1. Prednisolone treated Mycophenolatemofetil + Prednisolone treated IgG4-related Acute Tubulo-interstitial Nephritis (TIN) in a 14 year old girl: Symptomatology, diagnosis, treatment and clinical course Mette Neland 1 MD, Niels Marcussen 2, MD, DMSc and Per Wittenhagen 1 MD. 1. Department of Paediatrics and 2. Department of Pathology, Odense University Hospital, Denmark. Contact: mette.neland@rsyd.dk Introduction IgG4-related disease is a presumed autoimmune disease, predominantly described in elderly males. IgG4-RD is a systemic fibro-inflammatory condition, that may involve almost any organ in the body. Manifestations in the kidney includes 1) Acute interstitial nephritis and 2) Membranous nephropathy. Discussion/conclusion The patient presented here had acute onset symptoms consistent with a systemic inflammatory disease with acute renal failure. In terms of the diagnostic criteria listed above: 1)There was kidney (organ) involvement with swelling and dysfunction 2)She had >10 IgG4 positive cells/hpf with IgG4/IgG ratio of 0.2, but 3)Her IgG4 and total IgG levels were normal (IgG4 <1,35 g/l) Clinically she rapidly responded to treatment with systemic steroids, but with a prompt relapse upon tapering - both as it has been described in adults. We postulate that this child has IgG4-related acute interstitial nephritis. IgG4-related kidney disease has not previously been described in children, but should be considered causative in children with TIN of unknown origin. Methods/Results Clinical presentation: A 14 year old female presented with a 3 week history of fever, fatigue, abdominal pain, anorexia, weight loss, arthralgia and mild acute kidney insufficiency (p-creatinine = 133 μmol/l). On examination she was normotensive, pale and generally unwell. Renal ultrasound showed bilaterally enlarged (13 cm long) and edematous kidneys. Hemoglobin was 5,4 mmol/l, C-reactive protein 52 mg/L, ESR was 65; ANCA, ANA, immunoglobulins, complement and IgG subclasses (IgG4 = 0,34g/l). She presented with low grade albuminuria of 60 mg/g (alb/crea) and no glycosuria. No underlying cause for acute tubular-interstitial nephritis was identified. Renal biopsy showed normal glomeruli, prominent interstitial fibrosis (with rare areas of storiform fibrosis), tubular atrophy and prominent acute interstitial inflammation consisting mainly of lymphocytes and plasma cells. Immunohistochemical staining revealed a IgG4/IgG-ratio of 0.2.and focally more than 10 cells IgG4 positive cells/hpf. Treatment: She responded quickly to prednisolone 50mg (1mg/kg/day). Her p-creatinine normalized and all her symptoms disappeared within days. Upon tapering of prednisolone, her p-creatinine rapidly rose. Prednisolone was subsequently increased and Mycophenolatemofetil (MMF) was added to the regimen in a dose of 1000mg x 2 /day, thus allowing us to taper her glucocorticoids completely after 11 months. After 24 months treatment, MMF was discontinued without evidence of recurrence and a stable p-creatinine (60 μmol/l).. H. C. Andersen Børnehospital AB CD Fig. A: HEx20: Many plasma cells were focally present in the infiltrate. HEx200. Fig. C: IgGx20: Immunohistochemical staining for IgG demonstrating the presence of many IgG positive lymphocytes and plasma cells. Fig. B: MTx20: Interstitial fibrosis accompanied the infiltrate. Masson-Trichrom x200. Fig. D: IgG4x20: Immunohistochemical staining for IgG4 demonstrating the focal presence of IgG4 positive cells. Immunoflourescence without positive stainning. CriterionThe Mayo Clinic, criteriaJapanese Society of Nephrology, Criteria HistologyPlasma cell-rich TIN with >10 IgG4+ plasma cells/HPF field in the most concentrated field (mandatory criterion) Dense lymphoplasmacytic infiltrate with >10 IgG4+ plasma cells/HPF and/or IgG4/IgG+ plasma cell ratio of >40 % TBM immune complex deposits by immunofluorescence, immunohistochemistry, and/or electron microscopy Characteristic storiform fibrosis ImagingSmall peripheral low-attenuation cortical nodules, round or wedge- shapped lesions, or diffuse patchy involvement Multiple low-density lesions on enhanced CT, diffuse kidney enlargement, hypovascular solitary nodule, hypertrophic lesion of the renal pelvic wall SerologyElevated serum IgG4 or total IgG level, IgG4 > 1,35g/l Elevated serum IgG4 or total IgG level, IgG4 > 1,35g/l Clinical features NoneClinical or laboratory evidence of kidney damage Other organ involvement Characteristic findings of IgG4-RD in other organs Definite IgG4-TIN The histologic feature and at least one other feature from imaging, serology or other organ involvement The histologic feature (a and b) and at least two of other features from imaging, serology or other organ involvement Reference: Tang,X et al. Diagn Pathol, 2015, 10, 83