A Patient with Crohn's Disease who Presented with Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome

Abstract

Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is characterized with fever, purpura, anemia due to microangiopathic hemolysis, thrombocytopenia, kidney damage, and neurologic symptoms. The development of TTP/HUS during the course of inflammatory bowel diseases was rarely reported. However, coexistence of TTP/HUS and Crohn's disease in the same patient has not been reported previously. We herein present a case of TTP/HUS who presented with Crohn's disease. He responded to cyclosporine treatment.

• thrombotic thrombocytopenic purpura
• Crohn's disease
• cyclosporine

INTRODUCTION

Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) is a rare, acute, and frequently fatal disease. This syndrome is characterized with fever, purpura, thrombocytopenia, hemolytic anemia due to microangiopathy, renal disease, and neurological manifestations.¹ TTP/HUS was reported in the course of many diseases such as inflammatory diseases, malignancies, infections, and drug administrations.² TTP/HUS associated with Crohn's disease (CD) was rare previously.^3–5 However, TTP/HUS eventually occurred a long time after the diagnosis of CD in those cases. We herein report a patient with CD who presented with TTP/HUS. She responded well to cyclosporine treatment.

CASE REPORT

A 42-year-old woman was admitted to the emergency service with status epilepticus. Seizures were controlled within 48 h with phenytoin and midazolam. She had history of bloody diarrhea, abdominal pain, and anuria for the last 3 days. Her physical examination revealed fever (39.3°C), hypotension (90/50 mmHg), and tachycardia (117 bpm). She had confusion and also had purpuric lesions in her back and abdominal skin. In her laboratory examination, blood urea nitrogen (BUN) was 76 mg/dL, serum creatinine was 8.2 mg/dL, sodium was 130 mmol/L, potassium was 4.7 mmol/L, calcium was 8.4 mg/dL, albumin was 2.5 g/dL, serum glutamate oxalate transaminase (SGOT) was 52 U/L, serum glutamate pyruvate transaminase (SGPT) was 147 U/L, and lactate dehidrogenase (LDH) was 2491 U/L. Complete blood count revealed increased white blood cells (29.5 × 103), anemia (Hb = 8 g/dL), and thrombocytopenia (129 × 103). There were fragmented erythrocytes, drop cells, schistocytosis, and 5–7 thrombocytes in the peripheral blood smear. Anti nuclear antibody (ANA), anti-dsDNA, anticardiolipin antibodies, antiphospholipid antibodies, c-antineutrophil cytoplasmic antibody (c-ANCA), and p-ANCA were all negative. Immunoglobulin levels were all within normal ranges (IgG = 1210 mg/dL, IgA = 269 mg/dL, and IgM = 149 mg/dL). Prothrombin time and partial thromboplastin time were increased slightly and international normalized ratio (INR) was 1.12. No Escherichia coli O157 strain or Shigella was observed in culture of bloody diarrhea. Computerized tomography of brain was normal. ADAMTS-13 (A disintegrin-like and metalloprotease with thrombospondin type 1 repeats) assay could not be performed due to socioeconomic reasons. The patient was diagnosed as TTP/HUS and treated with plasmapheresis, hemodialysis, blood transfusion, and supportive care medications. The patient received daily plasmapheresis for six sessions. After 6 weeks of hospitalization, her mental status improved and anuria had resolved, but diarrhea persisted. In her 24-h urine analysis, 5.1 g/day proteinuria was detected. The colonoscopy that was performed because of persistent diarrhea showed multiple exudative ulcerations in the transverse colon. Histopathologic examination of tissue specimens revealed features of CD. Renal biopsy was performed because of massive proteinuria. The renal biopsy revealed swollen endothelial cells with luminal fibrin formation and fragmented erythrocytes within the lumens of arterioles. Patient was treated with 1 mg/kg/day methyl prednisolone and sulphasalazine with the diagnosis of CD and nephrotic syndrome due to TTP/HUS. Diarrhea improved after 7 days and serum creatinine levels decreased to 3.5 mg/dL without hemodialysis. In her clinical follow-up, her bloody diarrhea improved. The proteinuria was detected 5.1 g/day while urine output started. However, three months after urine output, serum creatinine was reduced to 2.2 mg/dl and proteinuria persisted about 4.2 g/day. Control colonoscopy revealed aphthous ulcerations from distal transverse colon to sigmoid colon. Cyclosporine A (CsA) (3 mg/kg/day) was added to her treatment because of lack of adequate response to previous treatment. Three months after CsA therapy, serum creatinine levels decreased to 1.6 mg/dL and urinary protein output decreased to 1.4 g/day. Additionally, colonoscopic appearance became normal.

DISCUSSION

The development mechanism of microthrombosis in TTP/HUS is still controversial. Autoimmune disorders or diseases associated with abnormal immune responses are among the most common triggering factors involved in the pathogenesis of TTP/HUS.^2,6 Thromboembolic events were occasionally reported in the course of CD.^7–9 Jackson et al. reported thrombotic episodes in 13% of patients with CD and speculated that the development of thrombosis could be associated with active bowel inflammation.¹⁰ Presumably, interaction between CD and autoimmune mechanisms might affect the pathogenesis of thrombosis. Several case reports have been reported previously with CD and TTP/HUS. In those cases, TTP/HUS usually appeared a long time after the diagnosis of CD.^3–5 On the contrary, our patient presented with a typical picture of TTP/HUS, including fever, renal failure, status epilepticus, microangiopathic anemia, and thrombocytopenia with purpuric lesions in her back and abdominal skin. Moreover, renal biopsy was compatible with TTP/HUS. Accordingly, she was diagnosed as TTP/HUS. She was also diagnosed as having CD after evaluation of persistent bloody diarrhea. To the best of our knowledge, this is the first CD patient who presented with the typical picture of TTP/HUS. Previously reported cases with TTP/HUS were treated classically with plasmapheresis and methyl prednisolone therapy. The improvement were achieved in three of these patients who treated with plasmapheresis and methyl prednisolone therapy.^3,4 In the last patient, splenectomy and complete proctectomy were performed because of unresponsiveness to classical treatment.⁵ In our patient although the symptoms of TTP/HUS could be controlled with plasmapheresis, the diarrhea and proteinuria did not resolve. Steroid and sulphasalazine treatments were initiated because of both nephrotic syndrome and active CD. However, her bowel symptoms were active and massive proteinuria persisted after 2 months of therapy. Thus, cyclosporine treatment was started. Proteinuria and renal functions improved, together with improvement of colonoscopic findings.

In conclusion, in patients with TTP/HUS presenting with persisted diarrhea, CD should be kept in mind in differential diagnosis. Additionally, we considered adding CsA for treatment of CD and nephrotic syndrome due to TTP/HUS in case of inadequate response to prednisolone and sulphasalazine treatments. CsA successfully improved colonoscopic finding of CD and decreased proteinuria and serum creatinine due to TTP/HUS.

Declaration of interest:The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.