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Observation
June 2015

Acute Onset of Acrokeratosis Paraneoplastica (Bazex Syndrome)

Author Affiliations
  • 1Department of Dermatology, Medical College of Wisconsin, Milwaukee
  • 2Department of Medicine, Medical College of Wisconsin, Milwaukee, Milwaukee, Wisconsin
  • 3Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee
JAMA Dermatol. 2015;151(6):677-678. doi:10.1001/jamadermatol.2014.5622

Acrokeratosis paraneoplastica, or Bazex syndrome, is a well characterized but rare dermatosis first described by Bazex et al1 in 1965 in association with a malignant neoplasm of the upper aerodigestive tract. It is typically seen in men older than 40 years.25

Report of a Case

A 57-year-old man sought medical attention for dysphagia, chest pain, and a 40-lb weight loss over 6 months. Imaging demonstrated a distal esophageal ulcerating mass covering 50% to 75% of the esophageal circumference. Biopsy showed a poorly differentiated epithelioid malignant neoplasm; immunohistochemical staining was negative for pan-cytokeratins, melanoma, and mesenchymal markers.

On physical examination, the patient had desquamative, edematous digits of the hands and feet with hyperpigmented, lichenified plaques. He had numerous grouped and clustered tense vesicles (1-3 mm) and a few hemorrhagic bullae (Figure 1). He also had an ill-defined hyperkeratotic, violaceous patch on his nose and small vesicles on the ears. His knees exhibited hyperpigmented hyperkeratotic plaques. The patient reported that his cutaneous manifestations developed in less than a week.

Figure 1.
Clinical Vesicle Formation in a Patient With Acrokeratosis Paraneoplastica
Clinical Vesicle Formation in a Patient With Acrokeratosis Paraneoplastica

The hand highlights the impressive edema, desquamation, hyperkeratotic and lichenified plaques, and extensive vesicle and bullae formation.

Biopsy specimens from the wrist showed an acanthotic and mildly spongiotic epidermis with minimal interface, vacuolar damage, and overlying parakeratosis (Figure 2). In the dermis, there was an increased number of eosinophils and pigment incontinence. Direct immunofluorescence demonstrated broad-based band staining of fibrin at the basement membrane zone and granular deposits of C3.

Figure 2.
Histologic Specimen From the Wrist Showing Acrokeratosis Paraneoplastica
Histologic Specimen From the Wrist Showing Acrokeratosis Paraneoplastica

At low magnification (×40), there is an acanthotic and mildly spongiotic epidermis with minimal interface, eosinophils in the dermis, and overlying parakeratosis (hematoxylin-eosin).

Skin-directed therapies included a brief course of oral prednisone, clobetasol ointment, and aluminum acetate soaks, with mild improvement in discomfort and appearance of the skin lesions. Systemic chemotherapy was initiated to treat the metastatic, poorly differentiated epithelioid malignant condition. The patient also received palliative radiation therapy to the esophagus and salvage systemic therapy, but he died after 4 months.

Discussion

Acrokeratosis paraneoplastica is a rare paraneoplastic phenomenon with characteristic findings, though its pathogenesis and relationship to the associated malignant condition are not well understood. Theories include tumor antigens cross-reacting with antigens of the skin BMZ, a cellular immune response with cytotoxic effects, tumor growth factors inducing hyperkeratosis (transforming growth factor α, epidermal growth factor, or insulin-like growth factor 1), or zinc and vitamin A deficiency from tumor expansion.5,6

The eruption is generally symmetric and nonpruritic, with violaceous to pink patches and plaques with hyperkeratosis of acral sites.35 The extremities and trunk can be involved.36 The palms and soles may have hyperkeratosis and fissures, as in keratoderma.5 Nail changes are frequently seen, including onycholysis and subungual debris.4 Edema of the distal extremities and vesicular formation is infrequently seen.3,5,7

The cutaneous manifestations present, on average, 11 months prior to the discovery of cancer, but in 20% of the cases, the malignant neoplasm is diagnosed at the time of the skin eruption.5,6 Squamous cell carcinoma is the most commonly associated malignant condition.6 Other cancers include poorly differentiated carcinoma, adenocarcinoma, small cell carcinoma, lymphoma, and cholangiocarcinoma. The majority of associated malignant neoplasms occur above the diaphragm and involve the upper one-third of the aerodigestive tract.

Bazex syndrome may resemble more common diseases such as psoriasis. Therefore, a biopsy is generally helpful, though the findings are typically nonspecific. Common reported findings include hyperkeratosis, acanthosis, parakeratosis, dyskeratotic keratinocytes, and perivascular infiltrates.4,5 Immunofluorescence has been performed in a minority of cases, and its results are generally nonspecific.5 Our patient’s clinical findings were concerning for a blistering disease, but neither hematoxylin-eosin nor direct immunofluorescence evaluation showed evidence of bullous pemphigoid or paraneoplastic pemphigus.

Symptomatic improvement can be achieved by treating the underlying malignant condition; return of skin lesions can signal tumor recurrence.5 While skin-directed therapy might be helpful to control symptoms, the responses are variable and suboptimal.

In summary, we present herein a case of acrokeratosis paraneoplastica with rapid onset of cutaneous findings and the development of many vesicles and bullae. Furthermore, we demonstrate the diagnostic role of biopsy and immunofluorescence testing in this patient.

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Article Information

Corresponding Author: Stephen R. Humphrey, MD, Department of Dermatology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226 (shumphre@mcw.edu).

Published Online: March 11, 2015. doi:10.1001/jamadermatol.2014.5622.

Conflict of Interest Disclosures: Dr George serves as a consultant to Celgene and Cook Medical. No other disclosures are reported.

Correction: This article was corrected on March 25, 2015, to add the middle initial to the name of author Amara S. Hussain, MD.

References
1.
Bazex  A, Salvador  R, Dupré  A,  et al.  Syndrome paranéoplasique à type d'hyperkératose des extrémités: guérison après le traitement de l'épithélioma laryngé. Bull Soc Fr Dermatol Syphiligr. 1965;72:182.
2.
Bazex  A, Griffiths  A.  Acrokeratosis paraneoplastica: a new cutaneous marker of malignancy. Br J Dermatol. 1980;103(3):301-306.
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Pecora  AL, Landsman  L, Imgrund  SP, Lambert  WC.  Acrokeratosis paraneoplastica (Bazex’ syndrome): report of a case and review of the literature. Arch Dermatol. 1983;119(10):820-826.
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Bolognia  JL.  Bazex’ syndrome. Clin Dermatol. 1993;11(1):37-42.
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Bolognia  JL, Brewer  YP, Cooper  DL.  Bazex syndrome (acrokeratosis paraneoplastica): an analytic review. Medicine (Baltimore). 1991;70(4):269-280.
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Karabulut  AA, Şahin  S, Şahin  M, Ekşioğlu  M, Ustün  H.  Paraneoplastic acrokeratosis of Bazex (Bazex’s syndrome): report of a female case associated with cholangiocarcinoma and review of the published work. J Dermatol. 2006;33(12):850-854.
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Schoeffler  A, Sagot  V, Marzin  A,  et al.  Bullous paraneoplastic acrokeratosis [in French]. Ann Dermatol Venereol. 2006;133(6-7):557-560.
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