Anaphylaxis to polyvinylpyrrolidone in an analgesic preparation.

A 32-year-old patient developed an anaphylactic reaction minutes after oral intake of acetaminophen-containing tablets (Doregrippin)). Scratch testing of the whole preparation was positive in contrast with the negative results obtained with pure acetaminophen. Therefore, scratch tests with the remaining drug components were performed and showed polyvinylpyrrolidone (PVP) to be the aetiological agent. Furthermore, specific IgE antibodies against PVP were demonstrated using a dot blot technique, thus ruling out a pseudo-allergic reaction. This case underlines the necessity to consider not only the active ingredient, but also additives as the causative agent.

Pyoderma gangrenosum after cesarean delivery.

In this reported case of pyoderma gangrenosum after cesarean delivery, deep ulceration involved the entire lower abdomen before immunosuppressive treatment was started. Initial high doses of prednisolone followed by low doses of cyclosporine A led to complete resolution of the skin lesions. This case report illustrates the importance of early diagnosis and effective systemic immunosuppressive therapy of pyoderma gangrenosum.

[Combination of antimalarial drugs mepacrine and chloroquine in therapy refractory cutaneous lupus erythematosus]. / Kombination der Antimalariamittel Mepacrin und Chloroquin bei therapieresistentem kutanem Lupus erythematodes.

Antimalarials represent the first line in treatment of cutaneous lupus erythematosus (LE). However, some patients show no improvement on monotherapy with chloroquine or hydroxychloroquine. A 30-year-old female patient had treatment-resistant cutaneous LE exhibiting features of both LE tumidus and subacute cutaneous LE. Previously, the patient had been unsuccessfully treated with chloroquine, hydroxychloroquine, dapsone, and azathioprine, each in combination with variable doses of prednisolone. However, the LE lesions increased during these therapeutic regimens. A combination of chloroquine and mepacrine therapy led to improvement and then total clearing after 4 months of treatment.

Polymorphisms of the xenobiotic-metabolizing enzymes CYP1A1 and NAT-2 in systemic sclerosis and lupus erythematosus.

The etiology of systemic autoimmune diseases, such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is still unknown. In several cases, however, xenobiotics (i.e. drugs and occupational agents) were identified as etiologic agents and associations with certain polymorphic alleles of xenobiotic-metabolizing enzymes have been reported. Cytochrome P4501A1 (CYP1A1) and N-acetyltransferase 2 (NAT-2) are xenobiotic-metabolizing enzymes of phase 1- and phase 2-metabolism, respectively. CYP1A1 may activate drugs and other chemicals to reactive metabolites. NAT-2 is the most important enzyme in acetylation of aromatic amines, and thus may be responsible for detoxification of many of these compounds. Two polymorphisms of the human CYP1A1 gene, a point mutation in the 3' flanking region of the gene (Msp1) and a mutation in exon 7 leading to an isoleucine-valine-exchange in the heme-binding region of the enzyme, have been described and may lead to a higher basal and inducible enzyme activity. With respect to NAT-2, several alleles which combine for the two phenotypes "fast" and "slow" acetylators have been described. We analyzed the gene frequencies of the CYP1A1 polymorphisms and the phenotypes of NAT-2 in patients suffering from idiopathic SLE or SSc. CYP1A1 polymorphisms were analyzed in genomic DNA by PCR, whereas NAT-2 phenotypes were measured by the caffeine method. For CYP1A1 polymorphisms, 106 patients have been typed until now. The SLE group (n = 68) exhibited a significant increase (p < 0.05) in the mutant Val-allele (OR = 2.59) when compared to controls (n = 184). However, no significant differences in allele frequencies for MspI in the SLE group and for both CYP1A1 polymorphisms in the SSc group could be observed. Regarding the NAT-2 phenotype, patients suffering from SLE (n = 88) 75% and SSc (n = 26) 80.2%, respectively, were slow acetylators compared to 55% slow acetylators in the healthy German population (p < 0.05). The observed increased frequencies of the CYP1A1 mutant Val-allele and the slow actylator phenotype in idiopathic autoimmune disease support our concept that in slow acetylators non-acetylated xenobiotics may accumulate and are subsequently metabolized by other enzymes into reactive intermediates. Thus, enhanced formation of reactive metabolites could alter self-proteins presented to the immune system thus stimulating autoreactive T cells which induce autoimmunity.

Cutaneous adverse reaction to ciprofloxacin: demonstration of specific lymphocyte proliferation and cross-reactivity to ofloxacin in vitro.

Ciprofloxacin (CPFX) is a widely used fluoroquinolone antibiotic, inducing cutaneous adverse drug reactions in about 1 to 2% of the treated patients. Conclusive diagnosis of drug allergy, however, still remains a major problem in daily clinical practice. Here, we present 2 patients with drug allergy to CPFX. In both cases the clinical suspicion for CPFX as the causative agent was confirmed in vitro by means of the lymphocyte transformation test, whereas epicutaneous patch tests remained negative. In vivo, a small percentage of the drug is biotransformed to the three major metabolites desethylene-, sulfo- and oxociprofloxacin. Though structurally closely related to their mother compound, these metabolites failed to induce in vitro lymphocyte proliferation in both patients. On the other hand, in vitro crossreactivity to ofloxacin, another fluorinated quinolone, could be demonstrated, which to our knowledge has not previously been reported.

Lamotrigine-induced Stevens-Johnson syndrome: demonstration of specific lymphocyte reactivity in vitro.

The novel antiepileptic drug lamotrigine (LTG) is effective as an adjunctive medication in partial seizures. The main adverse effects of LTG are skin eruptions, occurring in 3-10% of the treated patients, but these are rarely severe. The risk of cutaneous side effects is increased in patients receiving sodium valproate comedication, probably by doubling the plasma half-life of LTG due to competition with hepatic glucuronidation. Conversely, the risk can be reduced by adding LTG in a lower dose. Here, we report a patient who developed Stevens-Johnson syndrome (SJS) 5 weeks after adding low-dose LTG comedication to sodium valproate. An LTG-induced pathogenesis of the SJS was considered likely by a positive lymphocyte transformation test to the drug. The patient showed maximal peripheral blood lymphocyte reactivity to 50 micrograms LTG/ml with a stimulation index of 4.7 but not to nontoxic concentrations of sodium valproate. Lymphocytes from untreated controls neither reacted to LTG nor to sodium valproate.