Case 1: 9-year-old female with rash and oral ulcer

Alexandre Belot

Alisson is 9 years old and came to the outpatient unit with a rash and oral ulcer. Her past medical history highlighted two invasive infections (meningitidis and pneumonia). She had no muscular weakness, no lymphoproliferative disease and no fever.

Her laboratory exams revealed: WBC: 2.5 G/L, with PNM=1.2G/L, Hb = 10 g/dl, Platelet = 135G/L, CRP = 10 mg/L. CPK and aldolase were within normal values. Serology for Epstein-Barr Virus, parvovirus B19 and measles were negative.

Autoimmune check-up showed: ANA+ 1/1280, C3 and C4 normal, anti-dsDNA negative, anti SSA+ >8. The dosage of immunoglobulins was normal (including subclasses). She further developed severe systemic disease with lupus nephritis, white matter lesions at the cerebral MRI.

Complement CH50 was dramatically decreased and her C1q level was undetectable.

Discussion Points

• Explore complement deficiency in juvenile systemic lupus erythematosus (SLE)

• Discuss monogenic SLE

Discussion Points Case 2: 13-year-old female with skin rash and chilblain

Alexandre Belot

Jade is 13 years old and has been recently diagnosed with juvenile SLE. Her past medical history revealed a pervasive developmental disorder with features of autism and mental delay. Her parents are first cousins. Her first symptoms were skin rash, chilblain. Following first-line therapy with hydroxychloroquine and topical steroids, she developed a polyarthritis with hepatitis and leukopenia. Abdominal sonography was normal. Autoantibodies for autoimmune liver disease (dot hepatitis) were negative. Treatment with steroids and methotrexate was introduced and effective on the joints. Further genetic exploration revealed a biallelic mutation of TREX1. Later on, she was treated with a JAK inhibitor in addition to methotrexate resulting in a positive outcome.

Discussion Points

• Type I interferon in juvenile SLE

• Interferonopathies

Discussion Points Case 3: 14-year-old male with haematuria and renal colic

Alexandre Belot

Michael presented a macroscopic hematuria with renal colic at the age of 14 years old. Sonography revealed a left nephromegaly without evidence of urinary tract obstruction. A CT scan showed a left renal venous thrombosis. Initial work-up identified a triple positivity for lupus anticoagulant, anti-B2 Gp-I and anti-cardiolipin antibodies. Anticoagulant therapy was initiated. dsDNA and ANA were negative and complement was normal. Six months later, the hematuria had completely disappeared, according to a urine dipstick test, but proteinuria was still present with a protein:creatinine ratio of 120 mg/mmol in the urine. A new doppler sonography and CT scan showed the absence of perfusion in the left kidney.

Considering the proteinuria, a percutaneous biopsy was performed on the contralateral kidney and histology revealed Class V lupus nephritis. Notably, autoantibodies and complement were still normal. Rituximab and ACE inhibitors were introduced, and proteinuria rapidly disappeared.

Discussion Points

• How to explore APS in children

• Management of thrombosis in pediatric autoimmune diseases

Discussion Points Case 4: Anti-histone antibodies: does it always mean drug-induced lupus erythematosus?

Rolando Cimaz

A South-American 14-year-old girl presented with arthralgia, weakness and alopecia. As she was under antiepileptic treatment since she was 5 years old, on suspicion of drug-induced lupus erythematosus (DILE) anti-histone antibodies were dosed and showed positive results. She presented with mild anemia, leukopenia, hypocomplementemia, ANA, anti-dsDNA and LAC positivity. The antiepileptic therapy was initially modified and then, as no more crises were present, interrupted. However, anemia, leukopenia, hypocomplementemia, ANA and anti-dsDNA persisted, and the diagnosis of idiopathic systemic lupus erythematosus (SLE) was made. After treatment with hydroxychloroquine and low dose prednisone the girl clinically improved and her laboratory results normalized. This case report is suggestive of the complexity in differentiating SLE and DILE and underlines the importance of a long and careful follow-up.

Discussion Points

• Medications that can trigger lupus symptomatology

• Triggers of lupus or of lupus-like disease (autoimmunity in general) with TNF inhibitors used for arthritis

• Risks of prescribing such medications (i.e. anti-TNF) in patients with inflammatory arthritis and pre-existing autoantibodies or a family history of autoimmune disease

Discussion Points Case 5: Bleeding and thrombosis in juvenile systemic lupus erythematosus

Rolando Cimaz

A young girl with immune thrombocytopenic purpura was also found to have antiphospholipid antibody syndrome. This case describes the complexity of therapeutic management linked to the risk of bleeding and thrombosis.

Irene is 15-year-old. In recent hours she has experienced intermittent claudication and lower right limb pain. Her physical exam reveals swelling and tenderness of right calf, pain to compression and mobilization of right foot. Laboratory tests reveal WBC 21.610 (N 77%); Hb 13.1 g/dl; PLT 91000/mmc; aPTT 48.4 sec, PT 99%; fibrinogen 236 mg/dl; D-Dimer 0.59 mg/L. Ultrasound revealed thrombosis.

Past medical history showed that 8 months before she had suffered from severe metrorrhagia. Laboratory tests had shown: PLT 7000, Hb 10.2 g/dl, Coombs direct test +, PT 1.18, aPTT 76 sec; IgM e IgG anticardiolipin +. Therapy consisted in intravenous immunoglobulin (two infusions) and then oral steroids. Five relapses occurred, and laboratory showed: ANA+ (1:160), ENA -, anticardiolipin -, C3 85, C4 7.5, LAC +. Repeat laboratory test showed ANA+, ENA-, anticardiolipin +, anti-b2 glycoprotein -, LAC +.

Discussion Points

• For thrombosis Heparin 6000U/x2/day. For how long? And for thrombocytopenia? Oral steroids (2 mg/kg/day); Mycophenolate mofetil (750 mg/m² x 2/day). But despite this therapy, she relapsed. So > rituximab 750 mg/m2/2 weeks. For SLE hydroxychloroquine was given.

Learning Objectives

• Distinguish between idiopathic and drug-induced SLE

• Describe the treatment of APS in children

• Discuss treatment options for hematologic SLE