Wu K, Reynolds NJ.. 2012 Jan;166(1):7-11. PMID: 22212057
Carbamazepine-induced severe adverse reactions are a cause for concern due to their associated morbidity and mortality. Of course, the possibility of determining by means of a test the patient’s risk of developing such a complication would have important implications in our everyday clinical practice. Dr. Wu and Dr. Reynolds comment on two very recent papers published in the New England Journal of Medicine, focusing on the relationships between specific HLA alleles and adverse drug reactions with carbamazepine.
Undoubtedly, although more studies are required to develop personalized medicine, this is a very interesting field of research.
Drug-induced subacute cutaneous lupus erythematosus (DI-SCLE) is a challenging disorder. In a recent issue of the British Journal of Dermatology, Dr. G. Lowe and co-workers have published a very interesting comprehensive systematic review of the cases reported. The authors deal in depth with its pathogenic mechanisms, management and prognosis:
Lowe G, Henderson CL, Grau RH, Hansen CB, Sontheimer RD. Br J Dermatol. 2011 Mar;164(3):465-472. PMID: 21039412
Dr. Lowe and collaborators identified 117 cases of DI-SCLE, reported in English language publications, and conclude that:
- DI-SCLE is clinically, histopathologically and immunologically indistinguishable from idiopathic subacute cutaneous lupus erythematosus.
- Incubation periods are variable and depend on the drug class. It is important to stress that long incubation periods, lasting years, have been reported. With respect to resolution, once the offending drug is stopped the majority of cases resolved within weeks, with or without specific treatment.
- The majority of patients positive for Ro/SS-A or La/SS-B remain positive after DI-SCLE has resolved.
- Histone antibodies testing was performed in 57 of the 117 cases, and one-third of these patients were positive for histone antibodies.
- The majority of patients suffering from DI-SCLE have not been reported to progress to idiopathic systemic lupus erythematosus or Sjögren’s syndrome. The authors underline that follow-up time may not be long enough to confirm these data.
- The aetiopathogenesis of DI-SCLE is still confuse. Taking into account that many different types of drugs can trigger it, it is possible that more than one mechanism precipitates the disorder. However, it is generally considered that these drugs induce a photosensitivity state which, in individuals with an immunogenetical predisposition, would cause the disease via an isomorphic response.
- Patients are generally treated with steroids, topic or systemic, hydroxychloroquine and topical tacrolimus.
- As currently there are no tests to identify the specific drug that elicits DI-SCLE, in patients receiving multiple treatments the authors recommend to discontinue, if possible, all drugs that could be responsible for the disorder.
As limitations, Dr. Lowe and collaborators remember the readers that the data analysis is retrospective. In addition, the authors consider the possibility of under-identification of cases not included in English speaking papers. Under-reporting of certain drug classes is also possible.
The authors underline the importance of recognizing this entity as most cases resolve if the causative agent is withdrawn, saving the patient from unnecessary procedures and treatments.
Drug eruptions are a frequent complication seen in approximately 2% to 3 % of hospitalized patients. Some of these eruptions have a characteristic clinical picture such as erythema multiforme, fixed drug eruption, vasculitis, or acute generalized exanthematic pustulosis. However, most patients present with less specific rashes such as morbilliform drug eruptions, or urticaria that can account for up to 95% of cutaneous drug reactions. The diagnosis of drug eruptions is based on clinical history, particularly when the rash is temporally related to the introduction of a new drug, in the last days or weeks. Most drugs that the patient had been taking for years can usually be excluded as triggering agents. In addition, the clinical features of the rash, and, in some cases, the histopathologic examination of a cutaneous biopsy can help in diagnosis.
Although some drug eruptions have histologic patterns that make them easily diagnosed, in most patients histology is ‘‘non-specific’’ or ‘‘non-diagnostic’’. In a study published in the December issue of the Journal of the American Academy of Dermatology the authors have made a revision of the of cutaneous drug eruptions diagnosed over a 5-year period. A total of 104 cases were included in the study. In 83% of the cases, the suspected drug or drugs could be narrowed to 3 or fewer. The two most frequent classes of drug associated with the appearance of a rash were antibiotics (45%) and antiepileptics (15%). 94% of the rashes were morbiliform. Most of the biopsies (80%) showed superficial dermal inflammatory infiltrates in a combined perivascular and interstitial pattern. There were interface changes in 53% of the biopsies. The inflammatory infiltrates was composed of lymphocytes only in 32% of the cases, lymphocytes and eosinophils in 29% of the cases, lymphocytes and neutrophils in 10% of the cases, and lymphocytes, neutrophils and eosinophils in 21% of the cases. Therefore, 50% of the cases contained eosinophils in the infiltrate. In summary, the finding of superficial infiltrates with or without interface changes, with the presence of eosinophils is the most frequent histologic pattern observed in morbilliform drug eruptions. (more…)