IntroductionSevere cutaneous adverse reactions (SCARs) are delayed heterogeneous hypersensitivity reactions triggered by drugs in the majority of cases. They present as emergencies on acute services. Manifestations of SCAR’s can include blistering, exfoliation, pustulation and mucosal involvement which usually alert the physician to scrutinize the drug history. The rash of DRESS is highly variable and can be non-specific in morphology raising a wider differential diagnostically. The prodromal phase of DRESS with fever, malaise and arthralgia may also raise alternative diagnoses including lymphoma[1]. The drug latency period for DRESS from drug exposure to disease onset has a median (range latency) of 24.5 (1-160 days) and can frequently be overlooked as most drug induced rashes emerge within 1-3 weeks of initiation and drug history recordings tend to focus on new or recent drug initiation[2].Case History and ExaminationA forty seven year old Caucasian female presented with skin rash, fever, and flu like symptoms She had a fever 38.9 and felt generally lethargic. She had generalised myalgia and arthralgia. Although non specific in morphology, her rash was very extensive and maculopapular with background confluent erythema affecting entire trunk, upper limbs and thighs (75% body surface area). There was no blistering or mucosal involvement. She had facial swelling with palpable bilateral parotid swelling and extensive palpable cervical lymphadenopathy (1cm) and inguinal lymphadenopathy (1.5 cm).Differential Diagnosis Investigation and TreatmentHaematological profile showed a normal haemoglobin and a lymphopaenia 0.5 (1-3) and atypical lymphocytes were identified. She had prominent eosinophilia 1.67 (0-0.5). CRP was elevated at 94 (0-5) and ESR was elevated at 116 (0-12). LDH was elevated at 252 (135-214). Hepatic profile showed significant abnormalities with baseline ALP 155 (35-104), ALT 81 (0-40), GGT 138 (6-42). Albumin levels were reduced 31 (39-51). Renal function showed elevated creatinine levels 122 (49-90) with normal urea, reduced sodium 126 (136-145) and reduced eGFR 45 (60-160). Hepatic virology screening was negative as were PCR screening tests for EBV, CMV, Herpes, Mumps, Rubella and HIV. Full autoimmune screening was negative.Abdominal ultrasound confirmed prominent hepatosplenomegaly (14 cm spleen) (Figure 1) with prominent para-aortic and porta hepatic lymph nodes. Features were suggestive of lymphoma and she was scheduled for bone marrow and lymph node biopsy. CXR showed a lower lobe consolidation with pleural effusion and atelectasis of the right horizontal fissure. Cardiac echo identified a pericardial effusion with normal ejection fraction (Figure 2).The differential diagnosis initially considered was Lymphoma or severe viral exanthem.Outcome and follow-upOn dermatologist advice, an extended review of her drug history over the previous 4 months was undertaken which revealed exposure to diclofenac 100mg twice weekly, and ibuprofen 600mg 5 days a week intermittently over the previous 10 weeks for back pain. A presumptive alternative diagnosis of DRESS with multi organ involvement was proposed. She was commenced on systemic steroids 0.5mg/kg orally and an intensive topical therapy regime which included super potent topical steroids and emollients.Within 72 hours her fever resolved fully and her cervical and inguinal lymphadenopathy dramatically reduced to the extent that lymph node and bone marrow biopsy were deferred. Her skin rash improved and settled in 10 days. Her systemic symptoms gradually improved over the following weeks and months. Given the severity and extent of multiorgan involvement and given that DRESS has been reported to relapse and remit, she remained on a reducing steroid regime for 3 months. Regular monitoring during this time revealed that all abnormal blood parameters had gradually returned to normal values. Repeat CXR, cardiac echo and abdominal ultrasound were normal at 3 months and her steroids were stopped without relapse.DiscussionA clear drug trigger can be identified in approx. 80% of DRESS cases. Approximately 75% of cases are due to a small few high risk drugs incl anticonvulsants (carbamazepine, phenytoin, and lamotrigine), allopurinol, and sulphonamide containing antibiotics, minocycline and Vancomycin. There are much fewer reports implicating drugs such as NSAID’s, the likely trigger in this case and there are recent reports of DRESS are associated with tyrosine kinase inhibitors, BRAF inhibitors, MEK inhibitors and Immunotherapy [3]. With ever expanding novel drug regimes and exposures, it is predictable that clinical presentations of DRESS will continue to present.Pharmacogenetic studies have found an association between DRESS risk and several HLA haplotypes[4]. DRESS is a T –cell mediated immune response. The pathogenesis is not fully understood, but a drug specific immune response associated with explosive cytokine release and the possible reactivation of viruses from the Herpesveridiae family eg. HHV-6 most notably (16%-60% of cases) but also Ebstein- Barr virus (EBV), and cytomegalovirus (CMV) [5]are the suspected mechanisms.Only 20% of DRESS patients have more than two organs involved and the condition has a reported mortality rate of up to 10% which rises when cardiac and renal involvement and advancing age are features. 11% of DRESS patients experience long term autoimmune sequelae thyroiditis, diabetes or chronic renal failure[6]. Early withdrawal of any drug trigger and prompt intervention with systemic steroids is critically important. Immunosuppressive agents such as Cyclosporin may sometimes be additionally required. Recognition and prompt intervention is vital and ultimately will help to distinguish DRESS from diseases that it can closely mimic most notably lymphoma and will prevent diagnostic delay and unnecessary investigations.AUTHOR CONTRIBUTIONSHilary Regan – data collection, first draft and revisions, manuscript layout and designGerard O Sullivan - procurement, interpretation and preparation of radiological imagesPauline Marren – supervision, patient consent, editing and final draftREFERENCES1.Mangana J, Guenova E, Kerl K, Urosevic-Maiwald M, Amann V et al. Angioblastic T-cell lymphoma mimicking drug reaction with eosinophilia and Systemic symptoms (DRESS syndrome) Case Rep Dermatol 2017;9:74-792.Kridin K, Bruggen MC, Walsh S,Bensaid B,Ranki A et al. Management and treatment outcome of DRESS patients in Europe: An international multicentre retrospective study of 141 cases.J Eur Acad Dermatol Venereol 2023;37:753-7623.Kardaun SH,Sekula P,Valeyrie-Allanore L, Liss Y,Chu CY et al. Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from prospective RegiScar study. Br J Dermatol 2013;169:1071-1080.4.Tempark T,Satapornpong P,Rerknimitr P, Nakkam N, Satsit N et al. Dapsone induced severe cutaneous drug reactions are strongly linked with allele HLA-B*13;01 in Thai population. Pharmacogenet Genomics; 2017:12: 429-4375. Miyagawa F, Asada H. Current perspective regarding the Immunopathogenesis of drug-induced hypersensitivity syndrome / DRESS. Int J Mol Sci;2021:22:21476.Long term sequelae of drug reaction with eosinophilia and systemic symptoms –a retrospective cohort study from Taiwan. J Am Acad Dermatol:2013:68:459-465