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].