An Unusual Type of Kidney Stone.

A very rare case of acetylsulfapyridine nephrolithiasis is presented in a 54-year-old female patient who had been prescribed sulfasalazine (6 x 500 mg/day) because of psoriatic arthritis for the last 9 years. The patient's renal function was only slightly impaired. Reflectance infrared spectroscopy and gas chromatography-mass spectrometry allowed the identification of the chemical nature of the stone. As acetylsulfapyridine is a metabolite of sulfasalazine, administration of the latter drug was the cause of the nephrolithiasis.

Immunosuppressive therapy for ocular mucous membrane pemphigoid strategies and outcomes.

PURPOSE: To evaluate the effectiveness and toxicity of a stepladder immunosuppression strategy, including the use of mycophenolate mofetil and combination therapy, in the treatment of ocular mucous membrane pemphigoid. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: Two hundred twenty-three eyes of 115 patients. METHODS: Patients with a diagnosis of ocular mucous membrane pemphigoid commencing immunosuppression between January 1994 and July 2005 were identified. A treatment episode was defined by the use of a particular therapy or combination of therapies. MAIN OUTCOME MEASURES: For each treatment episode, success of immunosuppressive therapy in controlling ocular inflammation was graded as a success (S), qualified success (QS), or failure (F). Initial and final visual acuities (VAs), stage of cicatrization (Foster, Mondino), grade of conjunctival inflammation, and side effects were recorded. RESULTS: In 70% (80/115) of patients, inflammation was controlled by the end of the study. At least 6 months remission off treatment occurred in 16 patients (14%). Of the 388 treatment episodes, 50% were classified as S; 27%, QS; and 23%, F. The most successful therapies were based on cyclophosphamide (S, 69%; QS, 21%; F, 10%), followed by mycophenolate (S, 59%; QS, 22%; F, 19%), azathioprine (S, 47%; QS, 24%; F, 29%), dapsone (S, 47%; QS, 30%; F, 23%), and sulfapyridine (S, 38%; QS, 27%; F, 35%). Combination sulfa-steroid-myelosuppressive agent therapy increased the response from 73% with single-agent therapy to 87%. Side effects were the reason for 29% of changes in therapy. These were most prominent with azathioprine (40%) and least with mycophenolate (15%). Initial best-corrected VA (BCVA) was 6/60 or less in 17% (37/223) of eyes, pemphigoid being the cause in 13% (29/223). Final BCVA was 6/60 or less in 34% (76/223) of eyes, pemphigoid being the cause in 26% (57/223). By the end of the study, Mondino stage cicatrization had progressed in 41% (92/223) of eyes and 53% (61/115) of patients. CONCLUSIONS: Mycophenolate mofetil seems to be an effective and well-tolerated immunosuppressant for moderately active ocular mucous membrane pemphigoid. Combination sulfa-steroid-myelosuppressive agent therapy in a stepladder regimen is a useful strategy to improve disease control. Cicatrization and VA may still progress and worsen despite adequate control of inflammation.

N-acetyltransferase 2 genotype-related sulfapyridine acetylation and its adverse events.

Sulfapyridine (SP), one of the metabolites of sulfasalazine (SASP), is further metabolized into N-acetylsulfapyridine (AcSP) by polymorphic N-acetyltransferase 2 (NAT2). NAT2 activity has been diagnosed by phenotyping, that is, evaluating plasma concentrations or urinary excretions of tentatively administered test drugs for dose individualization and avoidance of serious adverse events. Herein, we investigated the relationship between NAT2 genotypes and the pharmacokinetics of SP in healthy Japanese subjects, as well as the adverse events of SASP in patients with inflammatory bowel disease (IBD). Eight healthy subjects and 13 IBD patients were classified into three groups by NAT2 genotyping; the homozygote for the wild-type allele (Rapid Types), the compound heterozygote for the wild-type and mutant alleles (Intermediate Types), and the homozygote for mutant alleles (Slow Types). A single oral dose of 40 mg/kg SASP was administered to each healthy subject, and plasma and urine samples were taken until 51 and 72 h after administration, respectively. Both the SP and AcSP concentrations in each sample were determined by the HPLC method. The NAT2 genotypes were well-correlated with the plasma concentrations or urinary excretions of SP and AcSP in 8 healthy subjects, except for one Slow Type. In patients with IBD, skin rash was seen in 3 of 6 Rapid Types and 1 of 6 Intermediate Types, consistent with the concept that hypersensitive reactions are independent of serum SP concentrations. In contrast, SASP dosing-related acute pancreatitis was found in the Slow Type patient. In this case, the NAT2 activity was diagnosed by genotyping in advance, and the medical staff could pay scrupulous attention, resulting in no serious subjective symptoms such as abdominal pain, anorexia or fever. Further investigations on the relationship between the NAT2 genotype and adverse events are required, although genotyping appeared to be a promising method to avoid such serious adverse events.

Dapsone and sulfapyridine.

Dapsone and sulfapyridine are structurally related compounds with anti-microbial and anti-inflammatory effects. Dapsone remains the most important drug for leprosy and is useful in the prophylaxis of Pneumocystis pneumonia in patients with HIV disease. The medical treatment of choice for dermatitis herpetiformis is dapsone; and sulfapyridine also can be used for those patients who are intolerant of dapsone. Other neutrophilic disorders also may respond to these drugs. Toxic side effects of both dapsone and sulfapyridine are mediated through the hydroxylamine metabolite. These include hemolysis, methemoglobinemia, and agranulocytosis. Careful monitoring for possible adverse reactions includes frequently performing complete blood counts and regular blood chemistry profile determinations.

Sulphapyridine--a new agent for the treatment of ocular cicatricial pemphigoid.

AIMS: Ocular cicatricial pemphigoid (OCP) is a severe, potentially sight threatening systemic disease that sometimes requires systemic immunosuppression. This study assessed the clinical outcome of patients with OCP treated with sulphapyridine, a sulphonamide with an anti-inflammatory and immunosuppressive action but few side effects. METHODS: A prospective, single armed, unmasked clinical trial was undertaken at Moorfields Eye Hospital. Twenty consecutive patients with moderate or marked conjunctival inflammation due to OCP were treated with oral sulphapyridine 500 mg twice daily. The degree of ocular inflammation was assessed as nil, mild, moderate, marked, or severe. Success was defined as resolution to mild or less. Ocular limbitis, systemic features of the disease, and side effects of the drug were also monitored. RESULTS: Follow up was a mean of 12.3 (SD 4.0) months and ranged from 7 to 17 months. A successful reduction in inflammation was recorded in 22/39 eyes (56%) and 10/20 patients (50%). This improvement occurred within 1 month in 64% and in all by 2 months. Three patients developed allergy. Other side effects included nausea (n = 3), headache (n = 1), urinary hesitancy (n = 1), and mild lymphocytopenia (n = 1). These were dose dependent. Progression of cicatrisation was observed in 1/22 eyes. Success was less likely if there were systemic features of OCP or ocular limbitis. CONCLUSIONS: Sulphapyridine was clinically effective in 50% of patients with moderate marked inflammation and had few side effects. It is a good alternative to dapsone.

Clinical tolerance to three 5-aminosalicylic acid releasing preparations in patients with inflammatory bowel disease intolerant or allergic to sulphasalazine.

The clinical tolerance to three 5-aminosalicylic acid (5-ASA) releasing preparations (mesalazine, olsalazine and balsalazide) was assessed in a consecutive series of 43 patients with inflammatory bowel disease who were intolerant to sulphasalazine. The relative contributions to the side-effects of sulphasalazine made by its two components, 5-ASA and sulphapyridine, were also assessed in these patients. Thirty-nine (91%) patients were able to tolerate at least one of the three 5-ASA preparations. Only four (9%) patients were intolerant to all preparations, having adverse reactions previously experienced with sulphasalazine and presumably related to 5-ASA rather than sulphapyridine. The clinical tolerance to mesalazine (63%), olsalazine (70%) and balsalazide (70%) was similar, and tolerance to one drug only was found in nine (18%) patients. The commonest adverse reactions associated with 5-ASA preparations were gastrointestinal. Diarrhoea was a problem in five patients during treatment with olsalazine and three each while on mesalazine and balsalazide. Allergic reactions from 5-ASA preparations were uncommon; of ten patients with rash following sulphasalazine only one developed a rash with mesalazine. The results of this study indicate that the vast majority of patients with inflammatory bowel disease can be managed with at least one of these four 5-ASA containing preparations and that the side-effects of sulphasalazine are multifactorial in aetiology, some being due to the parent molecule, and some to one of its two metabolites, 5-ASA and sulphapyridine.

Adverse effects of the salazopyrine metabolite sulphapyridine on female fertility in the rat.

Salazopyrine, a common therapy for inflammatory bowel disease, is known to have a reversible antifertility effect in men and male rats via its metabolite, sulphapyridine. To determine if there is an adverse effect in females, 20 mature Sprague-Dawley rats were assigned to a treatment (400 mg/kg sulphapyridine daily), or a control group. After three estrous cycles of treatment, the rats were bred to males of proven fertility. When killed at 10 days gestation, there was a significant reduction in the proportion of fertilized oocytes between control (112/174) and treatment (81/212) groups (chi-square = 26.16, d.f. = 1, P less than .00001). These findings suggest an adverse effect of sulphapyridine on female fertility.

[Hypersensitivity pneumonia caused by sulfonamides]. / Hypersensitivitätspneumonie durch Sulfonamide.

A 59-year-old man with Duhring's disease (herpetiform dermatitis) developed undulating fever and pulmonary infiltrates soon after sulfapyridine treatment was started. When the drug was discontinued, a positive provocation test unequivocally established the diagnosis of hypersensitivity pneumonia. There was also a cross-reaction with sulfonyldianiline (dapsone). This case illustrates the need of considering a hypersensitivity reaction as the cause of fever and (or) pulmonary infiltration during sulphonamide administration.

Adverse effects with oral 5-aminosalicyclic acid.

Two patients with ulcerative colitis and a past history of allergic reactions to sulfasalazine had similar reactions when treated with 5-aminosalicylic acid. This suggests that, at least in some patients, the adverse effects of sulfasalazine are due to 5-aminosalicylic acid rather than sulfapyridine. Desensitization to sulfasalazine was successfully carried out in one patient but was not attempted in a second.

Clinical experience of the tolerance of mesalazine and olsalazine in patients intolerant of sulphasalazine.

We assessed the tolerance and safety of two new preparations designed to release 5-aminosalicylic acid in the colon in patients with ulcerative colitis who were intolerant of sulphasalazine. Twenty-eight of 37 patients (76%) given mesalazine and 18 of 21 patients (86%) given olsalazine tolerated the new preparations with no adverse effects. No haematologic or biochemical abnormalities were detected. Adverse reactions to the new preparations were usually but not always similar to those they had previously encountered with sulphasalazine, but a few patients experienced rash and diarrhoea. In some patients intolerant of one of the new preparations, their tolerance of the other was assessed. Three patients intolerant of mesalazine tolerated olsalazine. Similarly, three other patients intolerant of olsalazine tolerated mesalazine. We conclude that not all adverse effects of sulphasalazine are due to the sulphapyridine part of the molecule. Some are due to the released 5-aminosalicylic acid and some to the parent compound. Both drugs are likely to prove useful in the management of patients intolerant of sulphasalazine.

A study to determine the active moiety of sulphasalazine in rheumatoid arthritis.

Thirty patients with active rheumatoid arthritis (RA) participated in an open study of 6 months' treatment with either 5-aminosalicylic acid (5-ASA) or sulphapyridine (SP), the two moieties of sulphasalazine (SASP). Patients were assessed at regular intervals using clinical and biochemical tests designed to detect specific antirheumatic activity. Patients taking SP showed significant improvement in disease activity, but those taking 5-ASA did not improve, despite the fact that high serum concentrations of 5-ASA and acetyl 5-ASA were achieved. These results suggest that SP is the active moiety of SASP. Its possible mode of action is discussed. Nausea was a frequent problem in patients taking SP. Unless this can be overcome, SP is unlikely to offer any therapeutic advantages over SASP in the treatment of RA.

Which component of sulphasalazine is active in rheumatoid arthritis?

Sulphasalazine is known to be effective as a second line agent in the treatment of rheumatoid arthritis. The two chemical constituents of sulphasalazine (sulphapyridine and 5-aminosalicylic acid) were assessed separately in the treatment of rheumatoid arthritis. Over 24 weeks sulphapyridine showed a pronounced second line effect comparable with sulphasalazine and with a similar toxicity profile, whereas 5-aminosalicylic acid showed only a weak first line effect. Thus sulphapyridine appears to be the active moiety responsible for the second line effect of sulphasalazine in rheumatoid arthritis. The efficacy of the antibacterial component of sulphasalazine yet again permits speculation about the role of a bacterial pathogen in the aetiopathogenesis of rheumatoid disease.