Kaposi Sarcoma: Symptoms, Types, Causes and Treatment

Kaposi sarcoma (KS) is a unique and complex disease that bridges the worlds of infectious disease, oncology, and immunology. Once a medical curiosity, KS became widely recognized as an AIDS-defining illness. Today, it remains a significant health concern—not only for people living with HIV/AIDS but also for organ transplant recipients, individuals from certain geographic regions, and the elderly. This article provides a comprehensive overview of the symptoms, types, causes, and treatments of Kaposi sarcoma, designed to inform patients, caregivers, and curious readers alike.

Symptoms of Kaposi Sarcoma

Recognizing the symptoms of Kaposi sarcoma is crucial for early diagnosis and effective management. The disease manifests in a variety of ways, depending on the affected organs and the underlying type of KS. Symptoms can range from subtle skin changes to serious systemic illness.

Symptom	Manifestation	Frequency/Severity	Sources
Skin Lesions	Purple, red, or brown patches, plaques, or nodules (often on legs, face, feet)	Most common, can be indolent or aggressive	6 7 9 10 14
Mucosal Lesions	Lesions in mouth, nose, throat	Common in HIV-related KS	9 10 14
Edema	Swelling in limbs or face	Often due to lymphatic involvement	1 3 9
GI Symptoms	Abdominal pain, bleeding, urgent symptoms	Less common, sometimes only manifestation	3 4 9
Respiratory	Cough, dyspnea, hemoptysis, stridor	Can be severe in pulmonary KS	2 5 9
Systemic	Fever, weight loss, anemia, shock	Seen in advanced cases or KICS	1 3 5

Table 1: Key Symptoms of Kaposi Sarcoma

Skin and Mucosal Lesions

Skin involvement is the hallmark of KS. Lesions may appear as flat patches, raised plaques, or nodules, often with a purple, red, or brown hue. They're most commonly found on the lower legs, feet, or face, but any skin area may be affected. In some forms, particularly HIV-associated KS, lesions can also occur in the mouth, nose, or throat, making eating and speaking difficult 6 7 9 10 14.

Edema (Swelling)

Many patients develop swelling, often in the legs or face. This occurs when KS infiltrates the lymphatic system, obstructing lymphatic drainage. The swelling can be mild or severe, sometimes leading to "woody" thickening of the skin and underlying tissues 1 3 9.

Gastrointestinal and Abdominal Symptoms

KS can involve the gastrointestinal tract, leading to symptoms such as abdominal pain, urgent bowel symptoms, or even gastrointestinal bleeding. Sometimes, the only sign of KS may be internal, making diagnosis challenging 3 4 9.

Respiratory Symptoms

When KS affects the lungs, symptoms may include cough, shortness of breath (dyspnea), coughing up blood (hemoptysis), or airway obstruction (stridor). Such involvement can be life-threatening, especially in immunocompromised patients. Pulmonary function tests and imaging may be required for diagnosis 2 5 9.

Systemic Symptoms

In advanced or aggressive KS, particularly when complicated by KSHV Inflammatory Cytokine Syndrome (KICS), patients may experience fever, profound anemia, low albumin, shock, and multiorgan failure. These systemic symptoms can mimic infectious or autoimmune diseases, making diagnosis more complex 1 3 5.

Types of Kaposi Sarcoma

Kaposi sarcoma is not a single disease but a family of related conditions, each with its own epidemiology, risk factors, and clinical course. Understanding the types of KS is essential for accurate diagnosis and tailored treatment.

Type	Typical Patient/Setting	Key Features	Sources
Classic	Elderly men, Mediterranean/Eastern European	Indolent skin lesions, lower legs, slow progression	6 7 8 9 14 18
Endemic (African)	Children and adults, sub-Saharan Africa	Aggressive, lymphadenopathy, skin & visceral involvement	3 7 9 14 18
Iatrogenic	Organ transplant recipients	May regress if immunosuppression reduced, can be aggressive	6 9 10 14 18
Epidemic (AIDS-related)	HIV-infected individuals	Rapid, widespread, affects skin, mucosa, viscera	6 7 9 10 14 18

Table 2: Main Types of Kaposi Sarcoma

Classic Kaposi Sarcoma

• Who is affected? Primarily elderly men of Mediterranean or Eastern European descent.
• Presentation: Slow-growing, pigmented skin lesions, often on the legs. Typically indolent; visceral involvement is rare. Patients may live many years with stable disease 6 7 8 9 14.
• Progression: Gradual and chronic; often not life-threatening.

Endemic (African) Kaposi Sarcoma

• Who is affected? Children and adults in sub-Saharan Africa.
• Presentation: Can be aggressive, with symmetric lymphadenopathy, oral or GI lesions, and sometimes respiratory symptoms. Both skin and visceral organs may be affected 3 7 9 14 18.
• Progression: Variable—can be indolent or rapidly progressive, particularly in children.

Iatrogenic (Transplant-Associated) Kaposi Sarcoma

• Who is affected? Organ transplant recipients (kidney, liver, heart), due to immunosuppressive therapy.
• Presentation: Skin and/or visceral lesions; may be less aggressive than AIDS-KS. Lesions may regress if immunosuppression is reduced or stopped 6 9 10 14 18.
• Progression: Can be managed by adjusting immunosuppression, but risk of graft rejection must be balanced.

Epidemic (AIDS-Related) Kaposi Sarcoma

• Who is affected? People with HIV/AIDS, especially those with low CD4 counts or uncontrolled infection.
• Presentation: Rapidly progressive and widespread. Involves skin, mucosa, lymph nodes, GI tract, lungs, and other organs 6 7 9 10 14 18.
• Progression: Often aggressive; can be life-threatening if untreated.

Causes of Kaposi Sarcoma

Kaposi sarcoma stands out as a cancer with an infectious origin. Its development is closely linked to a specific virus and influenced by the host's immune status and other cofactors.

Cause	Role in KS Development	Populations Most Affected	Sources
KSHV/HHV-8	Essential viral cause	All KS types	11 12 13 14 15
Immunosuppression	Facilitates KS development	HIV/AIDS, transplant patients	6 9 12 14 15
Genetic Factors	Possible susceptibility	Certain ethnic groups	6 9
Cytokine Dysregulation	Promotes lesion growth	Advanced cases, KICS	1 5 11 15

Table 3: Major Causes and Risk Factors for Kaposi Sarcoma

Kaposi Sarcoma-Associated Herpesvirus (KSHV/HHV-8)

• Universal cause: All forms of KS are caused by infection with Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). Detection of KSHV DNA in virtually all KS lesions confirms this link 11 12 13 14 15.
• Transmission: KSHV is primarily spread via saliva, but blood and sexual transmission can also occur, especially in high-prevalence populations 14.
• Mechanism: The virus produces proteins that drive cell proliferation, suppress apoptosis, and promote the formation of new blood vessels (angiogenesis), all hallmark features of KS lesions 11 12 13 15.

Immunosuppression

• HIV/AIDS: Profound immunosuppression in HIV-infected individuals facilitates the development and spread of KSHV, leading to epidemic KS 6 9 12 14 15.
• Transplantation: Organ transplant recipients are at high risk due to chronic immunosuppressive therapy, which lowers the immune system's ability to control latent KSHV infection 9 12 14.
• Other causes: Rarely, immunosenescence (aging-related immune decline) in elderly individuals can predispose to classic KS 6 9.

Genetic Susceptibility

• Certain ethnic groups (Mediterranean, Jewish, African) have a higher prevalence of KS, possibly due to genetic or environmental factors that affect immune response or viral transmission 6 9.

Cytokine Dysregulation and Inflammatory Response

• Chronic immune activation and dysregulated production of cytokines such as interleukin-6 (IL-6) and IL-10 can fuel KS lesion growth. This is particularly evident in KSHV Inflammatory Cytokine Syndrome (KICS), a complication marked by severe systemic inflammation 1 5 11 15.

Treatment of Kaposi Sarcoma

Treatment for Kaposi sarcoma varies depending on the type, extent of disease, immune status, and patient preferences. Advances in antiretroviral therapy and oncology have dramatically improved outcomes for many patients, but challenges remain—especially in resource-limited settings.

Treatment Approach	Indication/Setting	Notes/Effectiveness	Sources
Antiretroviral Therapy	HIV-associated KS	Often leads to KS regression	14 17 18 19
Local Therapies	Limited skin/mucosal disease	Surgery, radiation, topical agents	16 18
Systemic Chemotherapy	Advanced or visceral KS	PLD and paclitaxel are first-line	16 18 19
Immunotherapy	Selected cases (e.g., interferon)	Sometimes used in classic KS	16 18 19
Reduce Immunosuppression	Iatrogenic KS (transplant)	May cause regression but risk graft loss	9 14 18
Novel/Targeted Therapies	Refractory or advanced cases	Antiangiogenic agents, mTOR inhibitors	14 18 19

Table 4: Main Treatment Options for Kaposi Sarcoma

Antiretroviral Therapy (ART)

• First-line for HIV-associated KS: Suppression of HIV with ART often leads to immune recovery and regression of KS lesions. In some cases, ART alone is sufficient; systemic therapy is reserved for extensive disease 14 17 18 19.
• KS-IRIS: Immune reconstitution after ART initiation can sometimes paradoxically worsen KS (immune reconstitution inflammatory syndrome, or KS-IRIS), which may require additional intervention 5 18.

Localized Therapies

• Radiation therapy: Highly effective for localized skin lesions, with response rates up to 93% 16 18.
• Surgical excision: Selected for solitary or small lesions.
• Intralesional chemotherapy: Agents such as vincristine or interferon can be injected directly into lesions 16 18.
• Topical treatments: Imiquimod and retinoids may be used for superficial lesions 16 18.

Systemic Chemotherapy

• Indications: For patients with extensive, rapidly progressive, or visceral disease.
• Preferred agents: Pegylated liposomal doxorubicin (PLD) and paclitaxel are standard first- and second-line therapies, with high response rates 16 18 19.
• Other options: Vinblastine, vincristine, etoposide, and bleomycin, alone or in combination 16 18 19.

Immunotherapy

• Interferon-alpha: Used in some cases of classic or HIV-associated KS, particularly where immune function is relatively preserved 16 18 19.

Management of Iatrogenic (Transplant-Related) KS

• Reducing immunosuppression: Often results in regression of lesions. However, this must be balanced against the risk of organ rejection 9 14 18.
• Switching agents: mTOR inhibitors may be considered as they have both immunosuppressive and antitumor effects 18.

Emerging and Targeted Therapies

• Antiangiogenic agents: New drugs targeting blood vessel formation are under investigation and show promise in refractory cases 19.
• KSHV-targeted therapies: As the role of the virus becomes clearer, treatments directly targeting KSHV or its pathways are being developed 14 19.

Conclusion

Kaposi sarcoma is a multifaceted disease at the intersection of cancer and infectious disease. Understanding its symptoms, types, causes, and treatment options is vital for timely diagnosis and optimal management. Here’s a summary of the main points:

• Symptoms: Range from skin and mucosal lesions to systemic illness, depending on KS type and severity.
• Types: Four main types—classic, endemic, iatrogenic, and epidemic (AIDS-related)—each with distinct features and at-risk populations.
• Causes: All KS is caused by KSHV/HHV-8 infection, with immunosuppression and cytokine dysregulation playing key roles.
• Treatment: Depends on KS type and extent; options include ART, local therapies, systemic chemotherapy, immunotherapy, and reduction of immunosuppression for transplant recipients. New, targeted treatments are on the horizon.

Kaposi sarcoma remains a challenge—especially in resource-limited parts of the world—but advances in understanding and therapy continue to bring hope for better outcomes. Early recognition and individualized treatment can make a substantial difference in the lives of those affected.