Discussion:
Severe cutaneous adverse reactions (SCARs) are a class of life-threatening adverse drug responses affecting the skin and the mucosal surfaces (oral, genital, ocular etc). They can cause severe damages to internal organs in more critical cases. [4]
Drug reaction with eosinophilia and systemic symptoms (DRESS) is part of SCARs and it constitutes a challenge with regard to diagnosis, management, and treatment. [4]
The pathophysiology of DRESS is not yet fully understood. It has been suggested that certain drugs may cause hypersensitivity reactions in patients with genetic or acquired mutations in the drug metabolism pathways, due to abnormal production and detoxification of their active metabolites. Allopurinol was introduced in 1963 as a uric acid-lowering drug. Its mechanism of action involves its conversion to oxypurinol after being absorbed. It is speculated that excessive oxypurinol can cause tissue damage, trigger immune response, and produce antibodies against tissue components. Others have invoked cell-mediated immunity [5] [6]. Virus reactivation, especially human herpes virus 6 (HHV-6), has been considered an important factor in the pathogenesis of DRESS syndrome [7]
Several diagnostic criteria have been utilized to standardize DRESS diagnosis. Bocquet et al. were the first to propose criteria for the diagnosis of DRESS in 1996 [8] [Table 1].In 2007 [Table 1], the Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) group added criteria to diagnose DRESS syndrome and a scoring system to provide a more precise definition. [Table 2,3] [9]. This system tends to be the most widely used and accepted tool. Another set of diagnostic criteria was proposed by a Japanese group[10] [Table 4, 5]. The use of this Japanese model is limited because it requires laboratory measurement of Ig G anti HHV6, which is not routinely available. Using the RegiSCAR scoring system, our patient’s score was 6, indicating that it was a definite case of DRESS syndrome.
Drug history was the key to diagnosis in our case as Allopurinol had been incriminated in several cases of Allopurinol-induced Dress syndrome. [11]
Diagnosis of (DRESS) is still challenging on multiple levels despite the presence of well-defined criteria. Dermatological involvement presents a notable overlap among the other SCARs, such as Stevens-Johnson syndrome (SJS), Toxic Epidermal Necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). No pathognomonic skin rash pattern for DRESS is available. [12] Systemic symptoms and negative Nikolsky’s sign are two clinical indicators differenciating DRESS from other maculopapular drug eruptions. Skin biopsy is the gold standard for diagnosis. Subepidermal bullae are present in SJS/TEN; however, eosinophilic infiltrate is present in DRESS.
The timing of cutaneous manifestations is also challenging in terms of diagnosis because DRESS and SJS/TEN overlap. Indeed, SJS usually occurs within 1 to 3 weeks while DRESS occurs within 6 weeks of the drug administration [13] as observed in our patient.
Other differential diagnoses for DRESS syndrome include acute infections (viral exanthemas, streptococcal, and staphylococcal shock syndrome), autoimmune diseases (hypereosinophilic syndrome, and Kawasaki disease), and neoplastic diseases (lymphomas) [14].
Involvement of the oral mucosa and the vermillion border in DRESS syndrome is frequent. The usually encountered manifestations are nonspecific, including cheilitis [15], erosions [16], crusting lips [17], and edema [3] as observed in the reported case.
There are no specific treatment guidelines for DRESS syndrome management. The only definitive treatment is to identify and eliminate the culprit drug. [18] In our case, Allopurinol cessation led to healing in 15 days.
For patients with internal organ involvement, systemic corticosteroids are the main treatment. It is recommended to use medium to high doses of systemic corticosteroids until clinical improvement and laboratory normalization are obtained [ 19].