The use of antibiotics, isotretinoin or hormonal regimens, according to the case, are the most relevant systemic treatments. Other treatment modalities are discussed below.
Oral prednisone 0.5-1.0 mg/kg daily should be prescribed to patients with severe inflammatory acne vulga-ris, acne fulminans and pyoderma faciale. Prednisone must be administered for 4-6 weeks and then reduced gradually. In acne fulminans and pyoderma faciale it is preferable to prescribe the steroids for 3-4 weeks before prescribing the isotretinoin. Similar oral doses are also indicated in patients whose acne flares badly while taking isotretinoin . Many times the worsening of acne observed between the third and the sixth week may be very severe and even trigger genuine manifestations of acne fulminans, although they should, more appropriately, be called 'pseudo' acne fulminans, since systemic features are minimal or almost absent and no pyrexia is noted. Baseline hematology and biochemistry parameters are within normal ranges. As this was observed in our department in 18 of 590 patients between 1983 and 1990, we decided to use isotretinoin and corticosteroids simultaneously and from the beginning in the very inflammatory and severe acne. An example of dosage according to body weight (i.e. 80 kg) is as follows:
We started with an initial isotretinoin dose of 20 mg/ day for a week, with slow dosage increases until the desirable dose of 1 mg/kg/day was reached in the 6th week, amounting to a total accumulated dose of 150 mg/kg/day. We preferred methylprednisone at a starting dose of 40 mg every other day for 6 weeks and progressively decreased the dose until total withdrawal of the corticoste-roid in the 10th week, leaving isotretinoin as sole course of therapy (fig. 1). The aim behind this therapeutic scheme, over the period of isotretinoin pharmacologic impregnation, is to avoid the early exacerbation phenomenon that would be triggered by an antigen-antibody reaction. There is altered immunological reaction to Propioni-bacterium acnes in some patients, with previous demonstration of both type III and IV hypersensitivity to this organism. Another theory is that altered neutrophil function may result in severe acne flares. P. acnes destruction is thought to result in mediator, inducing neutrophil che-motaxis, which may be responsible for flares seen on treatment with isotretinoin. Patients developing severe flares of the disease may be showing an exaggeration of this response . It has also been suggested that increased fragility of the pilosebaceous duct is induced by isotretinoin, leading to a massive contact with P. acnes antigens . Since we routinely implemented the simultaneous use of isotretinoin and corticosteroids for the most severe inflammatory acne (nodules, abscesses, cysts), we have no longer observed this horrendous manifestation. Therefore, we conclude that this combination prevents the development of 'pseudo' acne fulminans as a complication derived from the use of isotretinoin.
Zinc sulfate appears to have little treatment efficacy. Some authors have demonstrated in a double-blind trial that zinc sulfate capsules, 220 mg/day, corresponding to 50 mg of elemental zinc three times daily with food, may be beneficial to selected patients with mild-to-moderate pustular acne. However, these authors are reluctant to recommend oral zinc sulfate as treatment for acne vulgaris because of the high incidence of gastrointestinal side effects. They consider that the incidence of nausea would have been lower had they used gluconate zinc 200 mg/day rather than zinc sulfate .
As inflammatory acne lesions are infiltrated with neutrophils, the use of anti-inflammatory drugs (NSAIDs) was suggested and ibuprofen was selected for its properties. Effectively, ibuprofen decreases inflammation by inhibiting cyclooxygenase, a pivotal enzyme in the arachi-donic acid cascade leading to the formation of the proinflammatory prostaglandin products. Thus, ibuprofen may inhibit human leukocyte chemotaxis and the formation of the inflammatory lesions in acne. A study demonstrated that tetracycline hydrochloride capsules (1,000 mg/day) associated with ibuprofen tablets (2,400 mg/day) is effective when administered for 2 months to patients with moderately severe acne . Other authors combine minocycline capsules (150 mg/day) and ibuprofen tablets (1,200 mg/day) with excellent clinical response and the additional benefit of fewer side effects at low ibuprofen doses.
Dapsone (diaminodiphenylsulfone or DDS), effectively tested on lepra, was shown to possess anti-inflammatory activity for various dermatological diseases, primarily dermatitis herpetiformis in the early 1950s and subcorneal pustular dermatosis in 1956. The sulfones have been widely used to treat other dermatological conditions including bullous diseases, vasculitis, neutrophilic dermatoses, pilosebaceous diseases, infectious diseases, as well as pustular psoriasis and relapsing polychondritis. Dap-sone has been reported to be effective in the management of nodulocystic acne, but the few studies available are based on a limited number of cases [18, 19]. In 1974, we examined 484 patients treated with oral DDS. Patients with acne characterized by papules, pustules and occasional cysts accompanied by inflammatory lesions, did not respond to the medication, although, in some, there was a slight improvement not comparable with the one obtained with tetracycline, in view of which DDS was discontinued. The cystic, tuberous and phlegmonous acne cases, as well as the very severe manifestations thereof, improved markedly when treated with DDS at a dosage of 50-100 mg daily for 3 months. The condition gradually subsided until remission, with only a few low-intensity relapses . At present, DDS has undoubtedly been replaced by isotretinoin. However, due to its affordable cost, DDS is more advisable to be used in emerging countries. Dapsone use must be concomitant with the knowledge of its side effects. Some of them are pharmacological and predictable, but there are allergic and idiosyncratic reactions as well. Most patients with a deficiency of glu cose-6 phosphate dehydrogenase (G6PD) tolerate this drug well, except when very high dosages are used. Follow-up examinations and laboratory testing should be performed according to the monitoring guidelines. A complete blood count, a chemistry profile, a urinalysis and analysis of the G6DP levels should be included .
This drug has both antimicrobial and anti-inflammatory activity. The exact mechanism of clofazimine action is unknown, but the primary sites of action appear to be the neutrophil and the monocyte. As both cystic acne and acne fulminans may present granulomatous components, clofazimine was found to be effective in cases of recurrence after several courses of isotretinoin . At a dosage of 200 mg three times weekly, it has been used successfully in the treatment of acne fulminans . Finally, clofa-zimine has been shown to be of value in the treatment of solid facial edema, which is an exceptionally rare complication of acne .
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