3. A Case of Post-Partum Auto-inflammatory Syndrome

A case of a 25 year old lady, whose condition drastically deterioratedfollowingaCaesareansection, isdescribed. Case description: Severe acute illness A 25 year old lady, Ms A, was admitted on 6th May 2017, eleven days post-Caesarean section. She presented with a high fever, non-specific widespread rash, breathlessness and signs of a systemic illness. Investigations showed normocytic anaemia (haemoglobin: 107 g/L (reference range: 120-150 g/L); mean corpuscular volume: 88 fL (reference range: 83-101 fL)), normal platelet and neutrophil counts and low lymphocyte count (0.74 x 10^9/L (reference range: 1-3 x 10^9/L)). C-reactive protein (CRP) was 29 mg/L (reference range: 0-10 mg/L). Chest radiograph and computed tomography (CT) scan abdomen and pelvis were normal. Broad-spectrum antibiotics (intravenous vancomycin, metronidazole and gentamicin), were started forsuspectedsepsis inviewofpenicillinallergy.Repeatchest radiograph on day two of admission showed evidence of bilateral increased lower zone density. Clarithromycin and meropenem were added on day two anddaythreeoftheadmissionrespectively, forsuspectedbi-basalpneumonia.Herconditioncontinuedtodeteriorate.Whitecellcount increased to 18.6 x 10^9/L (reference range: 4-10 x 10^9/L) on day three of admission and she developed thrombocytopenia; platelet count: 14 x 10^9/L on day four of admission (reference range: 150-410 x 10^9/L). There was also evidence of a marked acute phase response; ferritin>2000 mg/L on day six of admission (reference range: 23-300 mg/L). Due to hypoxia and high risk forpulmonary embolus (pregnancy, Caesareansection,obesity and immobility), CT pulmonary angiogram was undertaken on day two of admission. This demonstrated small pleural effusions and bi-basal consolidation but no embolus. On day eight, she received a 500mg dose of intravenous methylprednisolone and commenced prednisolone 40mg daily. Her acute illness settled. Platelet count returned to normal by day nine of the admission. Ferritin levels had fallen to 893mg/L after two days. Ms A had been taking heparin throughout her pregnancy, which was stopped when she became thrombocytopenic post-partum. On day nine, she developed worsening shortness of breath with oxygen desaturation, and type 1 respiratory failure. A ventilation/perfusion scan on day ten of the admission was indeterminate. A second CT pulmonary angiogram confirmed several right lower lobe segmental and subsegmental pulmonaryemboli.Shedeclinedwarfarinbutagreedtorivaroxabantreatment.Shewasdischargedafteraneighteen-day inpatientstay, including two high dependency unit admissions. A follow-up review ten days later showed a complete resolution of symptoms. Ferritin was normal at 129 mg/L. Hydroxychloroquine was started at this point. Her prednisolone dose was tapered from 20mg daily at the time of discharge by 5 mg every 2weeks.Background MsA hadoriginally presented to the rheumatology outpatient clinic thirteen months prior with hand and foot joint pain and swelling. Her symptoms were associated with reduced grip strength and manual dexterity. Therewas apast medical history of longstanding, controlledepilepsy.Therewasnohistoryofphotosensitivity rash,Raynaud’s phenomenon, pleurisy, sicca symptoms or thrombosis. Blood tests revealed a raised erythrocyte sedimentation rate (ESR) of 40 mm/hr (reference range: 0-12 mm/hr), positive anti-nuclear antibodies (6.1), extractable nuclear antigen antibodies (23) and anti-Ro antibodies (>600). Anti-double stranded DNA antibodies were negative (2.8 IU/ml). At that time, symptomatic treatment of polyarthralgia, in the form of naproxen and lansoprazole, was instituted. Further investigations were requested. Lupus anticoagulant was detected; anti-cardiolipin antibodies were negative; complement 3 normal, and complement 4 reduced at 0.12 g/L (reference range: 0.14-0.54 g/L). Hand and feet radiographs were unremarkable. At review in August 2016, a family history of antiphospholipidsyndromewasidentified (father).Repeatanti-phospholipid screenshowedapersistentpositive lupusanticoagulant;anti-cardiolipin antibodiesnegative.Complement,ESRandfullbloodcountwerenormal, other than mild lymphopenia (lymphocyte count: 0.96 x 10^9/L). She fell pregnant. Recommendations were made for close monitoring due to her family history of anti-phospholipid syndrome and positive anti-Ro antibodies. Discussion: This case represents a flare of systemic lupus erythematosus (SLE) post-partum with possible macrophage activation syndrome. Despite minimal signs of SLE prior to pregnancy, symptoms and signs dramaticallyworsenedpost-partum.Theimportanceofclosemonitoring of mother and baby during and after pregnancy has been highlighted. Regarding Ms A’s acute illness, macrophage activation syndrome is a likely cause of her rapid, severe deterioration. This is an auto-inflammatory syndrome which can be a life-threatening complication of rheumatic diseases; most commonly systemic juvenile idiopathic arthritis and adult-onset Still’s disease (Ravelli et al, 2012).Bonemarrow examination reveals macrophages which demonstrate haemophagocytic activity (Grom, Horne & de Benedetti, 2016). Bone marrow examination was not possible inthiscaseduetothecriticalconditionof thepatient. Keylearningpoints:Thoroughantenatalmonitoringofwomenwithpositive anti-Ro antibodies and lupus anticoagulant is required. Anti-coagulation is an important consideration in those with anti-phospholipid syndrome. Macrophage activation syndrome is an important differential diagnosis in patients presenting with sepsis-like illnesses, particularly in thosewithpre-existingrheumatologicalconditions.