Overview of Sulfonamides and Related Medications: Query if Mesalamine should be Preferred Over Dapsone and Sulfasalazine

Sulfonamide research led to the discovery of dapsone and sulfasalzine. Both of these latter drugs have found a niche in the dermatological armamentarium especially for treatment of numerous non-infectious, inflammatory, autoimmune, and bullous disesases. These drugs, however, have side effects which include toxic hepatitis, neuropathy, cholestatic jaundice, hemolysis and methemoglobinemia. In the case of sulfasalamine, it is a conjugate of mesalamine and sulfapyridine. Of note, the latter moiety, sulfapyridine, is no longer available for human use as a separate drug due to side effects. In regards again with sulfasalazine, a pharmacology textbook credits mesalamine to be the major therapeutic moiety, while sulfapyridine is the culprit of the most significant adverse effects. There has been a suggestion in the literature that mesalamine may be the preferred agent for some of these dermatologic therapies for which Dapsone and sulfasalazine are presently suggested. A major impetus to seek this alternate therapy would be its more favorable side effect profile. Certainly more clinical studies using mesalamine are warranted to attest to its clinical effectiveness in relation to the two more established alternatives. Sulfonamides were developed in the 1930s and were the first effective antimicrobial agent for systemic administration. Sulfonamide research led to the discovery of related compounds, dapsone and sulfasalazine. As a rule, sulfonamides are bacteriostatic (not bacteriocidal), and rely on cellular and humoral host defenses for full eradication of a bacterial infection. Although it now occupies a relatively small place in the therapeutic armamentarium for infections, its usage has recently increased given its benefit in most cases of methicillin-resistant Staphylococcus aureus [1]. Its usage in dermatology may also increase given its effects on the Propionibacterium acnes biofilm [2]. The term ‘sulfonamide’ refers to chemical structures having the frame composed of para-aminobenzenesulfonamide. Their mechanism of action is competitive antagonist of dihydropteroate synthase, a bacterial enzyme responsible for incorporation of para-aminobenzoic acid for folic acid synthesis. Sulfonamides do not affect human cells by this mechanism, as they require preformed folic acid. Microorganisms which do not synthesize their own folic acid are also resistant to this antibiotic. Trimethoprim is a synergist of sulfonamides because this drug blocks a sequential enzyme in the same pathway by which organisms synthesize folic acid. Sulfonamides have been used with clinical success in some blistering diseases, but not to the extent of dapsone and sulfasalazine [3]. *Address correspondence to this author at the University of Toledo School of Medicine, 5600 Monroe Street, Suite 106B, Sylvania, OH 43560, USA; Tel: 419-885-3403; Fax: 419-885-3401; E-mail: [email protected] Dapsone is damino-diphenyl sulfate, which has a chemical structure very similar to sulfonamines. Like sulfonamines, its antibacterial properties are due to inhibiting folic acid synthesis. Although it is most often used in multidrug therapy for leprosy, it has numerous other applications. As an anti-infective agent, it is also utilized in the treatment of malaria and Pneumocystis carinii pneumonia. In dermatology, it has been found helpful in the treatment of numerous non-infectious, inflammatory, autoimmune, and bullous disesases [4]. The list of disorders reported to benefit with dapsone in dermatology include: • Dermatitis herpetiformis • Bullous pemphigoid • Linear immunoglobulin A dermatoses • Chronic bullous disease of childhood • Epidermolysis bullosa acquisita • Pyoderma gangrenosum • Perifolliculitis capitis abscedens et suffodiens • Subcorneal pustular dermatosis • Infantile acropustulosis • Pustular psoriasis