Induction of Tolerance to Non Steroidal Anti Inflammatory Drugs Might Be an Alternative Therapeutic in the Painful Crisis of Sickle Cell Disease

Abstract

Background and Aims: In Ivoirian's school, the management of vaso-occlusive painful crisis in sickle cell disease requires non steroidal anti inflammatory drugs (NSAIDs). Although their effectiveness, these drugs may be accompanied by intolerance reactions. When these occur, no codified alternative therapeutic seems to be used to our knowledge. Authors aimed to evaluate the induction of tolerance to NSAIDs as an effective alternative therapeutic. Methods: 22 patients (15 men and 7 women aged from 12 to 39 years with mean age: 22.41 ± 7.88) suffering from vaso-occlusive painful crisis were enrolled. They were known to have a history of sickle cell disease and at least one episode of adverse reactions following the Ibuprofen or Diclofenac intake. A rapid protocol of oral challenge was used in patients to induce tolerance to NSAIDs. The first day, initial doses (8.82 mg for Ibuprofen and 2.20 mg for Diclofenac) were given and gradually increased at intervals of 1 hour over a total period of 6 hours. On the second and third days, the therapeutic dose has been orally administrated with an interval of 6 hours over a period of 12 hours. Results: Despite of some cases of failure that might be related to the severity of symptoms or possible patho-physiological mechanism, more than 80% of patients have successfully tolerated Diclofenac and Ibuprofen. Conclusion: This experience appears to be the first in our context. It might be used as a solution in the lack of alternative therapeutic in the management of vaso-occlusive painful crisis of sickle cell disease as well as in other diseases such as HIV infection where patients often develop intolerance to none alternative antibiotics.

CTH1/TH2 repolarization in induction of immune tolerance to non-steroidal anti-inflammatory drugs during the management of sickle cell disease vaso-occlusive crisis

“…12 The absence of a known alternative therapeutic that could be effective led us to set up a short threeday protocol to induce immune tolerance to NSAIDs such as Ibuprofen. 6 During the clinical follow-up, the complete disappearance of the initial signs of intolerance was noted, as shown in Table III comparatively to Table I. Despite two cases of failure that we observed through the occurrence of rhinitis and eczema at M1, the protocol noted at M6, a success with a complete disappearance of the signs during the reintroduction of NSAIDs.…”

“…8 NSAID-intolerant asthma frequently begins after the age of 30 9,10 and reactions to NSAIDs are not always immunological. 11 The symptomatology found takes on a clinical form of anaphylaxis 6 to the point that it was dangerous to continue. Indeed, the involvement of inflammation in the painful vaso-occlusive crisis justifies the use of NSAIDs in the management of sickle cell disease.…”

“…A total of 55 sera samples were collected from the 11 study patients, followed up over 6 months (Pre-induction, D1, D3, M1, M6) as previously described. 6 These samples were stored at -80°C for 8 years (2014 to 2022), were gradually thawed overnight at ambient laboratory temperature, then they were well homogenized. They were first diluted at 1:20.…”

“…The result of this short 3day protocol showed the complete disappearance of respiratory signs in 80% of patients. 6 Understanding the basic mechanisms of this tolerance induction led the authors to evaluate the profiles of cytokines involved in the immune response.…”