{"id":16143,"date":"2025-08-09T12:31:58","date_gmt":"2025-08-09T12:31:58","guid":{"rendered":"https:\/\/introlab.net\/hemofagocitna-limfohistiocitoza-redak-ali-ozbiljan-poremecaj-imunog-sistema\/"},"modified":"2025-08-10T14:35:48","modified_gmt":"2025-08-10T14:35:48","slug":"hemophagocytic-lymphohistiocytosis-rare-but-serious-immune-disorder","status":"publish","type":"post","link":"https:\/\/staging-introlab.dev-digitaldot.com\/en\/hemophagocytic-lymphohistiocytosis-rare-but-serious-immune-disorder\/","title":{"rendered":"Hemophagocytic lymphohistiocytosis \u2013 Rare but serious immune disorder"},"content":{"rendered":"<p>HLH is a rare disease that affects between one in 20,000 and one in 60,000 newborns each year, and it is estimated that around 250 people in Serbia live with this diagnosis. <em>Hemophagocytic lymphohistiocytosis (HLH) is a condition in which the immune system loses its ability to precisely regulate its defensive responses.<\/em> In a healthy body, immune cells recognize and destroy pathogens while protecting healthy tissues. In HLH, immune cells &#8211; primarily T lymphocytes and macrophages &#8211; begin attacking healthy cells as well, triggering systemic inflammation. This reaction can damage the <em>liver, spleen, bone marrow, skin, and nervous system<\/em>. Although rare, the disease can occur at any age. Because of its rapid progression and potential for severe complications,<strong> any suspicion of HLH requires urgent medical evaluation.<\/strong><br \/>\n<!--more--><\/p>\n<h2>What is hemophagocytic lymphohistiocytosis (HLH)<\/h2>\n<p>HLH is a <strong>syndrome of excessive immune activity.<\/strong> Macrophages and lymphocytes, which under normal conditions destroy pathogens, produce excessive amounts of cytokines in <strong>HLH\u2014molecules that trigger inflammation.<\/strong> This reaction creates a condition known as a<em> \u201ccytokine storm.\u201d<\/em> In this state, inflammation spreads throughout the body, affecting the<em> blood, liver, spleen, skin, and nervous system.<\/em> Without treatment, a cytokine storm can lead to organ failure and death.<\/p>\n<figure id=\"attachment_16113\" aria-describedby=\"caption-attachment-16113\" style=\"width: 770px\" class=\"wp-caption aligncenter\"><img decoding=\"async\" class=\"wp-image-16113 size-full\" src=\"https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-karolina-5.jpg\" alt=\"A tired woman searching on her computer what hemophagocytic lymphohistiocytosis is\" width=\"770\" height=\"350\" srcset=\"https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-karolina-5.jpg 770w, https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-karolina-5-300x136.jpg 300w, https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-karolina-5-768x349.jpg 768w\" sizes=\"(max-width: 770px) 100vw, 770px\" \/><figcaption id=\"caption-attachment-16113\" class=\"wp-caption-text\">Hemophagocytic lymphohistiocytosis is a rare but serious immune system disorder.<\/figcaption><\/figure>\n<h2>What types of HLH are there?<\/h2>\n<p>There are two main forms:<\/p>\n<ul>\n<li><strong>Primary (hereditary)<\/strong> \u2013 caused by mutations in genes that regulate the function of the immune system, usually occurring in children, often within the first months of life.<\/li>\n<li><strong>Secondary (acquired)<\/strong> \u2013 develops due to external factors such as infections, autoimmune diseases, malignancies, or strong immune reactions after organ transplantation.<\/li>\n<\/ul>\n<h2>What causes HLH and who is at risk?<\/h2>\n<p>Primary HLH is an <strong><a href=\"https:\/\/staging-introlab.dev-digitaldot.com\/en\/hereditary-diseases-and-disorders-you-might-not-know-about\/\">inherited form of the disease<\/a> that usually appears in children<\/strong>, often within the first months or years of life. It is passed down in an autosomal recessive pattern, meaning <em>a child must inherit a mutated gene from both parents.<\/em> The most common mutations occur in the<em> PRF1, UNC13D, STX11, STXBP2, RAB27, and XLP genes.<\/em> These genetic changes impair the normal communication and function of immune cells, leading to uncontrolled inflammation.<\/p>\n<p>Secondary HLH can occur at any age and is often triggered by:<\/p>\n<ul>\n<li><strong>Viral infections<\/strong> (<a href=\"https:\/\/staging-introlab.dev-digitaldot.com\/en\/epstein-barr-virus-ebv-nasopharyngeal-swab-blood-cerebrospinal-fluid-synovial-fluid-amniotic-fluid-effusion-sputum\/\">Epstein\u2013Barr virus<\/a>, cytomegalovirus, HIV, influenza)<\/li>\n<li><strong>Bacterial infections<\/strong> (tuberculosis, salmonella, listeria, sepsis)<\/li>\n<li><strong>Parasitic infections<\/strong> (malaria, leishmaniasis)<\/li>\n<li><strong>Autoimmune diseases<\/strong> (systemic lupus erythematosus, rheumatoid arthritis, polyarteritis nodosa, sarcoidosis, systemic sclerosis, Sj\u00f6gren\u2019s syndrome, Kawasaki disease)<\/li>\n<li><strong>Blood cancers<\/strong> (lymphomas, leukemias)<\/li>\n<li><strong>Severe immune reactions after organ or bone marrow transplantation<\/strong> (e.g., kidney or liver transplant)<\/li>\n<li><strong>Rare adverse reactions to certain medications<\/strong> (especially in immunologically sensitive patients)<\/li>\n<\/ul>\n<p><strong>Who is at risk for HLH?<\/strong><\/p>\n<ul>\n<li>People with a family history of HLH or genetic mutations associated with the disease<\/li>\n<li>Patients with severe immunodeficiencies<\/li>\n<li>Children and young adults (primary HLH is more common in children)<\/li>\n<li>Males (slight predominance in familial HLH)<\/li>\n<li>People living in regions with frequent infections that can trigger HLH<\/li>\n<li>Patients with autoimmune diseases, malignancies, or severe infections<\/li>\n<\/ul>\n<h2>What are the symptoms of HLH?<\/h2>\n<p>HLH is difficult to recognize because its symptoms <strong>resemble those of severe infections or other inflammatory diseases.<\/strong><\/p>\n<p>Common early symptoms include:<\/p>\n<ul>\n<li>Fever above 38\u00b0C (100.4\u00b0F) lasting more than 7 days and not responding to standard treatment<\/li>\n<li>Enlarged spleen (splenomegaly) and liver (hepatomegaly)<\/li>\n<li>Abdominal pain or a feeling of pressure in the abdomen<\/li>\n<li>Skin rash or redness<\/li>\n<li>Marked fatigue, weakness, and loss of appetite<\/li>\n<li>Rapid weight loss<\/li>\n<\/ul>\n<p>Symptoms of advanced disease:<\/p>\n<ul>\n<li>Anemia, leukopenia, thrombocytopenia (cytopenia in more than two blood cell lines)<\/li>\n<li><a href=\"https:\/\/staging-introlab.dev-digitaldot.com\/en\/how-and-why-blood-clots-form\/\">Blood clotting disorders<\/a>, nosebleeds or gum bleeding, bruising<\/li>\n<li>Jaundice and signs of liver damage<\/li>\n<li>Difficulty breathing due to pneumonia or fluid accumulation<\/li>\n<li>Neurological symptoms: seizures, confusion, behavioral changes, vision problems, altered consciousness<\/li>\n<\/ul>\n<p>In severe cases, symptoms can develop within a few days and require urgent hospitalization<\/p>\n<h2>How is HLH diagnosed?<\/h2>\n<p>Diagnosing HLH involves:<\/p>\n<ul>\n<li>A detailed clinical examination and assessment of symptoms<\/li>\n<li>Laboratory analysis of blood and biochemical parameters<\/li>\n<li>Microscopic examination of bone marrow or other tissue samples<\/li>\n<li><a href=\"https:\/\/staging-introlab.dev-digitaldot.com\/en\/genetic-tests\/\">Genetic testing<\/a>, if needed, to confirm mutations<\/li>\n<\/ul>\n<p>HLH is diagnosed if there is a confirmed mutation associated with the disease or if the patient meets at least 5 out of 8 HLH criteria:<\/p>\n<ul>\n<li><strong>Fever<\/strong> &gt;38.5\u00b0C lasting more than 7 days<\/li>\n<li><strong>Splenomegaly<\/strong> (enlarged spleen &gt;3 cm below the costal margin)<\/li>\n<li><strong>Cytopenia<\/strong> in at least two blood cell lines (Hb &lt;9 g\/dl, neutrophils &lt;1,000\/\u03bcL, platelets &lt;100,000\/\u03bcL)<\/li>\n<li><strong>Hypertriglyceridemia<\/strong> (&gt;2.0 mmol\/L) or hypofibrinogenemia (&lt;1.5 g\/L)<\/li>\n<li><strong>Hemophagocytosis<\/strong> in bone marrow, spleen, or lymph nodes<\/li>\n<li><strong>Decreased or absent <a href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39273034\/\" target=\"_blank\" rel=\"noopener\">NK cell activity<\/a><\/strong><\/li>\n<li><strong>Serum ferritin<\/strong> &gt;500 \u03bcg\/L (often much higher)<\/li>\n<li><strong>Elevated soluble<\/strong> IL-2 receptor (CD25) (&gt;2,400 U\/mL)<\/li>\n<\/ul>\n<figure id=\"attachment_16116\" aria-describedby=\"caption-attachment-16116\" style=\"width: 770px\" class=\"wp-caption aligncenter\"><img decoding=\"async\" class=\"wp-image-16116 size-full\" src=\"https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-polina-tankil-1.jpg\" alt=\"A person in a blue sweater is holding a thermometer\" width=\"770\" height=\"350\" srcset=\"https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-polina-tankil-1.jpg 770w, https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-polina-tankil-1-300x136.jpg 300w, https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-polina-tankil-1-768x349.jpg 768w\" sizes=\"(max-width: 770px) 100vw, 770px\" \/><figcaption id=\"caption-attachment-16116\" class=\"wp-caption-text\">A prolonged high fever may be a sign of HLH.<\/figcaption><\/figure>\n<h2>How is HLH treated?<\/h2>\n<p>Treatment depends on the underlying cause, but the goal is always the same \u2014 <em>to suppress the excessive immune response and prevent organ damage.<\/em><\/p>\n<p>Standard therapies include:<\/p>\n<ul>\n<li><strong>Corticosteroids<\/strong> \u2013 reduce inflammation and immune activity<\/li>\n<li><strong>Etoposide<\/strong> \u2013 a cytostatic drug that suppresses excessive activity of lymphocytes and macrophages<\/li>\n<li><strong>Cyclosporine A<\/strong> \u2013 an immunosuppressant that inhibits T cells<\/li>\n<li><strong>Intravenous immunoglobulins (IVIG)<\/strong> \u2013 help modulate the immune response<\/li>\n<li><strong>Antimicrobial drugs<\/strong> \u2013 specifically treat infections that have triggered HLH<\/li>\n<\/ul>\n<p>Specialized approaches:<\/p>\n<ul>\n<li><strong>Emapalumab<\/strong> \u2013 a monoclonal antibody that blocks interferon-gamma, approved in some countries for primary HLH<\/li>\n<li><strong>Anakinra<\/strong> \u2013 an interleukin-1 blocker used in HLH associated with autoimmune diseases<\/li>\n<li><strong>Bone marrow transplantation<\/strong> \u2013 the only permanent treatment for primary HLH, and sometimes used in severe cases of secondary HLH<\/li>\n<\/ul>\n<p>Treatment is carried out in specialized hematology or immunology centers, with intensive monitoring<\/p>\n<h2>What complications can HLH cause?<\/h2>\n<p>Without adequate treatment, HLH can lead to:<\/p>\n<ul>\n<li>Liver, kidney, or lung failure<\/li>\n<li>Brain damage and permanent neurological consequences<\/li>\n<li>Sepsis and severe infections<\/li>\n<li>Coagulopathy with massive bleeding<\/li>\n<\/ul>\n<p>Even with therapy, <em>patients may develop chronic complications<\/em>, especially if the disease was associated with damage to the central nervous system.<\/p>\n<h2>What is the prognosis for HLH?<\/h2>\n<p>The prognosis depends on the type of HLH and how quickly treatment is started.<\/p>\n<ul>\n<li><strong>Primary HLH<\/strong>, without bone marrow transplantation, is almost always fatal. With transplantation, five-year survival rates can exceed <strong>60\u201370%.<\/strong><\/li>\n<li><strong>Secondary HLH<\/strong> has a better prognosis if the underlying cause is quickly addressed and treatment begins promptly.<\/li>\n<\/ul>\n<p>In adults, <strong>secondary HLH often has a more severe course<\/strong> because it develops on the background of pre-existing conditions. In children, outcomes are better with early diagnosis and modern treatment protocols.<\/p>\n<figure id=\"attachment_16110\" aria-describedby=\"caption-attachment-16110\" style=\"width: 770px\" class=\"wp-caption aligncenter\"><img decoding=\"async\" class=\"wp-image-16110 size-full\" src=\"https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-sora-shimaza.jpg\" alt=\"A girl is holding her stomach\" width=\"770\" height=\"350\" srcset=\"https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-sora-shimaza.jpg 770w, https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-sora-shimaza-300x136.jpg 300w, https:\/\/staging-introlab.dev-digitaldot.com\/wp-content\/uploads\/2025\/08\/pexels-sora-shimaza-768x349.jpg 768w\" sizes=\"(max-width: 770px) 100vw, 770px\" \/><figcaption id=\"caption-attachment-16110\" class=\"wp-caption-text\">HLH can lead to serious complications.<\/figcaption><\/figure>\n<h2>Frequently asked questions about HLH<\/h2>\n<h3>Can HLH come back after treatment?<\/h3>\n<p>Yes, HLH can return, especially in the primary form. In secondary HLH, the risk of recurrence depends on whether the underlying cause has been completely eliminated.<\/p>\n<h3>How does HLH affect the nervous system?<\/h3>\n<p>If it involves the brain and spinal cord, HLH can cause seizures, behavioral changes, vision problems, speech or coordination difficulties, and even loss of consciousness.<\/p>\n<h3>Can HLH be passed from person to person?<\/h3>\n<p>No, HLH is not a contagious disease. Primary HLH is inherited, and secondary HLH develops due to other health conditions or infections, but the disease itself is not directly transmitted.<\/p>\n<h3>How quickly does HLH progress?<\/h3>\n<p>In many cases, the disease can progress over several weeks, and sometimes within just a few days. The speed depends on the cause and the patient\u2019s overall health.<\/p>\n<h3>What lifestyle changes can help manage HLH?<\/h3>\n<p>A healthy diet, adequate fluid intake, light physical activity with a doctor\u2019s approval, and sufficient rest can support recovery and strengthen the body.<\/p>\n<h2>Early recognition of HLH can save lives<\/h2>\n<p>Hemophagocytic lymphohistiocytosis is a rare but extremely serious disease that requires prompt recognition and specialized treatment. <em>Because its symptoms are similar to those of other conditions, HLH is often diagnosed late.<\/em> Physician education, rapid diagnostics, and access to modern therapies are key factors that can save the lives of those affected. Timely laboratory testing plays an important role in early detection, and <a href=\"https:\/\/staging-introlab.dev-digitaldot.com\/en\/\">IntroLab in Belgrade<\/a> provides reliable analyses that can help doctors make an accurate diagnosis and determine the next steps in treatment.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>HLH is a rare disease that affects between one in 20,000 and one in 60,000 newborns each year, and it is estimated that around 250 people in Serbia live with this diagnosis. Hemophagocytic lymphohistiocytosis (HLH) is a condition in which the immune system loses its ability to precisely regulate its defensive responses. In a healthy [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":16108,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":""},"categories":[159],"tags":[],"class_list":["post-16143","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-uncategorized"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.1.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Hemophagocytic lymphohistiocytosis \u2013 Rare but serious immune disorder | Blog | IntroLab Belgrade<\/title>\n<meta name=\"description\" content=\"Hemophagocytic lymphohistiocytosis (HLH) is a rare but serious immune system disorder. 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