From the Guidelines
Paraneoplastic processes that cause skin changes include acanthosis nigricans, dermatomyositis, erythema gyratum repens, necrolytic migratory erythema, Sweet's syndrome, and paraneoplastic pemphigus, as well as cutaneous toxicities associated with immune checkpoint inhibitor therapy, such as rash, pruritis, and vitiligo 1.
Key Paraneoplastic Processes
- Acanthosis nigricans: presents as velvety, hyperpigmented plaques in body folds and is associated with gastrointestinal malignancies
- Dermatomyositis: causes a heliotrope rash on the eyelids and Gottron's papules on knuckles, linked to ovarian, lung, and pancreatic cancers
- Erythema gyratum repens: shows concentric, wood-grain-like erythematous rings and relates to lung cancer
- Necrolytic migratory erythema: presents as erythematous patches with central blistering and is associated with glucagonoma
- Sweet's syndrome: manifests as painful, erythematous plaques and is linked to hematologic malignancies
- Paraneoplastic pemphigus: causes painful oral erosions and polymorphous skin lesions, commonly associated with lymphoproliferative disorders
Cutaneous Toxicities Associated with Immune Checkpoint Inhibitor Therapy
- Rash: often the earliest observed immune-related adverse event (irAE), typically noted within 3 weeks after the initiation of ipilimumab and within 6 weeks following the start of anti–PD-1 therapy 1
- Pruritis: can be severe and is the most common associated symptom
- Vitiligo: presents as well-demarcated depigmented macules and patches, reported primarily in patients with melanoma
Importance of Early Recognition
Early recognition of these distinctive skin changes can lead to earlier cancer diagnosis and improved outcomes, as well as timely management of cutaneous toxicities associated with immune checkpoint inhibitor therapy, which is crucial to enhance compliance, treatment continuation, and ultimately therapeutic efficacy 1.
Management of Cutaneous Toxicities
Once identified, cutaneous toxicities should be managed according to guidelines using an interprofessional approach through early engagement of a dermatologist to guide evidence-based specialty care, with the goal of safe and timely return to treatment 1.
From the Research
Paraneoplastic Skin Changes
The following paraneoplastic processes can cause skin changes:
- Cutaneous metastases
- Tripe palms
- Sweet's syndrome
- Glucagonoma
- Paget's disease and extramammary Paget's disease
- Acanthosis nigricans
- Birt-Hogg-Dube syndrome
- Basal cell nevus syndrome
- Bazex syndrome (acrokeratosis paraneoplastica)
- Carcinoid syndrome
- Cowden's disease (multiple hamartoma syndrome)
- Dermatomyositis
- Erythema gyratum repens
- Ichthyosis acquisita
- Von Recklinghausen's disease
- Pityriasis rotunda
- Pyoderma gangrenosum
- Quincke's edema (angioedema and paraneoplastic uricaria)
- Paraneoplastic pemphigus
- Degos' disease
- Superior vena cava syndrome
- Werner's syndrome
- Diffuse normolipemic plane xanthomas
- Yellow nail syndrome 2
Specific Paraneoplastic Dermatoses
Some specific paraneoplastic dermatoses include:
- Malignant acanthosis nigricans, characterized by velvety, verrucous, hyperpigmented plaques that usually affect intertriginous areas
- Necrolytic migratory erythema, which can be misdiagnosed due to its similarity to seborrheic dermatitis
- Paraneoplastic autoimmune multiorgan syndrome (PAMS), a paradigmatic form of obligate paraneoplastic dermatosis
- Paraneoplastic dermatomyositis, a facultative paraneoplastic dermatosis that can be associated with neoplasia in a variable percentage of cases 3
Common Paraneoplastic Skin Changes
Common paraneoplastic skin changes associated with internal malignancies include:
- Acanthosis nigricans
- Dermatomyositis
- Secondary ichthyosis
- Glucagonoma syndrome, consisting of alpha cell tumor of the pancreas, migratory necrolytic erythema, and diabetes mellitus 4
Life-Threatening Paraneoplastic Cutaneous Syndromes
Life-threatening paraneoplastic cutaneous syndromes include:
- Acanthosis nigricans
- Acrokeratosis paraneoplastica of Bazex
- Dermatomyositis
- Erythema gyratum repens
- Necrolytic migratory erythema (glucagonoma syndrome)
- Paraneoplastic pemphigus 5
Paraneoplastic Skin Diseases
Paraneoplastic skin diseases can be assigned according to the triggering type of malignancy, including:
- Digestive tract malignancies: acanthosis nigricans, florid cutaneous papillomatosis, necrolytic migratory erythema, Leser-Trélat syndrome, palmoplantar keratoderma, panniculitis, and pityriasis rubra pilaris
- Hematolymphoid malignoma: acquired ichthyosis, exfoliative erythroderma, necrobiotic xanthogranuloma, paraneoplastic pemphigus, plane xanthoma, pyoderma gangrenosum, scleromyxedema, Sweet syndrome, and leukocytoclastic vasculitis
- Other malignancies: Trousseau's syndrome, dermatomyositis, erythema gyratum repens, hypertrichosis lanuginosa acquisita, and papuloerythroderma of Ofuji 6