What is Acrokeratosis Paraneoplastica?

Acrokeratosis paraneoplastica is also known as Bazex syndrome and is a rare paraneoplastic syndrome, a constellation of findings, which is due to the underlying presence of a systemic malignancy. It is important to take note of such conditions because a high index of suspicion is needed to make a diagnosis of the malignancy.

Clinical Features

It is a skin condition that consists of red scaly lesions over the extremities (the ears, nose, hands and feet), and is mostly associated with cancers of the upper airway or gastrointestinal tract. The lesions are present equally on both sides, and are not itchy in the majority of cases. Beginning at the very tips, they progress inwards and may finally involve the scalp, the legs or the arms, or the trunk. The patient usually gives a history of losing significant weight over the last year or so.

The typical patient is a white male who is over 40 years of age. In most cases various topical treatments are applied unsuccessfully. Treatment of the cancer often leads to partial resolution of skin symptoms as well. Early studies noted that a recurrence of the cancer was often heralded by the reappearance of previously healed skin lesions, underlining their paraneoplastic nature.

The nails are usually quickly involved, and become red and swollen, however, lacking any evidence of infection. Late involvement of the scalp may lead to a honeycomb appearance.

The skin lesions usually predate the clinical diagnosis of cancer by about 11 months on average. In about 60% of cases the cancer is a squamous cell carcinoma, of the head and neck, or the lungs. In 16% it is a poorly differentiated carcinoma, in about 8% an adenocarcinoma of the prostate, lung, stomach or esophagus, and very uncommonly it follows a small cell carcinoma of the lung, a bladder cancer, blood cancers or lymphoid malignancies, and cancers of the gall bladder, uterus or breast, among others.

Mechanism

It is not quite clear why skin lesions result from these cancers, but some think that the reaction is due to cross-reacting antibodies against the tumor, which bind to the keratinocytes or basement membrane of the skin, damaging it. Another theory is that the skin of such patients contains antigens resembling those in the tumor which stimulate the immune system. Others suggest that the tumor produces growth factors, molecules which stimulate the growth of the keratinocytes, such as transforming growth factor-1 or insulin growth factor-1, which cause the skin to become thickened and to peel.

Diagnosis and Management

The medical history should take note of risk factors for cancer such as smoking, alcohol and environmental toxins. Specific questioning will typically lead to the admission of fatigue, a feeling of not being well, and significant weight loss over the short term.

The early tests usually involve skin biopsy and direct immunofluorescence examination, which yield nonspecific results. If the lesions persist despite appropriate topical treatment, a full examination should be done, including required blood tests and imaging, to rule out internal malignancy. While the cancer is being treated, topical steroids and emollients may alleviate the skin scaling and reduce the lesion thickness. Some researchers have used vitamin A analogs or vitamin D derivatives, or calcipotriol, to help normalize epidermal growth along with definitive or palliative treatment of the tumor, depending on the stage of the cancer. In most cases, unfortunately, diagnosis is made after metastasis has already occurred, and the mortality is high in this condition due to the underlying cancer.