Cutaneous Manifestations of Internal Disease

Some cutaneous signs are specific enough to warrant a search for occult malignancy.

Acquired cutaneous paraneoplastic syndromes involve cutaneous findings associated with or related to internal malignancy.

This chapter will discuss pruritus, dermatomyositis, Sweet's syndrome, carcinoid syndrome, glucagonoma syndrome, paraneoplastic pemphigus, and the sign of Leser–Trélat.

Pruritus is a common symptom of many inflammatory dermatoses.

In the absence of skin findings, generalized pruritus may indicate occult malignancy.

Pruritus that is associated with an unknown internal malignancy is more common in gastrointestinal and lymphoproliferative malignancies.

Pruritus or itching can be nonspecific and may not be associated with obvious primary skin changes.

Patients may rub or scratch unknowingly while sleeping and during the examination.

Scratching may lead to linear edematous changes, hive-like lesions, excoriations, or lichenified or thickened skin.

Focal areas of hemorrhage or bleeding may be noted.

Some patients may have generalized scale and xerosis, without other inflammatory changes.

Pruritus associated with gastrointestinal symptoms, lethargy, weight loss, night sweats, or anemia may alert one to look for malignancy-associated pruritus.

Serologic evaluation for liver, biliary, pancreatic, and renal disease are early screening laboratory tests to obtain.

Routine complete blood count may yield clues to a systemic process or lymphoproliferative disease/bone marrow neoplasia.

The clinical course and prognosis usually depend on the associated internal malignancy.

Pruritus may be treated with topical steroids, with or without occlusion and with ultraviolet light phototherapy.

Systemic therapy with oral steroids can be prescribed but may interfere with the immune system function and malignancy treatment.

Generalized pruritus has numerous causes

Atopic dermatitis, contact dermatitis, psoriasis, scabies, renal disease, liver disease, and lymphoproliferative diseases are a few examples

All causes must be considered when assessing a patient with an unknown cause of generalized pruritus

Usually, the pruritus improves with treatment of the associated malignancy.

Antihistamines, topical steroids, emollients (Vaseline), and antipruritic lotions (Sarna) are helpful but not always curative.

Ultraviolet light phototherapy can be helpful in many patients.

Systemic therapy with oral steroids can be prescribed but may interfere with the immune system function and malignancy treatment.

Dermatomyositis is a rare skin and muscle disease that can be associated with an underlying malignancy.

Adults with dermatomyositis are more likely to have an internal malignancy than children.

The prevalence has been estimated at 5% to 50%, with the greatest prevalence among older patients.

Some malignancies are diagnosed at the time dermatomyositis is diagnosed.

The most common associated malignancies are cancers of the ovary, breast, lung, and gastrointestinal tract.

The skin findings of dermatomyositis include violaceous papules over the dorsal hand and knuckles (Gottron's papules), periungual telangiectasias, periorbital violaceous or heliotrope coloration, a photosensitive violaceous eruption of the shoulder neck and chest (shawl sign), inflamed scaly palms (mechanic's hands), and diffuse and focal areas of poikiloderma.

Dermatomyositis may be associated with proximal muscle weakness (polymyositis).

Some patients with dermatomyositis may have calcification of the muscles.

Patients with dermatomyositis with signs of internal malignancy, such fever, night sweats, weight loss, without known malignancy, should be carefully evaluated.

Skin histology shows an interface dermatitis with increased dermal mucin.

Serologic evaluation is done for Jo-1 antibodies for dermatomyositis.

If polymyositis is suspected, a muscle biopsy, electromyographic studies, and creatinine phosphokinase levels should be obtained.

It is especially important to look for ovarian and breast carcinoma in women.

The clinical course and prognosis usually depend on the associated internal malignancy.

The signs and symptoms of dermatomyositis may wax and wane, independent of the status of the malignancy, but recurrences or flares of dermatomyositis may indicate a recurrence of the malignancy.

The risk for malignancy decreases with each subsequent year after the diagnosis of dermatomyositis.

Dermatomyositis frequently is confused with lupus, eczematous dermatitis, seborrheic dermatitis, and polymorphous light eruption

Treatment of the malignancy is based on the malignancy type.

Patients with dermatomyositis should be evaluated first by screening for malignancy.

Patients with dermatomyositis should avoid intense sun exposure because this can trigger and exacerbate symptoms.

Some milder cases of dermatomyositis can be treated topically with steroids and emollients.

Dermatomyositis can be treated with systemic immunosuppressive agents, including systemic steroids, mycophenolate mofetil, cyclosporine, azathioprine, and methotrexate.

For advanced and more difficult cases, cyclophosphamide and rituximab can be prescribed.

Sweet's syndrome is also called acute febrile neutrophilic dermatosis.

It usually presents as a recurrent, sometimes painful skin eruption associated with fever, elevated white blood cell count, and arthralgias.

Women are affected more often than men.

Sweet's syndrome may be associated with acute infection or with lymphoproliferative malignancy.

Acute myelogenous leukemia is the most common associated malignancy.

The lesions of Sweet's syndrome are red, edematous, pseudovesicular, coalescing papules and plaques.

Lesions vary from 0.5 to 5.0 cm and can be tender on palpation, asymptomatic, or painful.

Sweet's syndrome lesions are frequently located on the face and dorsal hands, localized or generalized.

Sweet's syndrome may be associated with an acute infection, in which case there is usually a prodrome of fever and myalgia.

A generalized nonspecific arthritis can be associated with the syndrome.

Histology shows abundant neutrophils in the dermis without vasculitis.

The clinical course and prognosis usually depend on the associated internal malignancy.

Malignancy may follow the onset of Sweet's syndrome by 3 months.

In uncomplicated Sweet's syndrome, lesions tend to resolve in 2 to 3 weeks.

Sweet's syndrome can mimic pyoderma gangrenosum, erythema multiforme, bite reactions, lupus, and infections

Sweet's syndrome responds quickly to systemic steroids, but recurrences are common.

Malignancy and infection should be ruled out before starting steroids.

Carcinoid syndrome is an episodic, intense flushing of the face, neck, and upper body.

It is caused by a neuroendocrine tumor that releases vasoactive mediators (such as serotonin) into the systemic circulation.

Most carcinoid tumors arise in the small bowel, usually the appendix.

Usually, vasoactive mediators released from these tumors are inactivated in the liver before reaching the systemic circulation.

When carcinoid tumors metastasize to the liver, mediators have access to the systemic circulation.

Carcinoid tumors may also arise in the lung and, as such, release mediators into the systemic circulation.

Carcinoid syndrome presents as acute warmth and flushing of the upper body, especially the face, neck, and chest.

Flushing episodes last for about 30 minutes and are often associated with dyspnea, abdominal cramping, and diarrhea.

Most carcinoid tumors arise in the small bowel, usually the appendix.

Usually, vasoactive mediators released from these tumors are inactivated in the liver before reaching the systemic circulation.

When carcinoid tumors metastasize to the liver, mediators have access to the systemic circulation.

Carcinoid tumors may also arise in the lung (bronchial) and, as such, release mediators into the systemic circulation.

Increased levels of urinary 5-hydroxyindoleacetic acid after 24-hour collection and serotonin elevation in the blood.

Patients with cutaneous findings suggestive of internal carcinoid malignancy should be carefully evaluated.

Radiographic testing with computed tomography (CT) or magnetic resonance imaging (MRI) can be used to follow progression of these tumors.

The clinical course and prognosis usually depend on the size and location of the carcinoid malignancy.

Carcinoid syndrome can be confused with rosacea, contact allergy, erysipelas, cellulitis, and pellagra

Treatment is based on the size and location of the carcinoid malignancy at presentation.

There are not many medical options for treatment of carcinoid tumors, nor prevention for the flushing episodes.

Surgery is the only effective option for cure, but this is often difficult to achieve.

A rare, clinically distinctive syndrome consisting of a dynamic generalized cutaneous eruption, necrolytic migratory erythema, associated with a glucagon-secreting tumor of pancreatic alpha cells.

Necrolytic migratory erythema describes the eruption of the glucagonoma syndrome.

It is generalized but favors the flexural areas of the groin, buttocks, and thighs.

Bright dermal polycyclic patches of erythema evolve into flaccid bullae and desquamate, leaving denuded areas and a collarette of scale.

The process is dynamic, evolving, and extending each day.

Glucagonoma syndrome is associated with a tumor of the pancreatic alpha cells.

Insulin resistance and diabetes mellitus result from increased glucose levels.

Necrolytic migratory erythema histology shows a characteristic hydropic degeneration of the superficial epidermis along with intracellular edema.

The clinical course and prognosis usually depend on the associated glucagonoma.

Necrolytic migratory erythema may resemble tinea, candidiasis, eczematous dermatitis, irritant dermatitis, or acrodermatitis enteropathica

Surgical treatment of the glucagonoma tumor is required.

Octreotide has been used to inhibit the release of glucagon.

Resolution of the cutaneous changes of necrolytic migratory erythema occurs with tumor removal.

Paraneoplastic pemphigus is a painful immunologic blistering disorder of the mucosa.

It represents a sign of internal malignancy, most often lymphoproliferative in nature.

Chronic lymphocytic leukemia is the most commonly associated malignancy.

Most patients die of complications of paraneoplastic pemphigus or the underlying malignancy.

Paraneoplastic pemphigus presents as ocular inflammation, oral erosions, generalized erythema multiforme−like bullous lesions, and denuded areas of skin with crusting.

Paraneoplastic pemphigus is often associated with a lymphoproliferative or hematologic malignancy.

Chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and Castleman's disease are the most common malignant associations.

Skin biopsy shows suprabasilar acantholysis similar to pemphigus vulgaris.

Antibodies targeted to proteins on the keratinocytes and at the dermoepidermal junction can be found in the skin (direct immunofluorescence) and serum (indirect immunofluorescence).

Serum antibodies directed against desmoglien 1 and 3, desmoplakin, envoplakin, and periplakin.

The clinical course and prognosis usually depend on the associated internal malignancy.