follow-up visit in both the treatment groups. However, the inter-group difference was statistically insignifi cant. The same was true for global assessment indices, clinical effectivity as well as clinical, mycological, and complete cure rates. Limitations: The short follow-up in our study may have led to lower cure rates being recorded. Conclusion: Terbinafi ne in pulse dosing is as effective as continuous dosing in the treatment of dermatophyte toenail onychomycosis.

Weekly azathioprine pulse versus daily azathioprinein the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study.

Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP) are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the effi cacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92%) patients on WAP and 21 (96%) on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically signifi cant and comparable (P = 0.366). Patients on WAP had a higher incidence of adverse effects (P = 0.02). Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

Intravenous methylprednisolone pulse therapy in severe alopecia areata.

Background: Severe, extensive, therapy resistant alopecia areata represents a clinical challenge. Systemic corticosteroids are a therapeutic tool that still needs to be evaluated. Aim: The purpose of this study was to assess the efficacy and safety of methylprednisolone pulse therapy in alopecia areata and to find prognostic factors for a favourable outcome. Methods: A total of 32 patients with severe multifocal alopecia areata (more than 40% scalp hair loss), alopecia totalis, and alopecia universalis were treated with infusions of 500 mg methylprednisolone for 3 days every month for 3 consecutive months. The end point of the study was 12 months. Results: Of 32 patients, 26 (81.3%) reported a clinical response. Four patients (12.5%) showed complete hair regrowth, 6 patients (18.8%) showed >50% hair regrowth, ten (31.3%) had <50% hair regrowth, 6 (18.75%) were non responders, and another 6 patients (18.8%) had relapse after an initial regrowth. Multivariate analysis revealed that patients reporting at the first episode and those with multifocal disease had the best results. Conclusion: Methylprednisolone infusions represent a possible therapeutic option for patients with multifocal alopecia areata and those presenting with the first episode of the disease.

Monthly rifampicin, ofloxacin, and minocycline therapy for generalized and localized granuloma annulare.

Background: The localized form of granuloma annulare is usually self‑limiting, resolving within 2 years. Generalized granuloma annulare, on the other hand, runs a protracted course, with spontaneous resolution being rare. It is also characterized by a later age of onset, an increased incidence of diabetes mellitus, poor response to therapy, and an increased prevalence of HLA Bw35. Objective: To assess the efficacy of monthly pulsed rifampicin, ofloxacin, and minocycline (ROM) therapy in the management of granuloma annulare.Methods: Six biopsy proven patients of granuloma annulare were included in the study, five of the generalized variety, and one localized. Three of these patients were resistant to standard modalities of treatment. All six patients were treated with pulses of once monthly ROM till complete resolution of all lesions. Results were analyzed in terms of complete resolution of lesions and side effects. Presence of comorbid conditions was noted. Result: All six patients were successfully treated with 4-8 pulses of monthly ROM. None of the patients reported any adverse effects. Limitations: Small sample size and the lack of a control group are limitations. Conclusion: Treatment with pulses of once monthly ROM caused complete resolution of lesions in both localized and generalized granuloma annulare, even in cases recalcitrant to conventional therapy. There were no side effects in any of the patients. Larger trials are needed to substantiate the efficacy of monthly ROM in granuloma annulare.

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.