Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature
Abstract
:1. Introduction
2. Patients and Methods
3. Results
3.1. Case #1
3.2. Case #2
4. Review of the Literature
4.1. Secondary HLH
4.2. Secondary AIC
5. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Feature | Cut Off |
---|---|
Fever | ≥38.5 °C |
Splenomegaly | |
Cytopenias | ≥2 cell lines |
—Hemoglobin * | <9 g/dL |
—Platelets * | <100 × 109/L |
—Neutrophils * | <1 × 109/L |
Hyperferritinemia | >500 mcg/L |
Hypofibrinogenemia or hypertriglyceridemia | <150 mg/dL >265 mg/dL |
Elevated soluble CD25 | >2400 U/mL |
Hemophagocytosis | Bone marrow, other tissues |
Reduced or absent NK cytotoxicity | |
Other features | |
Elevated transaminase and bilirubin | |
Elevated LDH | |
Elevated d-dimers | |
Cerebrospinal fluid pleocytosis and/or elevated protein |
Laboratory Tests | Day 1 | Day 7 | Normal Ranges |
---|---|---|---|
Hb (g/dL) | 6.5 | 8.9 | 13.5–17.5 |
PLT (10e9/L) | 22 | 12 | 130–400 |
WBC (10e9/L) | 3.9 | 14.7 | 4.8–10.8 |
Neutrophils (10e9/L) | 0.63 | 4.8 | 1.5–6.5 |
Lymphocytes (10e9/L) | 3.3 | 9.4 | 1.2–3.4 |
LDH (U/L) | 21759 | 17111 | 135–225 |
AST (U/L) | 927 | 424 | 8–48 |
ALT (U/L) | 101 | 43 | 9–59 |
GGT (U/L) | 61 | 116 | 8–61 |
ALP (U/L) | 95 | 137 | 40–129 |
Total bilirubin (mg/dL) | 1.99 | 0.12–1.1 | |
Unconjugated bilirubin (mg/dL) | 1.1 | 0–0.8 | |
Creatinine (mg/dL) | 1.6 | 1.48 | 0.72–1.18 |
PT ratio | 2.19 | 1.3 | 0.84–1.20 |
aPTT ratio | 1.27 | 0.78 | 0.86–1.2 |
CRP (mg/dL) | 4.28 | 1.33 | <0.5 |
Procalcitonin (mcg/L) | 11.2 | 2.82 | <0.05 |
Reticulocytes (10e12/L) | 0.022 | 0.097 | 0.02–0.10 |
Haptoglobin (mg/dL) | <10 | <10 | 30–200 |
Beta2-microglobulin (mg/L) | 15.2 | - | <0.2 |
Laboratory Tests | Admission | Week 3 | Week 6 | Normal Ranges |
---|---|---|---|---|
Hb (g/dL) | 8.8 | 8.8 | 7.8 | 13.5–17.5 |
PLT (10e9/L) | 147 | 50 | 19 | 130–400 |
WBC (10e9/L) | 4.7 | 4.6 | 18.8 | 4.8–10.8 |
Neutrophils (10e9/L) | 3.0 | 2.9 | 14.8 | 1.5–6.5 |
Lymphocytes (10e9/L) | 0.3 | 0.26 | 2.1 | 1.2–3.4 |
Reticulocytes (10e12/L) | 0.107 | - | - | 0.02–0.1 |
LDH (U/L) | 742 | 734 | 1390 | 135–225 |
Total bilirubin (mg/dL) | 1.2 | 2.13 | 1.99 | 0.12–1.1 |
Unconjugated bilirubin (mg/dL) | 1.0 | 1.64 | 1.4 | 0–0.8 |
Haptoglobin (mg/dL) | 45 | - | 24 | 30–200 |
Beta2-microglobulin (mg/dL) | 5.0 | - | - | <0.2 |
Creatinine (mg/dL) | 1.14 | 1.05 | 1.34 | 0.72–1.18 |
Ferritin (mcg/L) | 2740 | 3707 | 5507 | 30–400 |
PT ratio | 1.23 | 1.32 | 2.19 | 0.84–1.2 |
aPTT ratio | 0.86 | 0.88 | 2.4 | 0.86–1.2 |
Fibrinogen (mg/dL) | 353 | 162 | 53 | 165–350 |
Triglycerides (mg/dL) | 293 | 286 | 396 | <150 |
CRP (mg/dL) | 13.44 | 6.76 | 5.8 | <0.5 |
Secondary HLH | Frequency | Notes | Ref |
---|---|---|---|
Infections | <5% to 50% | Virus (CMV, EBV, influenza, adenovirus, dengue, SARS-CoV-2, HIV); bacteria (E. coli, mycoplasma, mycobacterium, tick-borne bacteria); fungi (histoplasma, aspergillus); parasites (malaria, Leishmania) | [11,12,13,14,15,16,17,18,19,20,21,22,23] |
Cancers | 10 to 47% 3% | Hematologic cancers, particularly lymphoma Solid cancers, particularly thymoma, ovarian and prostate cancer | [12,16,19,20,24] |
Autoimmune diseases | 10 to 40% | Systemic lupus erythematosus; rheumatoid arthritis; juvenile idiopathic arthritis; inflammatory bowel syndromes; Still’s disease; diabetes mellitus; sarcoidosis; psoriasis; Kawasaki and Kikuchi diseases; Steven-Johnson syndrome. | [12,19,20,23,25] |
Transplants | Up to 17% Case reports to 6% | Stem cell transplants Solid organ transplants | [12,19,26] |
Primary immunodeficiencies | Case series | Severe combined immunodeficiency; DiGeorge syndrome; Wiskott–Aldrich syndrome; chronic granulomatous disease | [12,19,27,28,29] |
Drugs | Case reports | Several drugs including targeted anti-cancer immunosuppressants and anti-microbial drugs | [12,23,30,31] |
Vaccinations | Case reports | Influenza and Bacillus Calmette Guerin vaccinations | [32,33] |
Secondary AIHA | Frequency | Notes | Ref |
Infections | Case reports to 20% | Parvovirus B19, HCV, HBV, HAV, HIV, Mycoplasma spp, tuberculosis, babesiosis, brucellosis, syphilis, EBV, respiratory syncytial virus | [34,35,36,37,38] |
Cancers | <5% to 30% | Solid tumors Hematologic cancers | [34,36,39,40] |
Autoimmune diseases | 1 to 14% | Systemic lupus erythematosus, systemic sclerosis, autoimmune thyroiditis, Sjogren syndrome, inflammatory bowel syndrome, autoimmune hepatitis/primary biliary cirrhosis | [41,42,43,44,45,46] |
Primary immunodeficiencies | 2 to > 50% | Autoimmune lymphoproliferative syndrome, common variable immunodeficiency, IgA deficiency | [36,47,48] |
Transplants | 2 to 15% | Stem cell transplants and solid organ transplants | [49,50,51,52,53] |
Drugs and vaccines | Case reports | Antibiotics, anti-fungal, antipsychotics, anti-convulsive, anti-neoplastic, anti-diabetics, and novel anti-cancers (Fludarabine, Bruton tyrosine kinase inhibitor, phosphoinositide 3-kinase and checkpoint inhibitors) | [6,7,34,36,54] |
AIHA | Membrane/ Enzyme Defects | CDA | PNH | TMA | Intravascular Devices | HLH | SIRS/Sepsis | |
---|---|---|---|---|---|---|---|---|
Hb | − to − − − | −/− − | − −/− − − | − −/− − − | − −/− − − | − | = to − − − | = to − |
Reticulocytes | − to + + + | − to + + + | −/= | − to + + | + | + | − to + | − |
Schistocytes | = | = | = | = | + + | + | = | = |
LDH | +/+ + | + | + | + + + | + + | + + | + to + + + | = to + |
Haptoglobin | − − − | − − − | − − | − − − | − | − − | = to + | +/+ + |
Bilirubin | + | + + | + | + | + | + | = to+ | = |
Ferritin | =/+ | + + | + + + | − to + | =/+ | =/+ | + + + | +/+ + |
PLT | =/− − | =/− | = | =/− | − − | =/− | = to − − − | + |
WBC | = | = | = | =/− | = | =/− | = to − − − | − to + + |
Hemosiderinuria | =/+ | = | = | + to + + + | =/+ | =/+ | = | = |
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Fattizzo, B.; Ferraresi, M.; Giannotta, J.A.; Barcellini, W. Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature. J. Clin. Med. 2021, 10, 870. https://doi.org/10.3390/jcm10040870
Fattizzo B, Ferraresi M, Giannotta JA, Barcellini W. Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature. Journal of Clinical Medicine. 2021; 10(4):870. https://doi.org/10.3390/jcm10040870
Chicago/Turabian StyleFattizzo, Bruno, Marta Ferraresi, Juri Alessandro Giannotta, and Wilma Barcellini. 2021. "Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature" Journal of Clinical Medicine 10, no. 4: 870. https://doi.org/10.3390/jcm10040870
APA StyleFattizzo, B., Ferraresi, M., Giannotta, J. A., & Barcellini, W. (2021). Secondary Hemophagocytic Lymphohistiocytosis and Autoimmune Cytopenias: Case Description and Review of the Literature. Journal of Clinical Medicine, 10(4), 870. https://doi.org/10.3390/jcm10040870