Discussion:
In 1979 Risdall et al. individualized a new entity clinic characterized
by fever, hepato-splenomomegaly and pancytopenia. Lymphadenopathy, rash
and lung damage were often present. in this first description it was
also observed that the bone marrow and the lymph nodes were infiltrated
by macrophages of normal morphology, which phagocytized erythrocytes,
platelets and leukocytes.3
the autopsy of six fatal cases showed subarachnoid and hepatic
infiltration with hepatocytic necrosis. It was the first precise
description of hemophagocytosis syndrome.
The pathophysiology of HS has become better and better understood in
recent years thanks to the study of primary forms. it was recognized
that HS is due to a activation and / or cytotoxicity defect of CD8 T
cells and NK cells which produce large amounts of γ interferon which
leads to activation of macrophages in the bone marrow and
reticuloendothelial cells which in turn produce proinflammatory
cytokine.4
Indeed, plasma levels pro-inflammatory cytokines IL-1, IL-6, TNFα, IFNγ
M-CSF and IL-18 were elevated.
They are roughly divided into primary hemophagocytes lymphohistiocytosis
(HLH) and secondary hemophagocytic syndromes. Primary HLH is the
consequence of genetic mutations altering the cytotoxic function of the
natural killer (NK) and cytotoxic T cells and generally presents in
infancy and childhood. in primary HLH we find familial HLH (F HLH),
where patients have autosomal recessive mutations affecting Perforin
(FHLH2), MUNC 13-4 (UNC13D), STX11 (coding for syntaxin 11), and STXBP2
(coding for syntaxin-binding protein 2).5,6
Primary HLH also includes other inherited immunodeficiency syndromes
with hypo pigmentation such as Chédiak–Higashi syndrome, Griscelli
syndrome, and type II Hermansky–Pudlak syndrome.7
In the other hand, we have secondary HLH, they usually affect
adolescents and adults but, they are considered as reactive syndrome.
Most cases of secondary HLH are associated with “predisposing
condition” causing immune dysregulation, such as malignancy
(particularly lymphoma), immunodeficiency, or autoimmune disease, and/or
a “trigger”, most commonly infection such as Epstein–Barr virus
(EBV).8
In adults, infections represent the most prevalent triggers of HLH, with
increasing age, other causes are found like malignancies, primarily
lymphomas.9,10
\soutFor Concerning our patient, the clinical presentation was
concordant with infectious disease, the assessment found of fever and
jaundice. the etiological assessment found a viral hepatitis B and C
infection, however despite the antiviral treatment the persistence of
the fever pushed us to carry out more assessment at the research of HLH
which turned out to be positive.
In fact, the diagnosis of HLH in adults must be bone according to the
HLH-2004 diagnostic criteria in association with clinical judgment and
the patient’s history
In 1991, the Histiocyte Society suggests a standardized set of 5
diagnostic criteria for HLH used for the prospective HLH-94 clinical
trial. In 2004, a revision for these criteria was proposed and
validated, the new revision included more diagnosis criteria, for
positif diagnosis of HLH, individuals needed to meet 5 of 8 diagnostic
criteria.11,12
The positive diagnosis of HLH can be confirmed if a molecular diagnosis
consistent with HLH, or presence of 5 of the following criteria: Fever,
Splenomegaly, Cytopenias (affecting 2 of 3 lineages in the peripheral
blood), Hemoglobin less than 90 g/L (hemoglobin less than 100 g/L in
infants ,4 wk), Platelets less than 100 Giga/L, Neutrophils less than1
Giga/L, Hypertriglyceridemia and/or, hypofibrinogenemia, Fasting
triglycerides more than 3.0 mmol/L (ie, more than 265 mg/dL), Fibrinogen
more than1.5 g/L, Hemophagocytosis in bone marrow or spleen or lymph
nodes. No evidence of malignancy., Low or no NK cell activity (according
to local laboratory reference), Ferritin more than 500 mg/L, sCD25 (ie,
soluble IL-2 receptor) more than 2400 U/mL
Other diagnosis tools that are not part of the HLH-2004 criteria,
consist on hyperbilirubinemia, hepatomegaly, transaminitis (usually
found on patients with HLH), and elevated lactate dehydrogenase and
D-dimer levels, with the latter elevated on the majority of patient even
when international normalized ratio, partial thromboplastin time, and
fibrinogen are normal. These futures facilitates disctincting between
HLH and septic shock and conditions such as autoimmune hemolytic anemia,
and they can help for response evaluation to
therapy.13
For our patient, criteria for HLH were present, she was febrile, she had
a splenomegaly, cytopenia, hyperferritinemia, hypertriglyceridemia, and
specific images of hemophagositosis. For this patient exploring the
presence of peripheral hemophagocytosis has been proposed quickly for
identifying adult secondary HLH because she was admitted to our unit
with sepsis and pancytopenia.
The viral hepatitis are among the leading causes of chronic liver
disease worldwide and the first cause of cirrhosis in Africa. However,
The Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection is a
complex clinical entity that has an estimated worldwide prevalence of
1–15%.14 Most clinical studies have shown that
progression of disease is faster in HBV-HCV coinfected patients compared
to those with monoinfection, with high rates of decompensated
cirrhosis15 and increased incidence of Hepatocellular
carcinoma.16
Treatment in coinfected patients is complex, specially due to
interaction of the two viruses.
Until now, there are no clear treatment guidelines for HBV-HCV
coinfection. But many study showed good results with the new drugs like
direct acting antiviral agents.17
These treatment should be discuss for all candidates for chemotherapy
and immunosuppressive therapy with active viral hepatitis specially B.
Concerning adults with infection triggered-HLH the first line therapy
consists of antimicrobials. In these cases, the role of chemotherapy and
immunosuppression is not clear. Sometimes, systemic steroids can be
added to antimicrobials but its benefits are unknown due to lack of
data.18
In our case, in addition to the treatment for hepatitis the patient
underwent specific therapy for HLH according to HLH-94
protocol,19 with this treatment we obtained the
improvement of general condition, transfusion independence, decrease and
disparition of splenomegaly.