Skin Changes and NETs

Neuroendocrine tumours (NETs) are a unique type of cancer that originate from neuroendocrine cells. These cells have roles in the secretion of hormones and peptides, impacting numerous body functions. One of the lesser-discussed but significant aspects of NETs is their effect on the skin. 

Cultivating a thorough understanding of the various skin changes associated with NETs is crucial for both patients and healthcare providers. These changes can provide important diagnostic clues about the disease, while directly affecting quality of life.

Neuroendocrine Cancer Australia (NECA), is dedicated to assisting individuals with neuroendocrine cancer and their families. NECA offers a wealth of resources, educational programs, and advocacy efforts aimed at deepening the understanding of NETs, improving patient care, and encouraging research advancements. Patients diagnosed with NETs can engage with NECA’s comprehensive support and information by calling the NET nurse line.

Types of skin changes in NETs

To begin a discussion about what skin changes mean for NET patients, we must first examine the types of skin changes that one could expect.

Flushing

Flushing is a common skin manifestation alongside neuroendocrine tumours, particularly those originating in the gastrointestinal tract and lungs. This symptom occurs due to the release of vasoactive substances from the tumour cells, such as serotonin and histamine. 

These substances cause blood vessels to widen (vasodilation), leading to a sudden and often intense redness or flushing of the skin. This process is exacerbated by factors like stress, alcohol, or certain foods, which can trigger the release of these substances in greater quantities.

Flushing in NETs is typically accompanied by other symptoms, including:

• Diarrhoea: Often related to the same vasoactive substances that cause flushing. This can lead to dehydration and electrolyte imbalances.
• Wheezing: This is due to bronchospasm, which can occur in conjunction with flushing. This respiratory distress can be severe in some patients.
• Heart palpitations: A result of increased cardiovascular activity induced by hormone secretion. These palpitations can cause significant anxiety and discomfort.

Telangiectasia

Telangiectasia refers to small, widened blood vessels visible near the surface of the skin. In the context of NETs, telangiectasia can develop as a direct consequence of the hormone secretion by the tumours, which can be semipermanent or permanent over time. 

This condition can make the skin appear mottled and uneven, often leading to concerns about cosmetic appearance and social stigma.

These small blood vessels often appear in various locations around the body, including:

• The face, particularly around the nose and cheeks, gives a characteristic appearance that can be distressing for patients.
• The chest and upper back, which can be visible when wearing certain types of clothing, adding to the cosmetic concerns.
• The arms, particularly the upper arms, which can be exacerbated by sun exposure and other environmental factors.

Dermatitis

Dermatitis, or inflammation of the skin, can manifest in various forms in patients with NETs:

Erythematous dermatitis is characterised by red, inflamed skin, often linked to the hormonal imbalances caused by NETs. This can be particularly itchy and uncomfortable, impacting daily activities.

Seborrheic dermatitis causes greasy, scaly patches that can appear on the scalp and face. This condition is often chronic and can fluctuate in severity, leading to periods of discomfort.The incidence of this is rare.

Common symptoms of dermatitis in NET patients include:

• Redness and swelling: Persistent inflammation due to the body’s reaction to abnormal hormone levels. This can cause significant discomfort and pain.
• Itching and discomfort: Often exacerbated by the dry, scaly nature of affected skin. Scratching can further damage the skin and increase the risk of infection.

Hyperpigmentation

Hyperpigmentation, or darkening of the skin, can occur in NET patients due to the excess production of hormones like ACTH (adrenocorticotropic hormone), which stimulates melanin production. This condition can make the skin appear blotchy and uneven, contributing to cosmetic concerns and self-esteem issues.

Hyperpigmentation often appears in patterns and in common areas such as:

• Diffuse darkening: Generalised darkening of large skin areas, which can be more noticeable in individuals with lighter skin tones.
• Localised patches: Particularly on the face, hands, and in skin folds, which can be more visible and distressing to patients.

Merkel cell Carcinoma

Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer that originates from Merkel cells, which are involved in the sense of touch. This cancer typically presents as skin changes that can be initially subtle but quickly become more pronounced.

Diagnosis of skin changes

While diagnosing skin changes associated with NETs may seem simple, the various clinical manifestations of the disease can pose problems. It’s always best to trust the opinions of your healthcare team, and follow the standard diagnostic method.

Clinical evaluation

A thorough clinical evaluation is crucial for diagnosing skin changes related to NETs. This involves:

• Detailed medical history: Including symptom onset and progression. Understanding the timeline and triggers of symptoms can help form a differential diagnosis.
• Physical examination: Focusing on skin changes and other systemic symptoms. This examination should be comprehensive and include all areas of the body, not just those presenting changes.

Dermatological examination

A specialised dermatological examination helps identify specific skin lesions and their characteristics. This may include:

• Dermatoscopy: Using a dermatoscope to magnify and better visualise skin lesions. This tool can help distinguish between benign and malignant lesions.
• Biopsy: Taking a small sample of skin tissue for histological analysis. This procedure can confirm the presence of NET cells and guide treatment decisions.

Imaging and laboratory tests

These tests can confirm NET diagnosis and understand the extent of NETs:

• Imaging tests: CT scans, Ultrasound, MRIs, and PET scans can locate and assess the primary tumour and metastases. These tests can provide detailed information about the size and location of tumours, informing the outlook of treatment.
• Laboratory tests: Including blood and urine tests to measure hormone levels and other markers indicative of NET activity. These tests can help in monitoring the disease and assessing the effectiveness of treatments.

Management of skin changes in NETs

Fortunately, some skin changes associated with NETs can be treated using a range of interventions. The specific mix of treatments will vary from patient to patient.

Medical treatments

Medications to control symptoms can play a critical role in managing the symptoms of skin changes in NETs:

• Somatostatin analogs like octreotide and lanreotide can help control hormone secretion. These medications can significantly reduce flushing and other hormone-related symptoms.
• Antihistamines can reduce flushing and itching. These drugs can provide symptomatic relief and improve the quality of life for patients.

Hormone therapy aims to reduce the production of hormones that cause skin changes:

Peptide receptor radionuclide therapy (PRRT) targets and destroys hormone-producing tumour cells. This advanced treatment can provide long-term control of hormone secretion and symptom relief.

Dermatological interventions

Topical treatments are essential for managing skin symptoms locally:

• Steroid creams: To reduce inflammation and itching in dermatitis. These creams can be effective in controlling flare-ups and providing rapid relief.
• Moisturisers: To alleviate dryness and scaling. Regular use of emollients can improve skin barrier function and reduce discomfort.

Lifestyle and supportive care

Dietary considerations

Foods and drinks containing high amounts of amines may induce or worsen symptoms related to carcinoid syndrome.

Foods and drinks moderate-to-high in amine content include: 

• Aged cheese
• Alcohol
• Smoked/salted fish and meat
• Yeast
• Fermented foods (tofu, sauerkraut)
• Caffeine (in high volumes)
• Chocolate
• Some nuts
• Coconut
• Avocado
• Banana
• Raspberries
• Soy products (soy sauce, tempeh)

Completion of a food and symptom diary should be the first step before assessing the need for dietary change, as any relationship between particular symptoms and food types is likely to be individual.

Implementing a consistent skin care regimen can greatly benefit patients with NET-related skin changes:

• Gentle cleansers: To avoid irritating sensitive skin. Using products free from harsh chemicals and fragrances can prevent exacerbation of symptoms.
• Regular moisturising: To maintain skin hydration. Keeping the skin well-moisturised can reduce itching and improve overall comfort.

Developing coping strategies is important for managing the emotional and physical impacts of skin changes:

• Stress management techniques: Such as mindfulness and meditation. These practices can help reduce the severity of symptoms triggered by stress.
• Support groups: To connect with others facing similar challenges. Sharing experiences and advice can provide emotional support and practical tips for managing symptoms.

Impact on quality of life

Skin changes can significantly impact the physical well-being of NET patients:

• Discomfort and pain: From persistent itching and inflammation. These symptoms can interfere with daily activities and reduce overall quality of life.
• Functional limitations: Due to the severity of skin conditions. Severe dermatitis or hyperpigmentation can limit mobility and affect the ability to perform routine tasks.

The emotional toll of skin changes should not be underestimated. Due to visible changes and discomfort. The chronic nature of these symptoms can lead to significant mental health issues, such as anxiety and depression. Body image issues can affect self-esteem and social interactions.

Fortunately, there is help out there. Access to support resources and patient education can drastically improve a patient’s quality of life.

• Educational materials: On managing skin symptoms and NETs. Providing patients with comprehensive information can empower them to take an active role in their care. Neuroendocrine Cancer Australia’s NET nurse line is one of the best resources for patients in Australia.
• Counselling services: For emotional and psychological support. Professional counselling can help patients cope with the mental health challenges associated with NETs. Contact our NET Nurse for appointments with a NECA Counsellor.

Research and future directions

Research is continuously advancing our understanding of skin changes in NETs. Clinical trials: are constantly exploring new treatments and interventions. Participation in clinical trials can provide access to cutting-edge therapies and contribute to scientific knowledge. Genetic studies are also in the works to identify risk factors and mechanisms. Understanding the genetic basis of NETs can lead to more targeted and effective treatments.

Future therapies hold promise for better management of skin changes in NETs. Targeted therapies are aimed at specific pathways involved in hormone production, and can provide more effective control of symptoms with fewer side effects.

Innovative dermatological treatments such as advanced laser technologies and topical agents are also showing promise. Continued research and development in dermatology can offer new options for managing skin symptoms.

Understanding the complexities of skin changes in neuroendocrine tumours is essential for comprehensive patient care. Effective management involves a combination of medical treatments, dermatological interventions, and supportive care to improve the quality of life for patients. As research continues to evolve, new therapies and insights will further enhance our ability to address these challenging symptoms.

Further information and support for people diagnosed with NETs is available by calling the NECA NET nurse line.