Haemophagocytic lymphohistiocytosis with collapsing lupus podocytopathy as an unusual manifestation of systemic lupus erythematosus with APOL1 double-risk alleles

Abstract

Haemophagocytic lymphohistiocytosis (HLH) is a potentially life-threatening syndrome caused by excessive immune activation. Secondary HLH has been described in autoimmune diseases. We detail the case of a 28-year-old African American woman who developed HLH in the setting of systemic lupus erythematosus with collapsing lupus podocytopathy superimposed on mesangial proliferative lupus nephritis class II. Genotyping for APOL1 risk alleles revealed the presence of double (G1/G2) risk alleles. Our patient achieved a complete renal recovery and resolution of HLH within 1 month of treatment with steroids and mycophenolate mofetil, highlighting the importance of prompt, aggressive therapy.

Hemophagocytic Lymphohistiocytosis: Prevalence, Risk Factors, Outcome, and Outcome-related Factors in Adult Idiopathic Inflammatory Myopathies

“…MMF reversibly inhibits inosine monophosphate dehydrogenase, leading to decreased B cell and T cell proliferation and decreased cytokine production, which might consequently suppress the dysfunction in secondary HLH 45 . In addition, 2 SLE patients with secondary HLH were reported to be successfully treated with MMF, indicating the potential of MMF to cure secondary HLH in patients with CTD 46,47 . e significance, however, vanished aer adjusting for factors including infection and disease activity.…”

APOL1 Nephropathy: From Genetics to Clinical Applications

“…Provocative, indirect evidence raises the possibility of a complex relationship between JC viruses, APOL1 genotype, and kidney disease, although the precise nature of this interaction is not yet fully understood (67). Acute glomerulopathy has also been observed with hemophagocytic lymphohistiocytosis, a disease driven by aberrant cytokine production (68). Recently, cases of collapsing glomerulopathy have been reported in the setting of acute SARS-CoV-2 coronavirus infection, a transient high-cytokine state (69,70).…”

Histiocytic Glomerulopathy Associated With Hemophagocytic Lymphohistiocytosis

“… 12 , 13 The higher incidence in individuals of African descent suggests underlying genetic factors, such as the presence of nephropathic apolipoprotein L1 variants, as recently documented in a patient with HLH and collapsing lupus podocytopathy. 19 Close to two-thirds of reported patients with HLH-associated nephrotic syndrome died of HLH-associated multiorgan failure. 18 The outcomes of the few surviving patients were variable; some had remission of nephrotic syndrome, while others developed chronic kidney disease.…”