A 53-year old white male was referred to University Hospital Limerick with a macular rash on extensor aspects of upper limb and torso, bilateral loin pain, arthralgia, fatigue, active urinary sediment and acute kidney injury in August 2015. The current presentation was preceded by two previous episodes of illness in which he had reported similar symptoms along with haemoptysis in April and July 2014. Past medical history revealed the presence of a peripapilary melanoma of the left eye treated with radiotherapy in 2010 and a basal cell carcinoma of the mid-back excised in 2000. The patient denied tobacco use and drank occasionally and denied any family history off kidney disease. He worked on a farm and was married with two children. On presentation his blood pressure was 124/70 mmHg, weight 91 kg, and there was evidence of macular rash on his back but no lower limb oedema. Urine evaluation demonstrated activity with 3+ protein and 3+ blood, and his serum creatinine was elevated at 128 mumol/L compared to a baseline of 116 mumol/L recorded in April 2014. Serology was positive for P-ANCA with a titre of 160 and he had an anti-MPO titre of over 200 units/mL; apart from this ANA was positive with a titre of 1600 with negative Anti-dsDNA, Anti-Sm, Anti-Sm/RNP and Anti-SSB/RO/LA; Serology for HIV 1 + 2 Ag/Ab and Hepatitis BsAg & Hepatitis C antibody were negative; complement levels were within normal range C3 of 0.82 g/L and C4 of 0.24 g/L. ESR was 30 mm/h and Hs-CRP was 48 mg/L; rest of his routine bloods were unremarkable (White cell count 5.8 x 109/L, haemoglobin 13.5 g/dL, neutrophils 4.00 x 109/L, platelet 210 x 109/L, sodium 141 mmol/L, potassium 4.2 mmol/L, total protein 69 g/L, albumin 39 g/L, serum calcium 2.31 mmol/L, serum phosphate 1.09 mmol/L, bilirubin 7.3 micromol/L, alkaline phosphatase 81 IU/L, gamma-glutamyl transferase 25 IU/L, alanine-aminotransferase 39 IU/L, prothrombin time 12.0 s, activated partial thromboplastin time 32.0 s). Chest X-ray was normal. A recent ultrasound of his kidneys demonstrated normal size and shape with normal cortex. A native kidney biopsy revealed evidence of moderate arteriosclerosis with 30-35% fibrosis, areas of thrombotic microangiopathy but without evidence of fibrinoid necrosis or epithelial crescents. Immunofluorescence was negative and electron microscopy revealed thin glomerular basement membranes with mean measurements less than 250 nM and many measurements less than 200 nM, consistent with thin basement membrane disease (TBMD).
Based on the presence of an AKI with active urine sediment, associated skin rash, and positive serology with high titres of P-ANCA and anti-MPO along with an antecedent history of haemoptysis, we diagnosed an ANCA-associated vasculitis likely microscopic polyangiitis (MPA) based on the European Medicines Agency Algorithm, although the kidney biopsy sample failed to demonstrate classical features of renal vasculitis. Treatment was initiated with corticosteroids and intravenous rituximab infusions (at day 0 and day 18) with prophylaxis for pneumocystis (co-trimoxazole), osteoporosis (oral Vitamin D3 and bisphosphonates), and gastritis (proton pump inhibitor). Four weeks later his urine sediment normalised with no detectable blood or protein; his CRP fell to < 5 mg/L and his ANCA titres fell to 40 but his anti-MPO level remained remarkably high 198 IU/mL. Two months later, he developed severe depression attributed to steroids requiring taper and the initiation of anti-psychotic therapy.
Six months following initial presentation, his vasculitis remained clinically quiescent and the patient was commenced on azathioprine (AZA) as a steroid sparing agent for maintenance immunosuppression. Two weeks after AZA commencement, the patient presented to the emergency department with acute painful disseminated morbilliform rash along with fever and myalgia. On examination temp was 39.7  C and a widespread indurated erythematous papular rash was noted (Fig. 1a, b). An extensive viral and immunologic work up was negative including virology for herpes zoster, and simplex. Considering his history of immunosuppression he was empirically started on acyclovir. Full blood count revealed neutrophilic leucocytosis with neutrophil count of 12.2 x 109/L, Hs-CRP 259 and ESR 59, and a stable serum creatinine concentration of 115 mumol/L. A full septic work up was negative including negative serology for HIV, hepatitis A, B, C, and CMV. A skin biopsy was diagnostic of Sweet's syndrome, in which the affected lesions revealed extensive neutrophilic infiltrate in the dermis but without evidence of leukocytoclastic vasculitis, herpes, zoster, or erythema multiform. Azathioprine was stopped and the patient was treated with oral prednisolone (30 mg once daily followed by a steroid taper) and colchicine (500 mcg twice daily). Within 4 weeks, the rash had completely resolved (Fig. 1c, d) and his inflammatory markers normalised. As the onset of symptoms were temporally related to initiation of AZA, a diagnosis of drug-induced Sweet syndrome. His steroid dose was tapered gradually to zero and treatment with colchicine was continued. As of August 2017, his vasculitis remains quiescent and there has been no recurrence of Sweet syndrome, however his ANCA titres remain elevated with anti-MPO levels 170 RU/mL.