Acrokeratosis Neoplastica (Bazex Syndrome)

Article Author:
Joel Pulickal
Article Editor:
Feroze Kaliyadan
Updated:
11/27/2017 6:11:52 PM
PubMed Link:
Acrokeratosis Neoplastica (Bazex Syndrome)

Introduction

Bazex syndrome (acrokeratosis paraneoplastica) or acrokeratosis neoplastica (AN) syndrome is a rare, acral psoriasiform dermatosis associated with internal malignancies, most frequently squamous cell carcinoma of the upper aerodigestive tract. However, it is important to know that almost any malignancy of squamous cells can be associated with the syndrome. Thus, these patients need an exhaustive workup to determine the location of the malignancy. If the primary malignancy is not treated, not only is the prognosis poor, but the skin lesions will also fail to respond 

Etiology

The pathogenesis of Bazex syndrome is unknown. Bolognia reported that in 67% of the cases with Bazex syndrome, the cutaneous lesions predicted the diagnosis of an underlying malignancy, whereas, in 15% of the patients, the skin lesions developed after diagnosis of the neoplasm.

Epidemiology

The population most often affected is White males in their 40s. Females are rarely affected.

Pathophysiology

The pathogenesis of Bazex syndrome is unknown. Some authors have implicated an immunological mechanism based on the findings of immunoglobulins (IgG, IgA, IgM) and complement (C3) along the basal membrane of the involved and healthy skin.

Histopathology

Features in the epidermis can include spongiosis, interface change including vacuolar degeneration and dyskeratotic keratinocytes, and in the dermis, a lichenoid infiltrate, melanophages, and papillary dermal fibrosis.

Recent studies indicate that immunohistochemistry of the skin lesions will reveal localized deposits of complement factor 3, immunoglobulins, and fibrin within the basement membrane.

History and Physical

The typical clinical features are a tender, largely nonpruritic, and erythematous psoriasiform eruption that favors acral sites such as the fingers (61%), toes (39%), ears (79%), and nose (63%). Unlike psoriasis, the helical rim of the ear and nasal tip are affected. Intensive violaceous erythema, erosions, and yellowish crusts may be present. If the underlying tumor is not treated, the eruption has been seen to extend proximally. As the tumor progresses, the lesions of AN may spread and may involve the cheeks, elbows, knees, and trunk. The most common localization of malignancies is the neck and head area. Approximately 39% of the underlying malignancies were squamous cell carcinomas of the pharynx, esophagus, and larynx. The other malignancies that are found to be associated are squamous cell carcinoma of the lung (11%), adenocarcinoma of the lung (4%), gastrointestinal adenocarcinoma (8%), genitourinary tumors (5%), and lymphomas. Nail involvement is common and is typified by horizontal and vertical ridging, yellow discoloration, onycholysis, subungual hyperkeratosis, and in more severe cases, nail plate atrophy. In 63% of cases, skin lesions precede the diagnosis of the tumor by approximately one year. According to Bazex et al., the disease develops in three stages. During the first stage, mainly earlobes, the ear helix, the tip of the nose, distal fingertips, or nails are affected. Vesicles, subungual hyperkeratosis or nail dystrophy can be noted. First signs of an extracutaneous malignancy can be obvious, but usually, this is an asymptomatic stage. Later, in stage two, palms and soles are frequently involved. The skin lesions spread with the involvement of the cheeks, forehead, elbows, tights, and knees. If the underlying tumor is progressing, erythema can spread to the trunk as well in stage three.

During the physical exam, one must be aware of signs of malignancy and paraneoplastic syndromes. Features that may be indicative of malignancy include the following:

  • Pruritis
  • Ichthyosis
  • Sister Mary Joseph nodule
  • Clubbing
  • Sign of Leser-Trelat
  • Blummer shelf
  • Virchow's node

Evaluation

Upon suspicion of Bazex syndrome, a detailed patient history, and a physical examination are mandatory. A diagnostic workup, including otolaryngologic examination, chest x-ray, a complete blood cell count, serum and urine protein electrophoresis, an erythrocyte sedimentation rate, a biochemistry profile, tumor markers (e.g., prostate-specific antigen, CEA), and a test for occult blood in the stool should be performed.

Imaging and Endoscopic Studies

  • Gastrointestinal imaging using barium
  • Chest x-ray must be done in all patients suspected of having acrokeratosis paraneoplastica
  • Ultrasound of the abdomen and pelvis
  • CT scan of the chest, head/neck, and abdomen
  • MRI of the chest, head/neck, and pelvis
  • Mammography
  • PET scan

Other tests that may be needed based on clinical presentation:

  • Upper and lower endoscopy
  • Cystoscopy
  • Bronchoscopy
  • Bone marrow biopsy
  • Lymph node biopsy

Treatment / Management

The favored therapy to eliminate the described skin lesions is the effective treatment of the underlying tumor. Paraneoplastic skin lesions as seen in Bazex syndrome do not respond to the classical dermatological therapy of inflammatory skin diseases. Improvement after the treatment with Vitamin D3, salicylic acid, etretinate, and topic or systemic steroids was reported occasionally. Reported topical ointments include topical corticosteroids, as clobetasol 0.05% or betamethasone 0.01%, salicylic acid 10% in vaseline, itraconazole, isosorbide dinitrate, fluconazole, cephalexin, keratolytic, neomycin, nystatin, zinc ointment, antibiotic, and emollients. Some authors suggest a treatment with oral dexamethasone 10 mg/day leading to a good response of the cutaneous lesions.

In the last decade, anecdotal reports indicate that use of both systemic and topical retinoids may help ease the skin lesions. These vitamin A derivatives may be combined with oral corticosteroids. Some reports indicate that the use of psoralen plus ultraviolet light therapy may be helpful in selected patients with localized skin lesions.

There are even reports indicating that supplementation of zinc may help ease the skin lesions.

Prognosis

The success of treatment of acrokeratosis paraneoplastica depends on the primary malignancy. if the malignancy fails to respond or is advanced, then the skin lesions will not respond.

In any patient with cervical lymph node metastases at the time of diagnosis, the prognosis is poor. In all cases, the morbidity of the disorder is directly related to the underlying primary malignancy and not the skin lesions.

However, overall the response to treatment is extremely variable, unpredictable, and not satisfactory.

Pearls and Other Issues

In the early stage of the disease, skin lesions often serve as an indicator for a symptomless internal malignancy. Whereas the skin lesions improve significantly after adequate tumor therapy, the nail changes often remain. The original nail growth is often reduced, and a complete remission is absent. If the tumor reoccurs or if there are metastases present, the skin lesions usually worsen again.

The management of these patients should involve a multidisciplinary team of healthcare professionals because of the varied types of cancers. Once the diagnosis is made, there should be no delay in ruling out a malignancy.