As with other anti-inflammatory agents used to treat pemphigus, tetracycline is reportedly effective in patients with mild disease and offers a lower toxicity and broader safety profile than immunosuppressive agents. Calebotta et al.41 conducted the only controlled study of tetracycline. Twenty patients were enrolled in the study. Thirteen prospective patients received tetracycline 2 g/day and prednisone 0-5-1-0mg/ kg/day. The seven historical controls, all of whom had been treated with prednisone and azathioprine, were chosen at random. The duration of therapy before new blister formation ceased was significantly less in the treatment group (5-5 days versus 23 days). Interestingly, patients in the control group began the study with significantly higher dosages of prednisone and were unable to taper the dose as early as the patients in the treatment group. It is not clear whether this indicated a significant steroid-sparing effect, or whether patients in the treatment group had less severe disease. The range of disease severity was said to be similar in each group, but no objective criteria were reported. Regardless, the study suggested that the combination of tetracycline and steroid achieved more rapid control of disease than the combination of azathioprine and steroid. One patient in the experimental group discontinued the study because of sepsis and another because of gastrointestinal upset.
In another study by Alpsoy et al.,42 15 patients with pemphigus were treated with tetracycline and nicotinamide therapy. Almost half of the patients responded to the treatment. Thus, tetracycline (with or without nicotinamide), like dapsone, may be effective as monotherapy for a few select patients, thereby eliminating the need for steroids. Future studies may identify specific serological or molecular characteristics that distinguish responders.
Although the controlled study of tetracycline seems to suggest that more rapid control of disease can be achieved using tetracycline, when taken together, the evidence to support the efficacy of anti-inflammatory therapy is not substantial. The validity of historical controls is uncertain and the question remains whether the beneficial effects observed in patients treated with steroids and an adjuvant agent are the result of the adjuvant agent or are, in fact, due to the steroids. Anti-inflammatory agents such as dapsone and tetracycline may be of benefit in the treatment of mild cases of pemphigus or in the maintenance phase in steroid-dependent patients. However, large prospective controlled trials are necessary to recommend their use unequivocally.
Mycophenolate mofetil is an immunosuppressive drug recently introduced for use in preventing transplant rejection. Its potential usefulness in treating autoimmune or inflammatory skin conditions has generated much excitement, due in large part to its relatively minimal side-effects. A few small case series report on the treatment of pemphigus with mycophenolate. The largest series, reported by Enk and Knop,43 described 12 patients with pemphigus vulgaris who received combination therapy with prednisone and mycophenolate. All patients had relapsed while being treated with prednisone and azathioprine. Disease severity was not reported. Patients initially received prednisone 2 mg/kg/day and mycophenolate 2 g/day. All but one patient improved, and in all responding patients the prednisone dose was reduced to at least 5 mg/day by the end of the study. However, all patients relapsed when steroid doses were tapered during the 12-month study. Thus, patients relapsed while taking mycophenolate, as they had done when they were taking azathioprine. Serum titres of pemphigus autoantibodies fell precipitously during the study to less than a half of their pretreatment level within a month, and all titres were undetectable by 2 months. Nearly all patients developed lymphopenia, but side-effects were not serious and there were no deaths.
There are two other case series of five patients each. Very little patient history, methods, and data are reported in either series. In the series by Enk and Knop,44 patients enrolled in the study were described as having relapsed while taking azathioprine in the past. In the series by Nousari et al.45 four of the five patients had experienced azathioprine-induced side-effects in the past. The patients in both series recieved prednisone, high dose in one study, in combination with mycophenolate. All patients responded to treatment, with partial remissions reported at the end of the follow up period (lasting 9 months44 and >5 months,45 respectively). Aside from
Does mycophenolate mofetil, alone or in combination with corticosteroids, effectively reduce symptoms and induce remission in patients with pemphigus vulgaris?
lymphopenia and diarrhoea, no side-effects were reported.
The favourable results in each study are encouraging, and the prospect of a new and highly effective immunosuppressive agent is exciting, but so far no data indicate that mycophenolate plus prednisone is more effective than prednisone alone. Most patients in the studies either received very high-dose steroids, which may have been responsible for the observed improvement, or had mild disease that may have been responsive to lower doses of steroids. Thus, it is not surprising that most patients in the studies improved. In addition, the very rapid clinical and serological improvement, within a month, described by Enk and Knop43 has been questioned. Other investigators found that at least 8 weeks' treatment was necessary to observe such serological improvement.45 Regardless, further study of this interesting new drug is needed before it can be recommended as effective treatment for pemphigus.
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