Haemophagocytic lymphohistiocytosis (HLH), also known as macrophage activation syndrome, is a nonmalignant disorder of immune regulation characterised by overproduction of cytokines and diminished immune surveillance. It may affect multiple organs and is one of few entities which demonstrate histiocytic emperipolesis on light microscopy.
It typically affects infants and children, as well as adult patients post-transplant 5.
The condition can be primary or secondary. The primary form is thought to have an autosomal recessive inheritance pattern, but with many instances of sporadic occurrence.
The secondary form may occur with several conditions such as 5:
- post-transplantation, particularly with PTLD
- infection: viral, bacterial, fungal, or parasitic
- drug exposure
- systemic lupus erythematosus
- Still disease
- Griscelli-Prunieras syndrome
- Chediak-Higashi syndrome
- EBV infection 2.3
- solid organ transplantation 10,11
- pulmonary hypertension 8
Systemic symptoms can be non-specific but patients can have pancytopenia, coagulopathy, and organomegaly,
Chest radiographs may show alveolar-interstitial opacities with pleural effusions, often with rapid evolution and resolution.
Hepatosplenomegaly, gallbladder wall thickening, hyperechoic kidneys and ascites are common abdominal findings.
Non-specific periventricular white-matter abnormalities, brain-volume loss and enlargement of extra-axial fluid spaces may be seen. Orbital myopathy has also been described.
History and etymology
It is thought to have been first reported by in 1952 by Farquhar and Claireaux who at that time called the disease familial hemophagocytic reticulosis 11.
- 1. Fitzgerald NE, MacClain KL. Imaging characteristics of hemophagocytic lymphohistiocytosis. Pediatr Radiol. 2003;33 (6): 392-401. doi:10.1007/s00247-003-0894-9 - Pubmed citation
- 2. Imashuku S, Kuriyama K, Sakai R et-al. Treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) in young adults: a report from the HLH study center. Med. Pediatr. Oncol. 2003;41 (2): 103-9. doi:10.1002/mpo.10314 - Pubmed citation
- 3. Imashuku S, Kuriyama K, Teramura T et-al. Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. J. Clin. Oncol. 2001;19 (10): 2665-73. Pubmed citation
- 4. Rooms L, Fitzgerald N, McClain KL. Hemophagocytic lymphohistiocytosis masquerading as child abuse: presentation of three cases and review of central nervous system findings in hemophagocytic lymphohistiocytosis. Pediatrics. 2003;111 (5 Pt 1): e636-40. Pubmed citation
- 5. Schmidt MH, Sung L, Shuckett BM. Hemophagocytic lymphohistiocytosis in children: abdominal US findings within 1 week of presentation. Radiology. 2004;230 (3): 685-9. doi:10.1148/radiol.2303030223 - Pubmed citation
- 6. Ozgen B, Karli-Oguz K, Sarikaya B et-al. Diffusion-weighted cranial MR imaging findings in a patient with hemophagocytic syndrome. AJNR Am J Neuroradiol. 2006;27 (6): 1312-4. AJNR Am J Neuroradiol (full text) - Pubmed citation
- 7. Joshi R, Phatarpekar A, Currimbhoy Z et-al. Haemophagocytic lymphohistiocytosis: a case series from Mumbai. Ann Trop Paediatr. 2011;31 (2): 135-40. doi:10.1179/1465328111Y.0000000009 - Pubmed citation
- 8. Gerard LM, Xing K, Sherifi I et-al. Adult hemophagocytic lymphohistiocytosis with severe pulmonary hypertension and a novel perforin gene mutation. Int. J. Hematol. 2012;95 (4): 445-50. doi:10.1007/s12185-012-1029-6 - Pubmed citation
- 9. Sevilla DW, Choi JK, Gong JZ. Mediastinal adenopathy, lung infiltrates, and hemophagocytosis: unusual manifestation of pediatric anaplastic large cell lymphoma: report of two cases. Am. J. Clin. Pathol. 2007;127 (3): 458-64. doi:10.1309/CQGUUF5BUVJE0YU5 - Pubmed citation
- 10. Diaz-Guzman E, Dong B, Hobbs SB et-al. Hemophagocytic lymphohistiocytosis after lung transplant: report of 2 cases and a literature review. Exp Clin Transplant. 2011;9 (3): 217-22. Pubmed citation
- 11. Oto T, Snell GI, Goto K et-al. Hemophagocytic syndrome: a rare but specific complication of lung transplantation. J. Thorac. Cardiovasc. Surg. 2010;140 (3): e58-9. doi:10.1016/j.jtcvs.2010.05.021 - Pubmed citation
- 11. Rosado, Flavia G. N., Kim, Annette S.. Hemophagocytic LymphohistiocytosisAn Update on Diagnosis and Pathogenesis. American Journal of Clinical Pathology. 139 (6): 713. doi:10.1309/AJCP4ZDKJ4ICOUAT