Effectiveness and safety analysis of rituximab in 146 Indian pemphigus patients: A retrospective single-center review of up to 68 months follow-up.

BACKGROUND: Rituximab is being increasingly used for the treatment of pemphigus. Data derived from single-center studies following a uniform treatment protocol are limited. Effect of demography and disease type on treatment response is poorly characterized. OBJECTIVE: Our aim was to assess the effectiveness of biosimilar rituximab in pemphigus patients who had received rituximab as per rheumatoid arthritis protocol (2 doses, 1g each, infused 14 days apart). METHODS: It was a retrospective review of 146 eligible patients to assess the proportion of patients achieving complete remission off treatment, time to achieve complete remission off treatment, proportion of patients who relapsed after achieving complete remission off treatment, time taken to relapse, duration and total cumulative dose of corticosteroids administered after rituximab. Additionally, we tried to find whether a correlation existed between age, gender, total duration of illness before rituximab and pemphigus disease type with the above-mentioned outcome measures. RESULTS: Of 146 patients, 107 (73.3%) attained complete remission off treatment. Mean interval between first dose rituximab administration and complete remission off treatment was 6.6 ± 3.4months. Complete remission off treatment was sustained for a mean duration of 9.1 ± 8.5 months before relapse. Over a mean follow-up duration of 24.9 ± 17.1 months (median 23, maximum 68 months), 75 of 107 patients (76.5%) who had achieved complete remission after first cycle of rituximab relapsed. A mean total cumulative dose of 3496 ± 2496 mg prednisolone was prescribed over a mean duration of 7.2 ± 4.7 months after first cycle of rituximab. Time taken to achieve remission was significantly longer in pemphigus foliaceus and these patients required significantly higher cumulative dose of prednisolone over a longer duration after rituximab. No deaths and long-term complications were recorded. LIMITATIONS: Only clinical parameters were assessed. Immunological parameters including B-cell counts and enzyme-linked immunosorbent assay for anti-desmoglein antibody titers were not carried out. CONCLUSION: This study reinforces the beneficial role of rituximab in pemphigus. Pemphigus foliaceus patients required a higher total cumulative dose of prednisolone over a longer time to achieve remission and the remission lasted longer than that in pemphigus vulgaris.

Psoriasiform Pemphigus Foliaceus in an African American Female: An Important Clinical Manifestation.

A 50-year-old African-American woman presented to the dermatology clinic with a pruritic eruption of 3 years' duration. On clinical examination, the patient had well-demarcated, pink, atrophic plaques and superficial erosions over the inframammary folds and mid-chest. She also had well-demarcated, hyperpigmented, hyperkeratotic scaly plaques over the abdomen, suprapubic region, elbows, knees, and back with sporadic small superficial blisters. A punch biopsy of the right abdomen was performed and revealed psoriasiform epidermal hyperplasia, focal parakeratosis, and acantholysis throughout the superficial spinous and granular layers. Only a sparse inflammatory infiltrate was present in the underlying dermis. Clinical and histological findings supported the diagnosis of pemphigus foliaceus (PF), but psoriasis was included in the differential diagnosis due to the presence of discrete plaques with an erythematous border. We hypothesize that patients with psoriasiform presentations of PF may be misdiagnosed with plaque psoriasis. It is important to distinguish between PF and psoriasis as there is evidence that ultraviolet light, a common treatment for psoriasis, may exacerbate PF. We document and highlight this atypical psoriasiform presentation of PF in a patient with skin of color to raise awareness and improve diagnosis and outcomes.

J Drugs Dermatol. 2018;17(4):471-473.

Clinical, immunological profile and follow up of patients with pemphigus: A study from India.

BACKGROUND: Pemphigus has a protracted course and multiple factors influence its prognosis. The objective of this study was to describe the epidemiology and clinical profile of pemphigus patients and to study its influence on treatment end points. METHODS: : This was a retrospective chart review done in an Indian tertiary care hospital from December 1991 to December 2013. Patients with less than 3 months' follow up and those who had paraneoplastic pemphigus were excluded. RESULTS: : There were 132 patients with pemphigus, of which 118 (89.4%) had pemphigus vulgaris and 14 (10.6%) had pemphigus foliaceous. The time to disease control (TDC) was available for 100 patients (n = 100, 75.7%); patients with a minimum follow up of 3 months (n = 80) were included for studying the end points like time to first disease remission (TDR) and time to first disease relapse (TDRe). The median period of follow up was 23 months (range 3-245). Out of the 100 patients, 61.9% were on oral steroids with adjuvant therapy. The steroid dose required for disease control for n = 100, ranged from 0.2 to 1.5 mg/kg body weight. Of these, 60% were treated with steroid dose of 1 mg/kg, 22% with >1 mg/kg, and 18% with <1 mg/kg. The mean time to disease control (in months) in the group which received <1 mg/kg steroid was 1.02 ± 0.68, 1 mg/kg was 0.72 ± 0.51, and >1 mg/kg was 1.02 ± 0.62 (P = 0.017); with a significant difference between the groups 2 and 3 (P = 0.007), implying a faster disease control in those who received 1 mg/kg dose. This difference was significant after adjusting for the steroid sparing drugs taken at baseline (P = 0.009, C.I. - 1.44-13.59). The mean time to first disease remission (TDR) was 11.46 ± 2.06 months. Out of the 80 patients with a minimum follow up of 3 months, 75% had achieved either partial or complete remission. None of the other epidemiological, clinical or immunological parameters had an impact on the TDC or TDR. CONCLUSIONS: The epidemiological, clinical or immunological parameters had no impact on the treatment end points like time to disease control and time to first disease remission. The dose of steroids required for disease control higher than 1 mg/kg offered no advantage in the time to disease control as compared to 1 mg/kg. LIMITATIONS: The study was retrospective and disease severity scores were not applied. In view of the shorter follow up period, long term prognostic end points and mortality could not be well represented. The median period of follow up was 23 months. The serum anti- desmoglein antibody titres were not available at various treatment end points for correlation at different time intervals.

Urocytological evaluation of pemphigus patients on long term cyclophosphamide therapy: A cross sectional study.

BACKGROUND: Cyclophosphamide therapy is associated with several urological complications including urinary bladder malignancy. Data on urologic complications of chronic cyclophosphamide therapy for dermatologic conditions is not available. OBJECTIVES: To study the urocytological profile of pemphigus patients on long-term cyclophosphamide therapy. MATERIALS AND METHODS: In a cross-sectional study, consecutive patients who had received cyclophosphamide therapy for pemphigus for more than 12 months were included. All patients were subjected to urinalysis including microscopy, culture, and urine cytology. Immunocytochemical staining for cytokeratin 20 (CK-20) on urine sediments and ELISA (enzyme-linked immunosorbent assay) for nuclear membrane protein-22 (NMP-22) were performed in all cases. In patients with urinary symptoms, microscopic hematuria, or those detected with abnormal urine sediment cytology, NMP-22, and CK-20 positivity, cystoscopy, and other relevant investigations were also done. RESULTS: A total of 44 patients (43 of pemphigus vulgaris and one of pemphigus foliaceus) were recruited. Mean duration of cyclophosphamide intake was 2.9 ± 1.7 years (range 1-8 years) with a mean cumulative dose of 53 ± 28.4 g (range 6.5-141 g). Twenty-one cases (47.7%) each were asymptomatic and symptomatic with episodic urinary symptoms [of which two had urinary tract infection (UTI)] and two patients had gross hematuria. Urine cytology revealed mild urothelial nucleomegaly with hyperchromasia in four patients. However, CK-20 and NMP-22 were negative in all samples. Cystoscopy was performed in 21 cases and did not reveal any sign of bladder malignancy. LIMITATIONS: A relatively small sample size and lack of long-term follow-up were limitations. CONCLUSIONS: In our study, no serious urologic complications were found in pemphigus cases on chronic cyclophosphamide therapy.

Low-dose rituximab as an adjuvant therapy in pemphigus.

BACKGROUND: Pemphigus is a chronic autoimmune blistering disease where systemic steroids and immunosuppressants are the mainstay of therapy, but long-term treatment with these agents is associated with many side effects. Rituximab, a chimeric monoclonal anti-CD20 antibody, in low doses has shown efficacy as an adjuvant to reduce the dose of steroids. AIM: To study the clinical efficacy and safety of low-dose rituximab as an adjuvant therapy in pemphigus. METHODS: Fifty patients with extensive pemphigus were selected, who either had recalcitrant pemphigus, were steroid dependent, had relapsed after pulse therapy, had anti-desmoglein levels >20, had contraindications to conventional treatment or wanted to avoid conventional treatment and its side effects. Two doses of rituximab (500 mg) were given 2 weeks apart and patients were regularly followed up every 2 weeks for 3 months and then monthly upto 2 years. Complete blood counts, liver function tests, renal function tests, skin biopsy, direct immunofluorescence and desmoglein levels were checked before and after rituximab administration. Pre-rituximab chest X-ray and electrocardiograph were also obtained. RESULTS: At 3 months, 41 (82%) patients showed complete remission. Nine (18%) patients had partial remission. After 6-12 months, 20 (40% of enrolled patients) continued to be in remission and were off all systemic therapy and the remaining 19 (38%) were continuing to take low doses of steroids with or without other adjuvant immunosuppressants and 2 (4%) had to be given another 2 doses of rituximab and subsequently could be managed with low-dose steroids. Of the 9 patients in partial remission at 3 months, after 6-12 months 5 (10% of the total) were completely off treatment and went into complete remission and 4 (8%) were on additional treatment out of which 2 (4%) had to be given 2 additional doses of rituximab and were in partial remission with low-dose therapy at the end of 12 months. One patient developed urticaria as a side effect. Another developed herpes zoster. CONCLUSION: Our results show that low-dose rituximab is a well-tolerated and beneficial adjuvant therapy in recalcitrant pemphigus which helps reduce both the severity of disease as well as the dose of steroids and immunosuppressants.

Clinical efficacy of rituximab in the treatment of pemphigus: A retrospective study.

BACKGROUND: Pulsed corticosteroids have been used successfully for the management of pemphigus. However, prolonged use of glucocorticoids may be associated with adverse effects and some patients show a poor response to conventional therapy. Biologics have shown a promising role in such cases; however, there is limited data from the Indian subcontinent. OBJECTIVE: The primary objective was to assess the efficacy and adverse effects of rituximab in pemphigus. The secondary objective was to measure the cumulative doses of corticosteroids required for these patients. METHODS: We undertook a retrospective review of records of 25 pemphigus patients (pemphigus vulgaris: 21, pemphigus foliaceus: 4) who had received rituximab infusion (rheumatoid arthritis protocol in 21 patients, modified in 4). Oral prednisolone was administered in dosages up to 0.5 mg/kg of body weight and tapered over the next 3-4 months according to the disease activity. However, other immunosuppressive agents such as cyclophosphamide and azathioprine were continued for one year after clinical remission was achieved. RESULTS: Complete remission was observed in 22 (88%) patients. The mean time to disease control and complete remission was 1.10 and 4.36 months, respectively. Four (16%) patients experienced relapse after a mean duration of 11.75 months. The mean total dose of oral steroids administered was equivalent to 3535.64 mg of prednisolone. Exacerbation of disease was noted in two patients after the first dose of rituximab and infectious complications, pneumonia and cellulitis, developed in one patient each. LIMITATIONS: A small sample size, the retrospective nature of the study and unavailability of follow-up anti-desmoglein autoantibodies levels were limitations. CONCLUSION: Rituximab is an effective agent in the treatment of pemphigus. The use of rituximab enabled use of a lower initial dose of oral prednisolone in pemphigus and hence reduced its total cumulative dose. Severe side effects were rare.

Pemphigus in North-Western Yemen: A therapeutic study of 75 cases.

BACKGROUND: The incidence of pemphigus, though not documented, seems to be quite high in Yemen. There is no universal consensus on the treatment of this disease. AIMS: The aim was to evaluate the efficacy and side effects of different therapeutic regimens used in patients of pemphigus in North-Western Yemen. PATIENTS AND METHODS: Seventy-five Yemeni patients (39 males and 36 females) were included. Diagnosis was based on clinical features, histopathology and the Tzanck test. Results of treatment with these different therapeutic regimens were compared: (1) dexamethasone-cyclophosphamide pulse (DCP), (2) dexamethasone pulse with oral azathioprine, (3) oral prednisolone with azathioprine, (4) oral prednisolone with oral cyclophosphamide, and (5) prednisolone monotherapy. RESULTS: Pemphigus vulgaris (PV) was diagnosed in 46 patients, pemphigus foliaceus (PF) in 23, pemphigus vegetans (PVEG) in 5 and pemphigus herpetiformis (PH) in one. Among the 16 patients who received regular DCP therapy, 13 were in remission for 6 months to 11 years without medications (phase 4). Remission without pharmacotherapy could not be achieved with the other regimens and steroid-induced side-effects appeared to be more than with DCP. LIMITATIONS: Immunofluorescence was not available to confirm the diagnosis of pemphigus. Randomization was not done. CONCLUSION: The DCP regimen seemed to be superior to the other regimens used.

Use of rituximab in pemphigus patients with chronic viral hepatitis: report of three cases.

Use of rituximab in patients with chronic viral hepatitis can worsen pre-existing hepatitis or reactivate occult infection. There are no reports of use of rituximab in pemphigus patients with co-existing viral hepatitis. Herein, we report three pemphigus patients with co-existing chronic viral hepatitis (hepatitis C (n = 2), hepatitis B (n = 1)), who were treated successfully with rituximab under close supervision and concurrent antiviral drug administration. There was no derangement of the liver function tests or increase in viral load in any of the patients. By incorporating good collaboration with a hepatologist and close follow-up, such patients can be managed successfully with biologic therapies when the conventional treatment modalities have failed.