Acrokeratosis paraneoplastic L85.1

A skin disease belonging to the so-called obligate paraneoplasias, associated with chronically persistent, erythematosquamous, hyperkeratotic plaques on the acras. In the majority of cases with Bazex syndrome, the skin lesions precede the diagnosis of the primarius, whereas in approximately 15% of patients, the skin lesions developed after the diagnosis of the neoplasm. The skin lesions have also been described in association with multiple myeloma (Kandemir Alibakan Ö et al. 2020). A clinically confirmed diagnosis has a high diagnostic relevance.

The pathogenesis of Bazex syndrome is unknown. Some authors suggest an immunological mechanism based on the detection of immunoglobulins (IgG, IgA, IgM) and complement (C3) along the basement membrane of affected and healthy skin. An immune response to a common antigen (skin and tumor) has been suggested (Bolognia JL et al 1991). Furthermore, it has been suggested that underlying malignancies may be associated with a shift to a Th2 immune pathway, which in turn may lead to increased expression of epidermal growth factor receptors in affected keratinocytes (Amano M et al 2016).

Risk factors for Bazex syndrome include tobacco and alcohol use (Räßler F et al. 2017).

Various growth factors produced by the primarius, such as tranforming growth factor-alpha, as well as other growth factors, appear to be responsible for epithelial cell proliferation.

Associated malignancies are mainly epithelial carcinomas, such as squamous cell carcinomas of the tongue, pharynx, larynx, esophagus (39% of cases); other malignancies are squamous cell carcinomas of the lung (11%), adenocarcinomas of the lung (4%), gastrointestinal adenocarcinomas (8%), genitourinary tumors (5%), and lymphomas. Skin lesions have also been described in association with multiple myeloma (Kandemir Alibakan Ö et al. 2020).

Associated malignancies are mainly epithelial carcinomas, such as squamous cell carcinomas of the tongue, pharynx, larynx, esophagus; furthermore small cell lung carcinoma (Hoepffner N et al. 1992). The skin changes have also been described in association with multiple myeloma (Kandemir Alibakan Ö et al. 2020).

Finger and toe ends, nails, nose, auricle; in the late stage extensive spreading to the whole integument possible.

Scaly, indistinct, symmetrical, non-pruritic, psoriasiform plaques, later edematous swelling of the acras. Rarely, bullous lesions may also occur. Lesions occur preferentially on acral sites such as the fingers (61%), toes (39%), ears (79%), and nose (63%). The nails are almost always affected, are no different from the nail changes seen in psoriasis, and are often the first sign of the disease. Erythematosus-like skin changes may occur on the face. If the condition persists for a long time, it may spread to the entire skin surface. In this case, psoriasiform clinical pictures develop.

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

Recent studies demonstrate localized deposition of complement factors, immunoglobulins, and fibrin at the basement membrane.

Lupus erythematosus

Psoriasis vulgaris

Pityriasis rubra pilaris

Spiny hyperkeratosis (in multiple myeloma)

Medical history: 65-year-old patient; since 6-8 months increasing, symptomless keratinization disorders on palms of hands and soles of feet /here painful under stress (pain was the cause of the visit to the doctor). At the same time increased keratinization of the areolae mammae and multiple seborrhoid keratoses in the sternal area and on the back.

Findings: Painless keratoses up to 0.2 - 0.4 cm in size, distributed over both palms, firmly adherent, yellow-brownish, partly wart-like, partly flatly sunken keratoses. At pressure sores there is extensive aggregation of the keratoses. Here "spike-like" aspect. Occasionally also "cornu-cutaneum-like". Endoscopic evidence of a previously unknown adenocarcinoma of the colon.

Comment: An acquired, generalized keratinization disorder of the skin which occurs unusually fast should always be the reason for a thorough general tumor diagnosis.

1. Amano M et al (2016) Bazex syndrome in lung squamous cell carcinoma: High expression of epidermal growth factor receptor in lesional keratinocytes with Th2 immune shift. Case Rep Dermatol 8:358-362.

2. Bazex A, Salvador R, Dupré A, Christol B (1965) Syndrome paranéoplasique à type d'hyperkératose des extrémités. Guérison après le traitement de l'épithélioma laryngé. Bull Soc Franc Derm Syph 72: 182

3. Bolognia JL et al (1991) Bazex syndrome (acrokeratosis paraneoplastica). An analytic review. Medicine (Baltimore) 70:269-280.

4. Buxtorf K et al (2001) Bazex syndrome. Dermatology 202: 350-352

5. Gill D et al (2001) Bullous lesions in Bazex syndrome and successful treatment with oral psoralen phototherapy. Australas J Dermatol 42: 278-280
6. Hinzenstern v J et al (1990) Paraneoplastic acrokeratosis Bazex - course under palliative therapy of a tongue base carcinoma. Dermatologist 41: 490-493
7. Hoepffner N et al (1992) Special form of acrokeratosis Bazex in small cell bronchial carcinoma. Dermatologist 43: 496-499
8. Kandemir Alibakan Ö et al (2020) An Unconventional Presentation of Multiple Myeloma: Bazex Syndrome. Turk J Haematol 37: 294-296.
9. Kofler L e, Kofler H (2015) Acrokeratosis paraneoplastica Bazex 6 years before diagnosis of gastric carcinoma. Dermatologist 66: 542-544

10. Räßler Fet al. (2017) Acrokeratosis paraneoplastica (Bazex syndrome) - a systematic review on risk factors, diagnosis, prognosis and management. J Eur Acad Dermatol Venereol 31:1119-1136.