Leukemoid Reaction in Sulfasalazine-Induced Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome: Recognition and Management of a Rare Complication

Dear Editor, Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a severe cutaneous drug reaction (SCAR) characterised by rash, fever, lymphadenopathy, multi-organ involvement and eosinophilia. Though an uncommon occurrence, there are a few reports of LRs in DRESS with drugs such as dapsone, phenobarbital, sulfasalazine and minocycline [Table 1].[1-4] We describe here a case of sulfasalazine-induced DRESS syndrome complicated by LR.Table 1: A brief literature review of leukemoid reaction in DRESS reported till dateA 46-year-old woman presented with fever, rash and facial swelling three weeks after sulfasalazine (500 mg twice daily) was prescribed for inflammatory arthritis. On examination, erythematous, blanchable maculopapular rash with scaling was seen involving trunk, bilateral upper and lower limbs [Figure 1]. Her total leukocyte count on Day 1 was 4.7 × 109/L and liver enzymes were also borderline elevated (ALT = 53, AST = 46). She was clinically diagnosed as DRESS [RegiSCAR score = 4]; sulfasalazine was identified as the probable incriminating drug [Naranjo score = 5] and discontinued on admission. She was started on oral prednisolone (40 mg/day) with significant improvement in the rash in the next three days. However, her leukocyte count steadily rose over the next week to reach a peak of 114.6 × 109/L on Day 6 [Figure 2]. Her sepsis screen was negative, and an urgent haematology consult was taken. The peripheral smear showed leukocytosis (neutrophilia and eosinophilia) with shift to left (myelocyte and meta-myelocyte). The Leucocyte Alkaline Phosphatase (LAP) score is 124 (Reference range 20–124). To rule out a haematological malignancy, myeloproliferative panel (PCR for BCR-ABL-1, JAK2, CARL and MPL gene) was done however no mutation was detected. Thus, we diagnosed her as a case of DRESS with LR.Figure 1: Erythema, oedema and induration seen over the faceFigure 2: Line diagram showing the leukocyte counts and eosinophils from Day 1 to Day 8Oral corticosteroid dose was hiked (prednisolone = 60 mg/day), with improvement in erythema and leukocyte count. Our patient improved on Day 9 with a total leukocyte count of 30.9 × 109/L. On her follow-up visit two weeks later, her leukocyte count returned to normal range [ TLC = 8.4 × 109/L]. Sulfasalazine is widely used in managing conditions such as ulcerative colitis, rheumatoid arthritis and ankylosing spondylitis. However, it may occasionally lead to the development of DRESS, which is an idiosyncratic reaction characterized by the involvement of multiple organ systems, diverse clinical features (including fever, rash, lymph node enlargement and elevated eosinophil levels) and an unpredictable progression. The development of the rash corresponds to the duration of drug intake, often occurring after a latency period. A systematic literature review of 39 cases of sulfasalazine-induced drug rash reported a median onset time of DRESS at 28 days (range: 10–60 days) following administration.[5] This patient developed DRESS syndrome three weeks after initiating sulfasalazine at a dose of 500 mg twice daily. Leukemoid reaction (LR) is a transient haematological syndrome of reactive nature characterised by persistent leukocytosis of more than 50 × 109/L.[6] It can occur with many disorders such as severe infections, intoxications, malignancies and severe haemorrhage.[7] In the absence of malignancy and severe infection, we attributed the LR to the drug. Improvement with discontinuation of the incriminating drug and steroids for DRESS further supported the diagnosis. The exact mechanism behind LR in DRESS remains unclear; however, over-activation of immune system and cytokine release may be involved in the exaggerated bone marrow response.[4] DRESS can be a potentially life-threatening reaction; in a sick patient, a rising count can further alarm the physician. This case highlights that a wait-and-watch approach with continued steroids will often lead to the resolution of the LR. Recognising and conservative management of the reaction should lead to favourable patient outcomes. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.