Introduction

Kaposi Sarcoma (KS) is a cancer of soft tissues such as skin and lymph nodes. It is highly associated with the human herpesvirus 8 (HHV-8) and patients with a suppressed immune system. Although KS occurs very rarely in children and infants, it manifests more severely compared to adult patients, especially in terms of its spread to internal organs. Symptoms can vary between cases, depending on the disease's manifestation and the method of transmission.¹

Primary cause

The cause of KS is HHV-8 infection, which is most likely transmitted in young children via the exchange of saliva and blood transfusion. It is important to note that, like HIV, it can be transmitted sexually and through shared intravenous needles. Despite HHV-8 being present in breast milk, there is currently no evidence suggesting that it can be passed from HHV-8-infected mothers to their children via breastfeeding. For KS to develop, the patient needs to be infected with HHV-8 and have a suppressed immune system to allow HHV-8 to infect cells and develop into cancer.^1,2

When a patient is infected with HHV-8, the virus infects endothelial cells in the skin and lymph nodes, causing them to transition into a mesenchymal cell type. Essentially changing their structure and function, which is a common early stage in cancer. The infection then promotes the formation of new blood vessels to supply these cells. Together with the promoted suppression of the immune system, either by HHV-8 itself or other causes, this allows these cells to divide rapidly, forming KS tumours. Due to the inflammation and increased blood supply at the site of these tumours, they appear pink to purple, which can be visible if the skin is affected.^1,3,4

Types and risk factors

There are four distinct types of KS, with each type being more prevalent in different age groups:^5,6,7

• Classic KS: usually affects men over 50, with Mediterranean and Ashkenazi Jewish origin 
• Endemic KS: common in children and males over 40 in Central and East Africa 
• Epidemic KS: also known as autoimmune deficiency syndrome-KS (AIDS-KS), usually caused by the human immunodeficiency virus (HIV), which attacks the immune system, allowing for the development of KS 
• Post-transplant KS: when a patient is given immunosuppressive treatment that leads to the reactivation of a prior HHV8 infection, or when the patient receives an organ from an infected donor. Reducing immunosuppression, when feasible, can lead to the regression of post-transplant KS

Risk factors in adults

• Males
• HIV infection
• Organ transplant recipients 
• Mediterranean and Ashkenazi ethnicity 
• Over the age of 50 years 

Risk factors in children

• HIV infection
• Endemic areas
• Weakened immune system

Clinical presentation

Adult KS symptoms

Adults usually present with several KS symptoms, and they include:^8,9

• Slow-growing pink to purple lesions on the skin
• Inflamed or enlarged lymph nodes 
• Signs of a suppressed immune system
• Recurrent or more severe infections, which can manifest as ear infections, common cold or more severe organ infections such as meningitis

Paediatric KS symptoms

When compared to adult patients with KS, the majority of the symptoms in children overlap, however, children tend to have an increased severity of symptoms and rapid disease progression. These can include:¹⁰ 

• Enlarged spleen and liver
• High inflammatory markers in the blood 
• Low platelets (thrombocytopenia)

Enlarged lymph nodes can be observed in both adults and children; however, it is more commonly observed in children, with skin lesions being a more prominent clinical feature in adult patients.¹¹

Diagnosis

Blood tests are usually the first-line tests carried out for suspected KS, which may reveal diminished white blood cells, and whether the patient is HHV-8 or HIV positive. The gold standard for diagnosis is a biopsy of the suspected lesion and analysis under the microscope. Due to the various ways in which KS can present and manifest, it may be difficult to identify, thus requiring experienced pathologists and thorough examination.¹²

Treatment approaches

Both adults and children with the epidemic KS subtype appear to respond well to combination antiretroviral therapy (cART). This form of therapy works to diminish HIV levels in the blood and restore CD4 levels, thus reversing suppression of the immune system. A more robust immune system can subsequently function normally and target the KS cells.¹²

Chemotherapy is designed to target and eliminate rapidly dividing cells, and given the aggressive nature of Kaposi's Sarcoma (KS) in children, it is generally preferred over topical treatments since it acts systemically. While children can receive different types of chemotherapy agents, some studies indicate that oral etoposide is a useful, non-invasive option that has few side effects and enhances the child’s quality of life. In addition, there has been evidence that treating AIDS-KS with both cART and chemotherapy can improve outcomes in both children and adults, through the reduced risk of mortality and remission.

Radiation therapy works in a similar way to treat the tumours and can be an alternative option to target the affected cells systemically. In milder forms of KS (typically in adults), topical therapies may include surgery for lesion removal and the use of liquid nitrogen to freeze the lesions.^13,14,15

Prognosis and outcomes

Like with most cancers, early diagnosis, treatment and intervention are important to limit the spread of the disease and tackle the root cause, in this case being immunosuppression. Due to how quickly the lesions develop in children and the aggressive manifestation, the prognosis tends to be poorer in children. The difficulty in diagnosis and limited access to medication and appropriate healthcare in endemic areas can contribute to this delay.¹⁴ 

The overall prognosis for adults is estimated to have a 70-90% survival rate within 2 to 10 years following diagnosis. Nevertheless, a connection has been established between a worse prognosis and elevated levels of C-reactive protein (CRP) (an inflammation marker) in the bloodstream, a reduced CD4 count, and metastasis to other organs, especially the lungs.^1,8

Summary

• KS is caused by both infection with the HHV-8 virus and the suppressed immune system of a patient, which can be caused by HIV and immunosuppressive medication 
• Young children usually acquire KS endemically, particularly in East and Central Africa 
• Adults usually acquire KS due to HIV or classically (affecting predominantly males of Ashkenazi and Mediterranean descent) 
• Adult symptoms are usually milder with slower progression, affecting mostly the skin and lymph nodes 
• Symptoms in children are usually more severe and have rapid progression, affecting internal organs more than in adults 
• Treatment usually aims to target the cancer cells and improve the immune system