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PubMed This is a summary of 9 peer-reviewed journal articles Updated
Immunology

Symptoms and Warning Signs

At a Glance

STK4 deficiency commonly causes recurrent respiratory infections, persistent warts or molluscum, eczema, and autoimmune blood-cell problems. Because lymphoma risk is increased, fever, breathing trouble, growing lumps, night sweats, weight loss, or severe illness need prompt medical attention.

Because STK4 deficiency is a combined immunodeficiency, it affects many different parts of the body at once. While every patient’s journey is different, researchers have identified a common pattern of symptoms that usually begin in early childhood, though adult-onset has been reported [1][2].

Understanding what is “expected” versus what is an “emergency” can help you manage day-to-day care while staying alert for more serious complications. The statistics discussed below come from a small, referral-based 2021 cohort of 24 published patients and represent reported cases, not an individual’s precise prognosis [1].

Common Respiratory and Skin Infections

Most patients with STK4 deficiency will deal with frequent infections. In the 24-patient published cohort, 18 experienced recurrent pneumonia (lung infections), and 20 had chronic skin viral infections [1].

  • Bacterial Infections: Recurrent pneumonia, ear infections, and sinus infections are common because the body struggles to clear bacteria effectively [1][3].
  • Viral Skin Infections: You may see extensive or persistent warts or molluscum contagiosum (small, pearl-like bumps). These can be frustrating and difficult to treat [1][4].
  • Atopic Dermatitis: Roughly 40% of patients in the reported cohort developed atopic dermatitis (eczema), which causes itchy, red, or inflamed skin [1][5].

Immune Dysregulation and Autoimmunity

Sometimes, the immune system in STK4 deficiency doesn’t just under-react to germs; it becomes dysregulated and attacks the body’s own healthy cells. This is called autoimmunity [1].

  • Autoimmune Cytopenias: This occurs when the immune system destroys its own blood cells. It can lead to low red blood cells (anemia), which causes paleness and fatigue, or low platelets (thrombocytopenia), which leads to easy bruising or tiny red spots on the skin called petechiae [1][6].
  • Organ Enlargement: You or your doctor may notice lymphadenopathy (swollen lymph nodes), hepatomegaly (enlarged liver), or splenomegaly (enlarged spleen). This often happens because the body is trying to manage a chronic infection like the Epstein-Barr virus (EBV) or because immune cells are accumulating in these organs [1][6].

Understanding the Risk of Lymphoma

One of the most serious complications of STK4 deficiency is an increased risk of lymphoma (a cancer of the immune system). In the small reported cohort, 6 out of 24 patients (25%) developed some form of lymphoma [1].

Many of these cases are linked to EBV, a common virus that the immunocompromised body cannot keep in check, allowing it to drive the overgrowth of certain immune cells [1][7]. However, it is important to know that lymphoma can also occur in these patients even if they do not have a detectable EBV infection [6]. This means that regular monitoring by an oncology and immunology team is vital regardless of viral test results.

When to Seek Urgent Medical Care

Fever in a person with a combined immunodeficiency requires immediate attention. You should have a clinician-defined fever and respiratory action plan (with a 24-hour contact number and temperature thresholds) provided by your immunologist. In many immunocompromised patients, any measured fever warrants same-day clinician contact.

Red Flags: Seek Immediate Care

If any of the following occur, contact your medical team or seek emergency care immediately as directed by your action plan:

  • Fever: Any fever that meets your specialist’s threshold for action, or is accompanied by chills or lethargy [1].
  • Severe Respiratory Distress: Grunting, nostrils flaring, the skin pulling in around the ribs with every breath (retractions), or bluish lips/skin (cyanosis) [1].
  • Airway Emergency: Sudden facial or tongue swelling, or difficulty breathing and swallowing [8].
  • Rapidly Enlarging Lumps: Any lymph node or bump (in the neck, armpits, or groin) that grows quickly or feels hard and fixed in place [7][6].
  • Unexplained B-Symptoms: Drenching night sweats that require a change of clothes, or unintentional weight loss [9].
  • Severe Neurological Changes: Intractable, severe headaches or a sudden new neurologic deficit [8].
  • Signs of Sepsis: Extreme lethargy (difficulty waking up), cool or mottled skin, or a significantly decreased amount of urine [1].
  • Significant Bleeding: Unexplained heavy bruising or bleeding from the gums or nose that does not stop [1][6].

Common questions in this guide

What symptoms are common in STK4 deficiency?
Common problems include repeated pneumonia, ear or sinus infections, persistent warts or molluscum contagiosum, and eczema. Some people also develop autoimmune blood-cell problems, swollen lymph nodes, or an enlarged liver or spleen.
When should a person with STK4 deficiency seek urgent care for a fever?
Follow the fever threshold and contact instructions provided by your immunologist; many immunocompromised people need same-day medical advice for any measured fever. Fever with chills, unusual sleepiness, breathing difficulty, blue lips, or other signs of severe illness requires urgent or emergency care according to the action plan.
Does STK4 deficiency increase the risk of lymphoma?
Yes. Published reports include lymphoma in 6 of 24 patients, but this small, referral-based group cannot predict an individual's risk. Lymphoma is often associated with Epstein-Barr virus, although it can occur even when EBV is not detected, so ongoing immunology and oncology monitoring is important.
What changes could be warning signs of lymphoma or another serious complication?
Report a lymph node or lump that grows quickly or feels hard and fixed, drenching night sweats, or unexplained weight loss promptly. These findings can have causes other than lymphoma, but they need timely assessment in someone with STK4 deficiency.
Why can STK4 deficiency cause bruising, pale skin, or fatigue?
Immune dysregulation can cause the body to destroy its own blood cells. Low red blood cells can cause paleness and fatigue, while low platelets can cause easy bruising, tiny red skin spots, or bleeding.
Are persistent warts or eczema more than a skin problem in STK4 deficiency?
They can reflect difficulty controlling viral skin infections or immune dysregulation, rather than being only cosmetic concerns. Persistent or treatment-resistant warts, molluscum, or eczema should be discussed with the immunology team.

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References

References (9)
  1. 1

    Diversity in Serine/Threonine Protein Kinase-4 Deficiency and Review of the Literature.

    Cagdas D, Halacli SO, Tan C, et al.

    The journal of allergy and clinical immunology. In practice 2021; (9(10)):3752-3766.e4 doi:10.1016/j.jaip.2021.05.032.

    PMID: 34146746
  2. 2

    Epidermodysplasia Verruciformis and Vδ2 γδ T-cell Expansion in STK4 Deficiency.

    Ying W, Long X, Vandergriff T, et al.

    Journal of clinical immunology 2024; (44(8)):172 doi:10.1007/s10875-024-01780-z.

    PMID: 39110273
  3. 3

    A Novel STK4 Mutation Impairs T Cell Immunity Through Dysregulation of Cytokine-Induced Adhesion and Chemotaxis Genes.

    Guennoun A, Bougarn S, Khan T, et al.

    Journal of clinical immunology 2021; (41(8)):1839-1852 doi:10.1007/s10875-021-01115-2.

    PMID: 34427831
  4. 4

    A novel mutation in the STK4 gene (Serine/threonine kinase 4) in a Chinese Blang child.

    Liu Y, Lei Y, Li M, et al.

    Immunology letters 2026; (280()):107182 doi:10.1016/j.imlet.2026.107182.

    PMID: 42119789
  5. 5

    Case Report of Two Independent Moroccan Families with Syndromic Epidermodysplasia Verruciformis and STK4 Deficiency.

    El Kettani A, Ouair H, Marnissi F, et al.

    Viruses 2024; (16(9)) doi:10.3390/v16091415.

    PMID: 39339890
  6. 6

    EBV Negative Lymphoma and Autoimmune Lymphoproliferative Syndrome Like Phenotype Extend the Clinical Spectrum of Primary Immunodeficiency Caused by STK4 Deficiency.

    Schipp C, Schlütermann D, Hönscheid A, et al.

    Frontiers in immunology 2018; (9()):2400 doi:10.3389/fimmu.2018.02400.

    PMID: 30386345
  7. 7

    STK4 deficiency and EBV-associated lymphoproliferative disorders, emphasis on histomorphology, and review of literature.

    Saglam A, Cagdas D, Aydin B, et al.

    Virchows Archiv : an international journal of pathology 2022; (480(2)):393-401 doi:10.1007/s00428-021-03147-w.

    PMID: 34604912
  8. 8

    A case report of sinusoidal diffuse large B-cell lymphoma in a STK4 deficient patient.

    Ashrafi F, Klein C, Poorpooneh M, et al.

    Medicine 2020; (99(9)):e18601 doi:10.1097/MD.0000000000018601.

    PMID: 32118703
  9. 9

    Serine/Threonine Kinase 4 Deficiency Caused by a Potential Novel c.248del, p.Pro83Leufs∗3 Mutation: A Case Report.

    Ashayeri H, Eskandarzadeh S, Alavi S, et al.

    Case reports in immunology 2026; (2026()):8573882 doi:10.1155/crii/8573882.

    PMID: 42602440

This page is for informational purposes only and does not constitute medical advice. Ask your immunology team how these warning signs apply to you and follow your individualized fever and respiratory action plan.

Guide contents Combined immunodeficiency due to STK4 deficiency
Research & Literature
01 Understanding STK4 Deficiency 03 The Path to Diagnosis