Concomitant Hemophagocytic Lymphohistiocytosis and Cytomegalovirus Disease: A Case Based Systemic Review

Abstract

BackgroundHemophagocytic lymphohistiocytosis (HLH) is an immune mediated life-threatening condition. It is driven by an overactivation of the immune system and causes inflammatory tissue damage potentially leading to organ failure and death. Primary HLH is caused by genetic mutations, while secondary HLH is triggered by external factors. Viral infections are a well-known cause of secondary HLH. Cytomegalovirus (CMV) is a virus in the herpes family known to cause HLH in rare cases.MethodsWe report a recent case of CMV-induced HLH, followed by a systematic review of described cases of this rare disease entity, through a structured search in the medical database PubMed. All articles were assessed on a predetermined set of inclusion criteria.ResultsA total of 74 patients (age > 18 years) with CMV-related HLH were identified, 29 men, 42 women, and three patients with unspecified gender. Median age was 37.5 years (range 18–80). Sixty-six patients (88%) had one or more comorbid conditions and 22 patients (30%) had inflammatory bowel disease (IBD), the most frequent comorbidity. Forty patients (54%) received some form of immunomodulating treatment prior to HLH development. The general treatment approach was in general dual, consisting of antiviral treatment and specific immunomodulating HLH treatment approaches. Treatment outcome was at 77% survival, while 23% had fatal outcome.ConclusionThe findings highlight the importance of early diagnostic work up and treatment intervention. Ability to recognize the characteristic clinical traits and perform specific HLH diagnostic workup are key factors to ensure targeted diagnostic work and treatment intervention for this patient group.

Secondary haemophagocytic lymphohistiocytosis in a patient with new-onset systemic lupus erythematosus: the challenges of timely diagnosis and successful treatment

“…In patients with CMV-induced HLH, precipitating upper respiratory symptoms such as non-productive cough and malaise can be mild or even absent, followed by persistent fevers, cytopenias, and elevated serum ferritin with or without high serum triglyceride or low fibrinogen 19. Lymphadenopathy and splenomegaly can be absent in around 35% of patients 20. Positive viral serologies with IgG and IgM and positive CMV-DNA PCR (generally greater than 10 000 copies/mL) indicating active infection are usually seen 20–22.…”

“…Lymphadenopathy and splenomegaly can be absent in around 35% of patients 20. Positive viral serologies with IgG and IgM and positive CMV-DNA PCR (generally greater than 10 000 copies/mL) indicating active infection are usually seen 20–22. In CMV-induced HLH, most patients receive both antiviral and immunosuppressive therapies (usually high-dose steroids such as dexamethasone), with or without the chemotherapy etoposide, with an expected response in usually 3–10 days 17 19 23.…”

New sights of low dose IL‐2: Restoration of immune homeostasis for viral infection

“…Here, we are focusing on virus-associated haemophagocytic syndrome (VAHS). Recent research has shown that several types of viruses, including EBV [32,33], CMV [34], HIV [35], parainfluenza virus [36], human herpesvirus Type 6 (HHV-6) [37] and other types of viruses [38] can trigger HLH. Among VAHS, EBV is major cause of HLH, and EBV-HLH is associated with a high risk of death and multi-organ failure.…”

Cytomegalovirus-Induced Hemophagocytic Lymphohistiocytosis in an Immunocompromised Patient with Inflammatory Bowel Disease

“…Primary, or familial HLH, is caused by inherited genetic mutations that disrupt the function of cytotoxic T cells and natural killer (NK) cells [ 2 ]. Symptoms are often severe and present early in life [ 3 ]. Secondary or acquired HLH is induced by a variety of triggers including infection, malignancy, autoimmunity, and immunosuppression [ 2 , 3 ].…”