Paraneoplastic acrokeratosis

Overview

Paraneoplastic acrokeratosis, also known as Bazex syndrome, is a rare paraneoplastic dermatosis primarily affecting middle-aged to older adults. It is most commonly associated with squamous cell carcinomas of the upper aerodigestive tract, such as cancers of the larynx, pharynx, or esophagus. The condition presents with psoriasiform skin lesions that typically begin on the acral (extremity) areas, including the hands, feet, ears, and nose, and may later extend to other body parts. Recognizing the cutaneous manifestations of paraneoplastic acrokeratosis is crucial, as they often precede the diagnosis of the underlying malignancy and serve as an early clinical marker of cancer.

Causes

Paraneoplastic acrokeratosis is not caused by a primary skin disorder but arises as a result of an internal malignancy, making it a paraneoplastic syndrome. The exact mechanism is not completely understood, but several theories have been proposed:

• Immune-mediated response: The immune system may produce antibodies or cytokines in response to the tumor, which cross-react with skin antigens, causing inflammation and keratinocyte dysfunction.

• Tumor-derived factors: Tumors may secrete growth factors or cytokines that stimulate abnormal skin cell proliferation or alter skin barrier function.

• Genetic predisposition: Some individuals may have a genetic susceptibility to developing cutaneous paraneoplastic manifestations.

The syndrome is most often associated with cancers of the upper respiratory or digestive tract, but other neoplasms such as lung, prostate, and gastrointestinal cancers have also been implicated.

Symptoms

Paraneoplastic acrokeratosis is characterized by distinctive and progressive skin changes, particularly involving acral areas. Common clinical features include:

Cutaneous Manifestations

• Symmetrical psoriasiform plaques: Red to violaceous scaly plaques that resemble psoriasis, typically on the hands, fingers, feet, ears, and nose.

• Nail abnormalities: Nail dystrophy including onycholysis (separation of nail from nail bed), thickening, ridging, and discoloration.

• Hyperkeratosis: Thickening of the skin on the palms and soles (palmoplantar keratoderma).

• Eczematous or ichthyosiform scaling: In advanced stages, lesions may resemble eczema or ichthyosis (dry, scaly skin).

• Pruritus or pain: Some patients experience itching, tenderness, or burning sensations in affected areas.

Systemic Associations

• Weight loss, fatigue, or anemia: Systemic symptoms may be present depending on the underlying cancer.

• Hoarseness, dysphagia, or persistent cough: Symptoms suggestive of head and neck tumors.

Importantly, the skin findings in Bazex syndrome often precede the diagnosis of cancer by several weeks to months, making them valuable early diagnostic clues.

Diagnosis

Diagnosis of paraneoplastic acrokeratosis is clinical, supported by histopathology and cancer screening. Key steps include:

• Clinical examination: Recognition of the characteristic acral and symmetrical psoriasiform lesions, particularly in older individuals with no history of psoriasis.

• Skin biopsy: Histological features are non-specific but may show hyperkeratosis, parakeratosis, acanthosis, and perivascular lymphocytic infiltrate, similar to psoriasis.

• Cancer screening:

  • Imaging: CT scan or PET-CT of the head, neck, and chest to search for hidden malignancies.

  • Endoscopy: May be needed for visualizing tumors in the upper aerodigestive tract.

  • Laboratory tests: Complete blood count, liver and renal function tests, and tumor markers may be ordered depending on suspected malignancy.

Diagnosis is confirmed when characteristic skin changes occur alongside a confirmed malignancy, especially if the skin lesions improve with treatment of the cancer.

Treatment

The primary treatment for paraneoplastic acrokeratosis is directed at the underlying malignancy. Management includes:

• Cancer therapy: Surgical removal, radiation, and/or chemotherapy to treat the primary tumor typically results in improvement or resolution of skin lesions.

• Topical treatments:

  • Corticosteroids: Help reduce inflammation and scaling.

  • Emollients and keratolytics: Used to soften and remove thickened skin.

• Systemic treatments: In refractory cases, systemic retinoids or immunosuppressants like methotrexate may be considered to control skin symptoms.

• Symptomatic care: Antihistamines for itching, pain relievers, and psychosocial support.

Dermatologic treatments alone are generally insufficient without addressing the underlying cancer.

Prognosis

The prognosis of paraneoplastic acrokeratosis is directly tied to the prognosis of the associated malignancy. In many cases, skin symptoms improve or resolve completely after successful treatment of the tumor. Recurrence of skin lesions may signal cancer relapse or metastasis, serving as a useful clinical marker. Early recognition of Bazex syndrome can lead to earlier cancer detection, which may improve survival outcomes. However, in cases where the underlying malignancy is advanced or untreatable, the overall prognosis is poor. Regular follow-up is essential for both cancer management and dermatologic monitoring.