¹Entesar N Etrug, ²Ahmed S Zayat

¹University hospital Sharjah, ²University of Sharjah

Background(s): 41 years old Emirati Arabic female was admitted with eight weeks history of severe cough and dyspnoea which failed to respond to oral and IV broad spectrum antibiotics after initially diagnosed as chest infection.  She developed red painful eyes, fatigue, painful wrists and ankles and loss of sensation in right ulnar nerve distribution.  Her CRP was very high (647 mg/L), anaemia (Hb 8.1 g/dL, MCV 58 fL), thrombocytosis (648 cellsx109 /L),  She has a family history of psoriasis (brother), rheumatoid arthritis (sister), and celiac disease (brother).  Eyes examination revealed features suggestive of vasculitis scleritis.  HRCT showed multiple bilateral patchy alveolo-interstitial infiltrates in both lungs involving both upper lobes, lower lobes and right middle lobes, some showing tree in bud appearances associated with ground glass attenuation and associated septal thickening (Figures A-B).  Nerve conduction confirmed features of right ulnar nerve mononeuritis multiplex.

Method(s): Sonographically, she had moderate synovitis in right second metacarpophalangeal joint with erosion, tenosynovitis of 1st and 6th extensor compartments in the wrist and right Achilles enthesitis (Figures D-E).  Blood test revealed positive c-ANCA PR3 ( 1:1000) , Rheumatoid factor (RF) (92 mg/L), negative CCP, positive ANA (granular)(1:320), positive anti dsDNA antibodies (1:100).  Normal C3 (1.76 g/L) and mildly raised c4 (0.49 g/L), normal ferritin (66.0 ug/L), mild raised urine protein (206 mg/ L (60-140)) with normal creatinine and liver function.  Patient has no tissue amenable to biopsy.  Based on clinical and serological finding patient was diagnosed as ANCA positive vasculitis with evidence of pulmonary, ophthalmic and nerve vasculitis and arthritis.  Patient had erosive polyarthritis  with positive RF suggestive of rheumatoid arthritis and significant enthesitis with strong family history of psoriasis.  Patient was ds-DNA positive but no features of lupus.

Result(s): Patient was given prednisolone 40mg daily with gradual tapering and had two infusions of Rituximab 1000mg IV two weeks apart.  After which she has improved significantly within 4 weeks with complete resolution of chest symptoms, eyes signs and symptoms and dropping of CRP <4 and urine protein to <60 mg/L  and haemoglobin improved to 11.7 g/dl and platelets to 445 cellsx109 /L with resolution of chest radiography findings (Figures C & E).  She continued to stay to be c-ANCA PR3 and dsDNA positive after Rituximab therapy.   Ulnar mononeuritis multiplex symptoms completely resolved after 4 months.  Patient was initiated on azathioprine 100 mg (2mg/ kg) which caused mild neutropenia and subsequently dose was dropped to 50mg daily.  Patient however continued to suffer from right Achilles tendon enthesitis pain and ultrasound showed left Achilles tendon severe enthesitis with erosions, calcification, enthesophyte, abnormal tendon echogenicity and thickness and severe power Doppler signal and retrocalcaneal bursitis (Figure d).  In the right side there was moderate enthesophytes and features of enthesitis and mild bilateral plantar fasciitis.  Patient started to have 13 tender joints and 4 swollen joints 8 months after last dose of Rituximab with no flare of pulmonary, neurological, renal, ophthalmic vasculitis features.  Patient was switched to Upadacitinib and improved significantly and achieved 2 swollen joints within 3 months and no swollen or tender joints after 6 months with resolution of all enthesitis.  She continued maintenance of Upadacitinib 15mg and azathioprine 50mg combination.  c-ANCA became negative after Upadacitinib treatment.  Patient reported weight gain of  5 kg since starting Updacitinib.

Conclusion(s): Rare cases of overlap of ANCA positive vasculitis and rheumatoid has been previously reported, however the combination of that with polyenthesitis and ds DNA-positivity was unique.  The response of the vasculitis and arthritis components but no the entheistis to Rituximab was probably due to different autoimmune drive independent off B cells, given the strong psoriasis family history and might indicate poliautoimmunity  with  autoimmunity activity at different pathways simultaneously.  The effectiveness of JAK inhibitor (Upadacitinib) as a maintenance therapy in this case was of special interest and might guide treatment in future patients with similar overlap syndrome