gms | German Medical Science

“Hemophagocytic Lymphohistiocytosis” (HLH), referred to as “macrophage activation syndrome” (MAS) in the context of systemic autoimmunity such as systemic Lupus Erythematosus (SLE) or adult onset Still’s disease (AOSD), is a rare and potentially life-threatening clinical condition. Aberrant macrophage and T cell hyper-activation and a systemic cytokine flare constitute the pathophysiological hallmarks of this syndrome and generate a sepsis-like, tissue-damaging, cytopenic phenotype. While primary/childhood cases of HLH route back to germline loss of function mutations in NK- or T-cell cytolytic pathway proteins, e.g. granzyme B, secondary/adult HLH might be triggered by environmental factors in the setting of an underlying autoimmune disease. This is most often observed in patients suffering from SLE or AOSD.

Once diagnosis is established, high dose corticosteroids are a mainstay of initial treatment. Unfortunately for adult onset secondary HLH, we lack standardized treatment protocols and outcome data is scarce on steroid refractory cases. In view of the relatively young age, the predominantly female patient population and the therapy-associated secondary damage of the cytotoxic agents used (e.g. etoposide, cyclophosphamide), there is disunity as to which immunosuppressive escalation hierarchy to choose. Aside from Ciclosporine-, Tacrolimus-, Etoposide-, Cyclophosphamide-, and anti-IL-1 based treatment protocols, favourable outcomes have been reported with the use of IvIG and therapeutic plasma exchange (TPE).

In this single centre experience, we report 7 cases of autoimmunity associated adult secondary HLH along with detailed treatment protocols. Besides the outcome, we emphasize the rationale of our chosen immunosuppressive escalation strategy. We pay particular attention to our resume on the early use of plasma exchange. And conclude on differential outcomes which appeared especially favourable with well established, yet long-term toxic agents, such as cyclophosphamide and etoposide, whereas targeted cytokine blockade appeared less effective.