An unusual association between hemophagocytic lymphohistiocytosis, mixed connective tissue disease, and autoimmune hemolytic anemia

Abstract

Rationale:In the adult patient, hemophagocytic lymphohistiocytosis (HLH) is uncommon and frequently difficult to diagnose due to its nonspecific presentation and numerous complications.Patient concerns:Herein, we present the case of a 25-year-old female who initially presented for evaluation of persistent fevers and fatigue. She was found to have splenomegaly, generalized lymphadenopathy, pancytopenia, and acute hepatic failure.Diagnoses, Interventions, and Outcomes:Her course was further complicated by the development of nephrotic syndrome and autoimmune hemolytic anemia (AIHA). Antinuclear antibody and ribonucleoprotein were positive, with concurrent physical examination findings, indicating underlying mixed connective tissue disease (MCTD). Ferritin was greater than 40,000 ng/dL. Viral studies, including hepatitis A, B, and C, cytomegalovirus, and Epstein–Barr virus were negative. On the basis of her clinical presentation, a diagnosis of HLH secondary to MCTD was made. This was later confirmed on liver biopsy. She was started on high-dose prednisone and her symptoms completely resolved. She was then transitioned to azathioprine, hydroxychloroquine, prophylactic antibiotics, and a prednisone taper for long-term management.Lessons:This case is notable for the association of both AIHA and MCTD with HLH, providing support for a possible relationship between these 3 conditions.

Autoimmune hemolytic anemia: An unusual presentation of hemophagocytic lymphohistiocytosis in a pediatric post–liver transplant patient

“…Although there are few reports of pediatric post‐LT associated HLH, the presenting symptom of AIHA has not yet been described. There are, however, multiple reports in nontransplant patients of AIHA associated with HLH in the setting of autoimmune disease and in pregnancy …”

“…There are, however, multiple reports in nontransplant patients of AIHA associated with HLH in the setting of autoimmune disease and in pregnancy. [13][14][15] AIHA can be seen independently or in connection with SOT.…”

A Fatal Case of Dengue-Associated Hemophagocytic Lymphohistiocytosis and Retroperitoneal Hematoma in a Patient With Autoimmune Hemolytic Anemia

“…We believed that the immunologic mechanisms involved in the pathogenesis of AIHA could predispose to HLH in this case. An unusual association between HLH, mixed connective tissue disease, and AIHA was reported previously by Kelkar et al [11]. However, the development of HLH associated with dengue infection and AIHA has not been reported in the past.…”

Acute liver failure secondary to severe systemic disease from fatal hemophagocytic lymphohistiocytosis: Case report and systematic literature review

“…HLH has primary (genetic) etiologies, which usually manifest in infants with genetic immunologic mutations[ 7 ], and secondary (acquired) etiologies which typically manifest in older children or adults. Secondary etiologies include infection, especially with Epstein-Barr virus[ 8 , 9 ] or herpes simplex virus-1[ 10 ]; malignancy; or autoimmune diseases (called macrophage activation syndrome when HLH is associated with autoimmune diseases)[ 11 ]. The common denominator in all acquired etiologies is disrupted immune homeostasis.…”