Efficacy and Safety of Cyclophosphamide, Azathioprine, and Cyclosporine (Ciclosporin) as Adjuvant Drugs in Pemphigus Vulgaris

Background:Pemphigus vulgaris is a potentially life-threatening, autoimmune bullous disease of the skin and mucous membranes. Most commonly, the disease is treated with prednisone in combination with an immunosuppressant agent, frequently referred to as adjuvant drug. However, there is no consensus regarding the first-choice adjuvant drug for the treatment of pemphigus vulgaris or the recommended dosage. Objective:To evaluate the efficacy and safety of prednisone as monotherapy and in combination with the three most popular adjuvant agents — azathioprine, cyclosporine (ciclosporin), and cyclophosphamide in the treatment of pemphigus vulgaris time to immunologic remission (non-detectable circulating pemphigus vulgaris antibodies), proportion of patients who remained free of clinical relapse within 5 years after discontinuation of therapy, time from treatment discontinuation until first relapse, and incidence of adverse effects. Results:The average (± SD) time to clinical remission was 7.2 ± 13.1 months in patients who received prednisone monotherapy, 6.8 ± 10.5 months in patients receiving additional azathioprine, 8.1 ± 11.8 months in the cyclosporine group, and 4.9 ± 6.9 months (which was significantly shorter than all other treatment groups, p < 0.05) in patients receiving cyclophosphamide. The average (± SD) times to immunologic remission were 33 ± 27 months, 28 ± 24 months, 30 ± 21 months, and 23 ± 17 months for prednisone monotherapy, azathioprine, cyclosporine, and cyclophosphamide, respectively. The proportions of patients who remained free of clinical relapse within 5 years after discontinuation of therapy were 55%, 50%, 43%, and 69% for prednisone monotherapy, azathioprine, cyclosporine, and cyclophosphamide, respectively. In patents who experienced relapse, the average (± SD) time from treatment discontinuation to clinical relapse was 10.50 ± 6.86 months in patients receiving prednisone monotherapy, 16.40 ± 17.36 months in the azathioprine group, 12.44 ± 6.48 months in the cyclosporine group, and 21.16 ± 20.13 months in the cyclophosphamide group. The safety profiles of all treatment regimens were comparable. Conclusion:Oral prednisone with cyclophosphamide is the most effective treatment for pemphigus vulgaris. All therapy regimens had a similar safety profile. In our opinion, cyclophosphamide at a dose of 1.1–1.5 mg/kg/day should be the adjuvant drug of choice in the treatment of moderate-to-severe pemphigus vulgaris.     

Klinik und Immunpathologie bei 48 Patienten mit Pemphigus

Background and Objective. Pemphigus is a rare intraepidermal autoimmune bullous disease. Two major variants, pemphigus vulgaris (PV) and pemphigus foliaceus (PF), are distinguished. The aim of this study was to document the clinical and immunpathological findings in all pemphigus patients who were diagnosed in the Department of Dermatology at the University of Würzburg over the past 10 years. Patients/Methods. Based on a retrospective study, clinical and immunpathological findings in 48 patients with pemphigus were recorded. All patients had positive findings by direct and/or indirect immunfluorescence microscopy. Results. Between January 1989 and August 1998, 48 patients were diagnosed with pemphigus at our institution; 31 patients had PV and 17 PF. The average age (±standard deviation) of PV patients was 55 (±17) and of PF patients 60 (±12) years. All PV patients showed involvement of mucous membranes and in 65% of cases, the skin was also involved. In contrast, PF patients had involvement only of the skin. By direct immunfluorescence microscopy, intercellular deposits of IgG and C3 were detected in 89% and 78% of PV cases, respectively. In PF, intercellular deposits of IgG were found in 94% and of C3 in 75% of cases. By indirect immunfluorescence microscopy on monkey esophagus, 94% of the PV and 88% of the PF patients revealed circulating serum antibodies. In 30 patients, we characterized the immune response by ELISA using recombinant desmoglein 1 and 3. All PF sera showed autoantibodies against desmoglein 1 and all PV sera against desmoglein 3. In PV with both mucous membrane and skin involvement, antibodies to both desmoglein 3 and 1 were detected. Conclusions. Our results confirm the correlation of the autoantibody profile with the clinical phenotype of pemphigus.     

Occult Herpes Simplex Virus Colonization of Bullous Dermatitides

Background: Acantholytic disorders, including pemphigus vulgaris, chronic benign familial pemphigus (Hailey-Hailey disease, superficial pemphigus), Darier disease, and Grover transient acantholytic dermatosis, as well as other vesiculo-bullous disorders, including bullous pemphigoid, epidermolysis bullosa, and atopic dermatitis, are prone to florid infections by herpes simplex virus (HSV)-I and -II, and, more rarely, by varicellazoster virus (VZV). As these infections are difficult to recognize clinically and histologically, their frequency remains unknown. A possible occult viral colonization has never been documented in these disorders. The manner in which the primary bullous disorders are contaminated by herpesviridae remains unclear. Objective: To retrospectively assess the possible presence of HSV and VZV in a series of biopsies of acantholytic disorders and bullous pemphigoid. Method: The typical α-herpesviridae-related cytopathic signs were searched for by conventional microscopy in skin biopsies of patients with bullous pemphigoid (n = 20), pemphigus vulgaris (n = 19), Darier disease (n = 18), chronic benign familial pemphigus (n = 3), and Grover transient acantholytic dermatosis (n = 3). Immunohistochemistry (IHC) targeted specific HSV-I, HSV-II, and VZV antigens. Polymerase chain reaction (PCR) was used for detecting HSV- and VZV-specific DNA sequences. Results: No cytopathic signs suggestive of HSV or VZV infection were detected. However, IHC revealed HSV antigens in Darier disease (1/18, HSV-I), Grover transient acantholytic dermatosis (1/3, HSV-I), pemphigus vulgaris (1/19, HSV-I), and bullous pemphigoid (2/20, HSV-I and HSV-II). In these IHC-positive cases, PCR amplified specific HSV primers in Darier disease (1/18), pemphigus vulgaris (1/19), and bullous pemphigoid (1/20). VZV antigens and nucleic acids were never identified. The HSV antigens were nearly always restricted to the upper part of the granular layer and thus differed from the usual HSV distribution during cutaneous infection. Negative and positive controls yielded consistently positive and negative results, respectively. Conclusion: This report shows for the first time that clinically and histologically occult HSV colonization may occur in Darier disease, Grover transient acantholytic disease, pemphigus vulgaris, and bullous pemphigoid. Given the frequent use of immunosuppressive treatments for primary bullous disorders, greater awareness of HSV colonization and infection is recommended in these patients.     

Adjuvant High-Dose Intravenous Immunoglobulin Therapy Can Be Easily and Safely Introduced as an Alternative Treatment in Patients with Severe Pemphigus Vulgaris

Background: Long-term corticosteroid therapy, often in association with other immunosuppressive agents, is considered the mainstay of pemphigus vulgaris (PV) therapy. Recent evidence has been changing this paradigm as patients who are non-responsive to conventional therapies or who experience severe adverse effects have been successfully treated with high-dose intravenous immunoglobulin (IVIg). However, the shift from conventional therapies to IVIg represents a major challenge in the daily practice of non-experienced clinicians because of potential adverse effects and other issues relevant to IVIg therapy such as the necessity for premedication, selection of cases, modality of infusion, patient monitoring, and the cost and length of hospital stay. Objective: The purpose of this preliminary study was to evaluate and report outcomes of treatment with IVIg in eight selected PV patients meeting clearly defined criteria for initiation of this therapy. Methods: Available guidelines for IVIg therapy in patients with autoimmune mucocutaneous blistering diseases were followed. Clinical response, induction and duration of remission, strategies for prevention of adverse effects, and total days of hospital stay in eight patients with severe PV treated with IVIg were retrospectively evaluated. Results: All patients had an effective clinical response without adverse reactions, leading to a significant corticosteroid-sparing effect. Conclusion: Our results indicate that, when current guidelines are followed, IVIg therapy can be easily and safely introduced as a treatment alternative in patients with severe PV. Careful monitoring of patients, utilization of a multidisciplinary approach, and evaluation of hospital-related issues can help the non-experienced clinician successfully manage patients with severe PV requiring IVIg therapy.     

Treatment of Pemphigus Vulgaris

Background: Pemphigus vulgaris is a rare, chronic, autoimmune mucocutaneous blistering disease. The disease can progress to involve the skin and multiple mucosae. Pemphigus vulgaris can be associated with a high morbidity and significant mortality rate. Treatment of the condition can be challenging. Conventional therapy primarily consists of systemic corticosteroids and immunosuppressant agents. In some patients with pemphigus vulgaris, these agents fail to provide an effective clinical response or have significant adverse effects. Methods: We evaluated data on 792 patients with pemphigus vulgaris retrieved from PubMed, covering the period 1973–2004. Only patients reported in the English literature were included in this review. Recently, several new therapeutic agents and treatment modalities have been described for the treatment of patients with pemphigus vulgaris. Some therapeutic agents that were used in the past and abandoned have recently regained favor. This review focuses on the therapeutic uses of dapsone, methotrexate, mycophenolate mofetil, chlorambucil, dexamethasone-cyclophosphamide pulse therapy, immunoablative therapy with cyclophosphamide, plasmapheresis, and extracorporeal photochemotherapy. Newer agents, such as intravenous immunoglobulin (IVIg) therapy and rituximab (an anti-CD20 chimeric monoclonal antibody), are also discussed. Results and conclusions: Among the oral agents, dapsone may be considered a first-line agent. This is primarily because the risk of potentially fatal adverse effects with this drug is lower than that associated with other available chemotherapeutic agents. In patients who are refractory to oral agents, alternative treatments have been used to prevent further disease progression. Recently, the use of IVIg therapy, with a defined protocol, has been reported to be beneficial. This therapy is promising since it may allow for discontinuation of all other therapies and is safe. The adverse effects from IVIg therapy are minimal. Furthermore, compared with other therapies, it provides a better quality of life.     

Dexamethasone-Cyclophosphamide Pulse Therapy in Pemphigus

Background: Autoimmune pemphigus is a group of severe blistering diseases. Although corticosteroids have dramatically altered the prognosis of pemphigus, morbidity and mortality resulting from the adverse effects of systemic corticosteroids remain high. Dexamethasone-cyclophosphamide pulse (DCP) therapy was introduced to diminish the adverse effects of prolonged conventional daily dose regimens. Objective: To report our experience with the use of the DCP regimen in patients with autoimmune pemphigus. Methods: In the period 1998–2002, 72 patients with various forms of autoimmune pemphigus treated with DCP therapy were included, of whom 36 patients were previously treated with conventional corticosteroid therapy, and 36 were newly diagnosed patients. Results: Of the 72 patients, 43 completed treatment, while 13 patients did not respond adequately to the treatment and continued with the conventional daily regimen, nine patients were lost to follow-up, and seven patients died. Two of these deaths were probably a consequence of DCP therapy. Conclusion: DCP regimen is a beneficial treatment for patients with pemphigus, sparing the adverse effects of conventional regimens.     

Variations in Serum Hemoglobin, Albumin, and Electrolytes in Patients Receiving Intravenous Immunoglobulin Therapy

Background and objective: Intravenous immunoglobulin (IVIg) is a solution of globulins containing antibodies derived from pooled human plasma of donors and used in the treatment of a number of immune deficiencies and autoimmune diseases. However, several investigators have reported biochemical alterations with use of IVIg. The objective of this study was to evaluate the effects of IVIg therapy on selected biochemical and hematologic parameters in patients with autoimmune mucocutaneous blistering diseases (AMBDs). Methods: In this preliminary clinical study, ten patients with AMBDs (seven with pemphigus vulgaris and three with mucous membrane pemphigoid) received 133 cycles of IVIg for a total of 399 infusions. We evaluated the effects of IVIg therapy on serum hemoglobin (Hb), albumin, and electrolyte levels, including sodium (Na⁺), potassium (K⁺), chloride (Cl^-) and calcium (Ca²⁺). Values of these parameters were measured 24 hours before, during, and 24 hours and 4 weeks after the 3-day infusion period. Results: The observed variations in serum electrolyte levels were physiologically and clinically negligible. Furthermore, 24 hours after the last infusion, mean electrolyte values had spontaneously returned to normal levels without the need for additional supplementation: Na⁺ 137.59 ± 1.42 mmol/L (p = 0.6091 vs baseline); K⁺ 3.97 ± 0.5 mmol/L (p = 0.2689); Cl^- 103.4 ± 2.69 mmol/L (p = 0.0388); and Ca²⁺ 9.07 ± 0.44 mg/dL (p = 0.5332). Conversely, significant variations in mean Hb and albumin levels were observed. When measured 24 hours after the last infusion, mild/moderate decreases in Hb (11.62 ± 2.12 g/dL; p = 0.009 vs baseline) and/or albumin (mean 3.14 ± 0.24 g/dL; p = 0.0016 vs baseline) were evident. Such changes may, albeit very rarely, be of sufficient clinical significance in individual patients as to necessitate additional treatment. Conclusion: In patients receiving intravenous IVIg for AMBDs, electrolyte values should be monitored but do not represent a real clinical threat. Hemoglobin and albumin values may be altered sufficiently to require additional treatment but this is a very rare occurrence. These findings confirm and extend previous reports of the safety of IVIg therapy.     

The demonstration of serum interleukin-8 and superoxide dismutase in Adamantiades-Behçet’s disease

Serum interleukin-8 (IL-8) production was measured in 43 Adamantiades-Behçet’s disease (A-BD) patients and in 46 healthy volunteers using a sandwich enzyme-linked immunosorbent assay (ELISA). The mean serum IL-8 level of the patients (14.6 ± 3 pg/ml) was significantly higher than that of controls (10.8 ± 3 pg/ml, P < 0.05). Since IL-8 is known to have proinflammatory properties, it may play some role in the pathogenesis of A-BD. We also investigated the activity of serum superoxide dismutase (SOD) in the 43 patients with A-BD and in the 46 healthy volunteers. Serum SOD activity was markedly increased in the patients with A-BD (13.1 ± 3%), especially in active A-BD, compared with that in the healthy volunteers (6.7 ± 3%, P < 0.01). Our results suggest the involvement of IL-8 and SOD in the pathogenesis of A-BD as seen in other inflammatory diseases.     

Therapeutic effect of mizoribine on pemphigus vulgaris and pemphigus foliaceus

We evaluated the effectiveness of mizoribine, a newly developed immunosuppressive agent, as an adjuvant therapy in the treatment of both pemphigus vulgaris and pemphigus foliaceus. Eleven pemphigus patients (eight pemphigus vulgaris and three pemphigus foliaceus) received the combination therapy of prednisolone and mizoribine. Complete remission was observed in three of the eight patients with pemphigus vulgaris and in one of the three patients with pemphigus foliaceus. The four patients with complete remission had a rapid clinical response and achieved remission at a median of 11.8 months. Partial remission was achieved in two of the three patients with pemphigus foliaceus. The median time to achieve partial remission was 16.0 months. Six (55.6%) of the 11 patients with pemphigus had complete or partial remission and were able to taper their prednisolone. The cumulative probability of having a complete remission was 64.3% at 19 months of follow-up using Kaplan-Meier analysis. The effectiveness of the additional mizoribine therapy could be attributed to its corticosteroid-sparing properties as well as its immunosuppressive effects. The serum concentration titer of mizoribine was around 1.0?μg/mL 2 hours after administration. Patients who were not improved by the additional mizoribine might require a continuously higher dose of mizoribine to achieve effective therapy.     

Verlaufsstabilisierung von Patienten mit fortgeschrittenen malignen Melanomen in Stadium IV durch Trofosfamidbehandlung

Background and Objective. Stage IV melanoma patients with progressive disease are a therapeutic challenge for every dermatologist. We wondered whether a mild oral chemotherapy with trofosfamide would ameliorate disease progression in these patients. Patients/Methods. 40 patients with melanoma (stage IV disease) were treated with 100 mg/day of trofosfamide for 6 months. All patients showed a progressive disease prior to this intervention. Results. One patient experienced a partial remission, 25 patients showed a stable disease. Only 11 patients were progressive under trofosfamide treatment. 7 patients died during the study period. Conclusions. Therapy with trofosfamide seems to ameliorate disease progression in stage IV patients.     

Psoriasis Therapy and Cardiovascular Risk Factors

Background: Psoriatic patients present with an increased frequency of cardiovascular events. Objective: To study the impact of psoriasis duration and therapy on traditional and new cardiovascular risk factors. Study Design: A longitudinal study performed between 2005 and the first trimester of 2008. Each patient was followed up for 12 weeks, and was observed before and 3, 6, and 12 weeks after starting therapy. Setting: Patients attending the Dermatology Service, University Hospital of Coimbra, Coimbra, Portugal were enrolled. Subjects: Thirty-four patients with psoriasis vulgaris and 37 healthy volunteers as controls. Main Outcome Measures: Psoriasis Area and Severity Index (PASI); lipid profile, oxidized low-density lipoprotein (oxLDL), oxLDL/low-density lipoprotein (LDL), total antioxidant status, lipid peroxidation, C-reactive protein (CRP), and circulating levels of adiponectin. Intervention: Ten patients started therapy with topical treatment, 11 with narrow-band UVB radiation (NB-UVB), and 13 with psolaren plus UVA (PUVA). Results: Before starting therapy, psoriatic patients presented with several risk changes in their lipid profiles, and significantly higher CRP, oxLDL, and oxLDL/LDL, and lower adiponectin levels (vs control subjects), which may further contribute to inflammation and atherogenesis. After treatment of the patients, although no significant differences were observed in the lipid profile compared with baseline, some changes suggested that the treatment could somehow alter lipid metabolism, as the reduction in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A and the increase in the atherogenic index cholesterol/HDL-C maintained an even higher significance (as shown by p-values) when compared with the control group. After topical therapy, there was a significant reduction in thiobarbituric acid reactivity only, suggesting that the reduction in the hyperproliferative process within the lesions is important for lipid peroxidation. After NB-UVB therapy, oxLDL/LDL, cholesterol/HDL-C, lipoprotein (a) [Lp(a)], and CRP remained higher than in the control subjects, reflecting persistent inflammation and atherogenic risk. After PUVA treatment, there was a significant reduction in Lp(a), associated with an almost significant increase in apolipoprotein-B (p = 0.054); these changes were not observed after NB-UVB treatment. However, after PUVA and NB-UVB treatment, CRP and, in the NB-UVB group, oxLDL/LDL were persistently higher than controls. Conclusion: Our data show that psoriatic patients present with several lipid profile changes that seem to be related to the severity of the disease and/or the treatment used. Mild psoriasis patients receiving topical treatment presented before starting therapy with a lipid profile similar to controls, whereas those undergoing NB-UVB and PUVA, who had higher PASI scores, presented with several risk factors. Moreover, PUVA therapy seems to interact in a different way with lipids that might result from an interaction of psoralen with plasma lipids, namely Lp(a). Inflammation, a hallmark of psoriasis, also seems to be related to psoriasis severity. Both NB-UVB and PUVA were effective, as shown by the reduction in PASI score, as well as in the oxidative and inflammatory stress markers. However, after NB-UVB and PUVA, a low-grade inflammatory process still persisted, which might be related to the duration of remission of the disease.     

Cost Effectiveness of Management of Mild-to-Moderate Atopic Dermatitis with 1% Pimecrolimus Cream in Children and Adolescents 2–17 Years of Age

Introduction: Atopic dermatitis (AD) has the potential to cause a long-term economic impact on patients, their families, and the healthcare system. Objective: To determine if 1% pimecrolimus cream is cost-effective in treating mild-to-moderate AD in patients 2–17 years of age. Methods: Data on the efficacy of AD management with 1% pimecrolimus cream (Elidel®, Novartis Pharma GmbH, Wehr, Germany) were obtained from a 12-month, randomized, double-blind, multinational, controlled clinical trial comparing pimecrolimus and conventional therapy. Markov modeling was used for the economic model, based on: (i) Investigators Global Assessment scores assessed at each visit during the clinical trial; (ii) estimated costs for medication and physician visits for each level of disease severity; and (iii) utility values for each level of disease severity. The perspective was that of a third-party payer. Results: In 2004 US dollars, the incremental cost-effectiveness of 1% pimecrolimus cream was $US38 231 per quality-adjusted life year (QALY) gained compared with conventional therapy. Sensitivity analyses showed a range of $US27 299 to $US63 457 per QALY gained. Conclusion: With an incremental cost-effectiveness ratio of <$US50 000 per QALY gained, 1% pimecrolimus cream offers a cost-effective therapeutic option in the management of AD.     

Long-term results of adjuvant chemotherapy after therapeutic lymph node dissection in patients with cutaneous malignant melanoma

Background and Objective. 224 patients with malignant melanoma and palpable axillary or inguinal lymphadenopathy underwent therapeutic lymph node dissection at the Martin-Luther-University in Halle, Germany. between 1983 and 1994. 120 received adjuvant chemotherapy; we evaluated the effects of various regimens in this group. Patients/Methods. Surgical treatment alone was performed in 104 patients. This group's results were compared to those of 94 patients who additionally received an adjuvant polychemotherapy [dacarbazine (DTIC), vincristine, 5-fluorouracil and hydroxyurea] and 26 patients who received either DTIC monotherapy or DTIC plus interferon-alfa. Results. The median follow-up was 88 months. The 5-year survival rates were 31.0±5% after surgery alone, 26.4±4% after adjuvant polychemotherapy and 27.0±9% after DTIC based chemotherapy. The three survival curves did not differ significantly. In a multifactorial analysis, the number of metastatic lymph nodes was the single significant predictor of survival after therapeutic lymph node dissection, whereas Breslow thickness, ulceration, site of the primary melanoma, age, sex and adjuvant therapy were not significant. Conclusion. No beneficial effect of adjuvant chemotherapies could be demonstrated.     

Treatment of Pemphigus Vulgaris and Pemphigus Foliaceus: A Systematic Review and Meta-Analysis

Background

No optimal therapeutic approach has been established for pemphigus.

Objective

Our objective was to evaluate the efficacy, steroid-sparing effect, and safety of available treatment modalities.

Methods

PubMed, LILACS (up to July 2014), the Cochrane Central Register of Controlled Trials (CENTRAL, issue 5 of 12, May 2014), and the ClinicalTrials.gov registry and reference lists were searched for randomized controlled trials of any treatment modality for pemphigus vulgaris and pemphigus foliaceus. Data were extracted independently by two authors using predefined appraisal criteria and data fields.

Results

A total of 20 studies (826 participants) were included. Most were small and open-labeled; all but seven were not concealed for allocation. Owing to the variability in intervention arms, five meta-analyses were performed, each pooling the data of two to three trials. Studies excluded from the meta-analyses were described quantitatively. Azathioprine had a steroid-sparing effect but did not increase remission rate. Mycophenolate mofetil induced sustained remission more quickly than did placebo and delayed time to relapse but did not have a steroid-sparing effect or favorable remission rate. Cyclophosphamide had a steroid-sparing effect, though less than azathioprine, but did not affect the remission rate or time-to-disease control. Intravenous immunoglobulin had more favorable short-term efficacy than did placebo. Topical epidermal growth factor hastened lesion healing.

Conclusions

Although some of the available therapeutic modalities for pemphigus are beneficial in terms of steroid-sparing, hastening response, or delaying relapse, none were found to increase the complete response rate compared with glucocorticoids alone, currently the mainstay of treatment. Multicenter randomized controlled trials and case control studies with uniform outcome measures are warranted.     

Serum prolidase activity in psoriasis patients

This study aimed to evaluate serum prolidase activity and the effects of gender, body mass index (BMI), disease severity and duration, and therapy type on prolidase activity in patients with psoriatic as well as the relationship between serum NO· and prolidase levels in these patients. The study included 29 clinically documented plaque patients with psoriasis and 24 healthy volunteers. Data such as age, sex, BMI, duration and severity of disease, and type of therapy were assessed. NO· levels were determined by the Griess reaction. Serum prolidase assay is based on a colorimetric determination of proline by Chinard’s reagent. We did not determine any difference in serum NO· levels of psoriatic patients when compared to controls. Serum prolidase levels in psoriasis patients were significantly higher than those in controls. There was no significant difference in prolidase activity between male and female. No statistically significant correlations were found between serum prolidase levels and BMI, PASI and disease duration. When compared between topical treatment group and systemic treatment group, there was no significant difference in serum prolidase activity. In conclusion, patients with psoriasis exhibit higher serum prolidase activity independent of gender, BMI, disease severity or duration, type of treatments or NO· level. However, further studies are needed to verify these findings as well as altered collagen synthesis in patients with psoriasis.     

Comparison of Azelaic Acid and Anthralin for the Therapy of Patchy Alopecia Areata

Background: Although topical azelaic acid has been previously used for the treatment of alopecia, no controlled trials of azelaic acid for this condition have been conducted to date. Objective: The goal of this study was to determine the efficacy, tolerability, and safety of azelaic acid treatment in patients with patchy alopecia areata (AA) in comparison with anthralin (dithranol) treatment. Subjects and methods: This study included 31 subjects with patchy AA who did not receive any treatment for at least 1 month prior to the study. Demographic and clinical characteristics of these subjects were recorded at baseline. Subjects were randomized to apply either 20% azelaic acid (15 subjects) or 0.5% anthralin (16 subjects) for 12 consecutive weeks. In a subsequent 8-week follow-up period no cream was applied. Two independent investigators performed an efficacy evaluation with clinical examination using a terminal hair regrowth score (RGS) with a scale ranging from 0 (inadequate response) to 2 (complete response) at week 20. Partial response was accepted as score 1. Results: Both groups were well matched for the relevant demographic and clinical indicators affecting treatment response at baseline. All subjects completed the trial. At week 20 the RGS was 1.27 ± 0.9 in the azelaic acid group versus 1.37 ± 0.8 in the anthralin group (p > 0.05). A complete response was observed in 53.3% of cases in the azelaic acid group (8 of 15) compared with 56.2% (9 of 16) in the anthralin group (p > 0.05). No serious adverse events were observed in either group during the study. Conclusion: The present pilot study showed that the use of azelaic acid gave similar results to anthralin with regard to hair regrowth, and that it can be an effective topical therapy for patchy AA. More extensive trials are necessary, however, to reach a definitive conclusion.     

Pharmacologic Interventions for Hidradenitis Suppurativa

Background: Hidradenitis suppurativa is a chronic debilitating skin disease that is recalcitrant to treatment. Objective: The aim of this article was to conduct an evidence-based review of pharmacologic interventions for the treatment of hidradenitis suppurativa (HS). Methods: A systematic search of MEDLINE, EMBASE, and the Cochrane database was conducted to identify controlled trials (randomized controlled trials, cohorts, and case-control studies) published in English. The abstracts were examined using predetermined inclusion and exclusion criteria. The identified studies were used to develop the recommendations. Clinically relevant outcomes that were assessed were: clinical remission, patient global assessment, physician global assessment, number of skin lesions, and improvement in Hurley’s stage, or Sartorius score. Results: Overall there was sparse evidence to support the use of any treatment modality. There is fair evidence to support the use of antibacterials in HS and they should be used as first-line therapy (level II-1/grade B). There is fair evidence to support the use of intravenous infliximab in the treatment of advanced HS (Hurley’s stage II and III). Given the high cost of anti-tumor necrosis factor therapy and its adverse-effect profile, intravenous infliximab should be offered to patients with severe disease affecting their daily activities who have failed antibacterial therapy (level I/grade B). There is insufficient evidence to support the use of antiandrogens in HS; consideration could be given to their use in women with mild to moderate disease (Hurley’s stage I and II) who have failed antibacterial therapy and women with an abnormal hormone profile (level II-2/grade I). Conclusions: The existing evidence suggests that antibacterials and anti-tumor necrosis factor therapy are effective in the treatment of HS. Further research is required to confirm the efficacy of the different medications within these groups and to explore the efficacy of other treatment modalities.     

Pemphigus vulgaris treated with adalimumab: case study

The study describes the case of a patient with a clinical and histopathological diagnosis of pemphigus vulgaris accompanied by severe side-effects of combined immunosuppressive therapy, who achieved a remission of the disease with adalimumab. Pemphigus vulgaris is a chronic blistering disease of the skin and mucous membranes. Before corticosteroids were introduced, mortality was high. Corticosteroids are currently used as first-line therapy. To reduce the dose of corticosteroids, therapeutic combinations with corticosteroid-sparing immunosuppressive agents are used. The therapy brings a number of complications due to its side effects. To achieve a remission of the disease by treating our patient with combined immunosuppressives, we administered adalimumab and achieved a very good clinical response.     

Severe Multi-Resistant Pemphigus vulgaris: prolonged remission with a single cycle of Rituximab

Pemphigus vulgaris is an autoimmune bullous disease whose therapy is based on systemic corticosteroids, with or without immunosuppressants. Rituximab is a chimeric monoclonal antibody of the IgG class, directed at a specific CD20 B cell surface antigen, used in pemphigus vulgaris empirically since 2002, with success in 90% of the cases and long periods of remission. Male patient, 33 years old, diagnosed with pemphigus vulgaris, confirmed by histopathology and direct immunofluorescence. He was treated for seven months with numerous treatments, including immunosuppressive drugs, with an unsatisfactory response, until he had complete remission with the use of rituximab. During a 34-month follow-up period, the patient presented a slight clinical relapse, which was successfully controlled with prednisone in a daily dose of 120mg, soon reduced to 20mg.     

Gold: an old drug still working in refractory pemphigus

BACKGROUND: The mainstay of treatment for pemphigus is systemic corticosteroids. Different adjuvants have been used to reduce side-effects of long-term corticotherapy. Gold is an anti-inflammatory drug used in autoimmune diseases, whose use has waned with the advent of new immunosuppressive agents. OBJECTIVE: To study the outcome of the use of intramuscular gold treatment of pemphigus vulgaris refractory to previous therapies. METHODS: Thirteen patients with pemphigus vulgaris who had failed to respond to several prior therapies were treated with aurothiomalate, as a steroid-sparing agent. Patients were monitored to assess disease activity and gold toxicity. RESULTS: Seven patients achieved complete remission. Four patients were able to taper prednisone doses, although pemphigus flared when prednisone was discontinued or reduced. Toxicity was observed in the other two patients. CONCLUSIONS: In 53.4% of the patients, the use of chrysotherapy resulted in the complete clearing of the disease, discontinuation of all systemic therapies and induced a long-term clinical remission. Prednisone doses were able to be reduced in the remaining 46.6%. Any side-effects were reversible with drug discontinuation. Gold therapy showed efficacy as a secondary line treatment in refractory pemphigus vulgaris.