New review pushes for clearer veterinary criteria for HLH

A newly published review in Veterinary Clinical Pathology is putting fresh attention on one of small animal medicine’s most difficult inflammatory syndromes: hemophagocytic syndrome, also referred to as hemophagocytic lymphohistiocytosis, or macrophage activation syndrome. In the paper, published online October 19, 2026, Purdue’s Joanne B. Messick describes HLH/HPS as a life-threatening state of immune dysregulation marked by cytokine overproduction, hemophagocytosis, cytopenias, and multiorgan dysfunction, and argues that veterinary medicine still lacks the standardized criteria and validated biomarkers that guide diagnosis in human patients. (lifescience.net)

That gap is the main story. Human medicine has spent years refining HLH/MAS recognition and management, including formal diagnostic frameworks and multidisciplinary guidance that stress rapid recognition, systematic evaluation of triggers, and early treatment of both hyperinflammation and the underlying cause. By contrast, veterinary clinicians are still working from scattered case reports, small case series, and extrapolation from human medicine when faced with dogs or cats showing fever, cytopenias, coagulopathy, organ dysfunction, or marrow hemophagocytosis. (sciencedirect.com)

Messick’s review aims to consolidate that fragmented literature. According to the abstract, it covers pathogenesis, clinical and clinicopathologic features, diagnosis, and differential diagnoses, with emphasis on dogs and cats, and proposes a framework for standardized canine diagnostic criteria. The article also evaluates representative canine cases of secondary HPS and hemophagocytic histiocytic sarcoma to illustrate how easily these entities can overlap diagnostically. That distinction matters because hemophagocytic syndrome is generally a reactive hyperinflammatory process tied to an underlying trigger, while hemophagocytic histiocytic sarcoma is an aggressive macrophage-lineage malignancy with its own immunophenotypic profile, including CD11d positivity in classic descriptions. (lifescience.net)

The veterinary backdrop helps explain why a review like this is timely. Earlier reports identified hemophagocytic syndrome in dogs and cats with infectious, neoplastic, immune-mediated, and metabolic disease, and highlighted bone marrow cytology as an important diagnostic aid when bloodwork shows unexplained bicytopenia or pancytopenia. A 24-case canine series from 1996 to 2005 used bicytopenia or pancytopenia plus more than 2% hemophagocytic macrophages in marrow aspirates as inclusion criteria, underscoring how heavily diagnosis has depended on morphology rather than validated biomarker panels. Other canine reports have described severe presentations including disseminated intravascular coagulation and rapid clinical decline. (pubmed.ncbi.nlm.nih.gov)

There’s also evidence that the profession has been building toward this discussion. Messick presented “In the Midst of a Cytokine Storm” as part of the ASVCP current topics session at the 2024 ACVP/ASVCP annual meeting, suggesting the review grew out of a broader effort to frame histiocyte- and macrophage-driven disease for clinical pathologists and diagnosticians. Recent related literature in Veterinary Clinical Pathology, including case reports involving hemophagocytic syndromes and feline lymphomas with hemophagocytosis, points to continued interest in how these disorders are recognized across species and disease categories. (acvp.org)

Why it matters: For veterinary professionals, this review is important because it reframes HLH/HPS/MAS as a syndrome that may be hiding in plain sight among cases labeled sepsis, immune-mediated cytopenia, marrow disease, or disseminated neoplasia. The practical challenge is not just identifying hemophagocytosis, which human critical care literature notes can be inconsistent and nonspecific, but integrating marrow morphology with CBC changes, inflammatory markers, imaging, and, where available, immunophenotyping or molecular testing. If the field moves toward more standardized canine criteria, it could improve case recognition, make studies more comparable, and help clinicians separate reactive cytokine storm syndromes from hemophagocytic histiocytic sarcoma earlier in the workup. (pmc.ncbi.nlm.nih.gov)

Expert reaction outside the paper itself appears limited so far, which isn’t unusual for a just-published specialty review. Still, the article’s publication in the official journal of the American Society for Veterinary Clinical Pathology gives it weight within diagnostic pathology and laboratory medicine circles, especially because it is synthesizing a problem that has long been recognized as serious but inconsistently defined in companion animals. (onlinelibrary.wiley.com)

What to watch: The next step is whether researchers turn this proposed framework into prospective validation studies, especially around ferritin, marrow thresholds, lineage markers, and differentiation from hemophagocytic histiocytic sarcoma, and whether cats eventually get species-specific criteria rather than being folded into canine-first approaches. (lifescience.net)