Title: Acrokeratosis paraneoplastica (Bazex syndrome): An atypical presentation
Authors:  Raghavendra Rao, and Shrutakirthi D. Shenoi
Affiliations: Department of Dermatology, Kasturba Medical College, Manipal, Karnataka India. jennyrao1@yahoo.com
Citation: DOJ Editing/Review
Abstract:
A 62 year old male  presented with a two year history of hyperkeratotic lesions of the hands and feet. Previous treatment with topical steroids was unsuccessful. A complete physical examination revealed the presence of blood in the stool and sigmoidoscopy showed an ulcerative growth at the rectosigmoid junction. The histopathology showed adenocarcinoma.
Body:
Introduction: 
<I>Acrokeratosis paraneoplastica</I> is a rare but distinctive dermatosis described by Bazex et al. in 1965. [1] It is characterized by psoriasiform erythematous plaques, typically affecting hands, feet, nose and earlobes.  The condition is associated with internal malignancy, usually squamous cell carcinoma of the upper aerodigestive tract, or cervical lymph node metastases from an unknown primary tumor. [2] Other rare associations include adenocarcinoma of the stomach, esophagus, or uterus, anaplastic small-cell carcinoma of the lung, Hodgkin's lymphoma, [3] transitional-cell carcinoma of the bladder, [4] adenocarcinoma of the colon, [5] and squamous cell carcinoma of the lower leg. [6]
I: Case report
figure 1: 1.jpg

A 62-year-old male presented with complaints of itchy, scaly lesions of hands and feet for two years. He initially developed pruritic vesicles and scaly plaques in the periungual areas of the right foot. Later, similar lesions appeared on the left foot and on both hands. Various topical steroids had no effect on the lesions.
Examination disclosed multiple hyperpigmented scaly papules and plaques over the dorsum and palmoplantar surfaces of the hands and feet(Fig. 1).  Examination of the nails showed thickening and brownish discoloration of nail plates with subungual hyperkeratosis involving a few nails of the hands and feet.
Routine laboratory examination of blood and urine was normal, but an examination of stool showed frank blood on two occasions.  Sigmoidoscopy showed an ulcerative growth at the rectosigmoid junction. A biopsy of that lesion revealed well-differentiated adenocarcinoma.
Skin biopsies of palmar and plantar lesions showed gross hyperkeratosis, acanthosis, and regular psoriasiform-elongation of rete ridges. PAS staining did not reveal dermatophytes. Though nail clippings were positive for dermatophyte, KOH preparations from palms and soles were negative. Treatment for one month with fluconazole, 150 mg per week, did not produce any improvement in the appearance of the palms and soles.   

I: Discussion
Acrokeratosis paraneoplastica is a rare paraneoplastic syndrome. [7] Its presence should therefore prompt an extensive search for occult cancer. It is more common in males, with mean age of onset around age 61 years. The skin eruption precedes the detection of an underlying malignancy in 67 percent of cases, with a reported median interval of as long as one year between the onset of the skin changes and the recognition of malignancy. Cutaneous manifestations follow the diagnosis of malignancy in 15 percent of cases. In the remainder, the onset of skin lesions and the diagnosis of the tumor occur concurrently. Usually the course of the dermatosis parallels that of the tumor growth; the skin eruption resolves only when the tumor is effectively treated. [6]
Bazex & Griffith [1] described the three stages of evolution of the disease:
*Stage I.  Erythema and psoriasiform scaling of fingers and toes, ear helices and nose are present. There are also nail changes, including subungual hyperkeratoses, onychodystrophy, longitudinal bands of discoloration, and onycholysis.
*Stage II. Involvement of palms and soles is common. Facial lesions involve cheek and pinna. Malignancy usually becomes evident in this stage.
*Stage III.  Involvement extends to legs, knees, thighs, arms, trunk and scalp.

Associated features of acrokeratosis paraneoplastica include pruritus, sterile paronychia, vesicles and bullae, hyperpigmentation, hypopigmentation, and carpal tunnel syndrome. [3] The diagnosis is based on clinical features since the histopathology is non-specific [8]. Pecora et al. described IgG, IgM, IgA, and C3 along the basement membrane zone of lesional and non-lesional skin by direct immunofluorescence. [2] However, others could not reproduce these results. [8]
Our case is unusual because the eruption lacked erythema and was limited to acral areas with sparing of ears and nose. The associated internal malignancy was an adenocarcinoma of the rectosigmoid junction and not the usual squamous cell carcinoma. To our knowledge, there is only one report of such an association.

References: 
1. Bazex A, Griffith A. Acrokeratosis paraneoplastica : A new cutaneous marker of malignancy.  Br. J. Dermatol 1980;103:801-805.
2. Andrew L Pecora, Larry Landsman, Stephen Imgrund, Clark Lambert. Acrokeratosis paraneoplastica. Arch. Dermatol 1983;119:820-826.
3. G P H Lucker and P M Steijten. Acrokeratosis paraneoplastic occurring with acquired ichthyosis in Hodgkin's disease. Br. J. Dermatol 1995;133:322-325.
4. Arregui MA, Raton JA, Landa N, Izu R, Eizaquirre X, Diaz - Perez JL.  Bazex syndrome (Acrokeratosis paraneoplastica) - first case report of association with bladder carcinoma. Clini, Ex. Dermatol 1993; Sept 18 (5) : 445-8.
5. Hsu YS, Lien GS, Lai HH, Cheng YS, Hu CH, Hseih MC, Fang CL, Pan S. Acrokeratosis paraneoplastica (Bazex syndrome) with adenocarcinoma of the colon : report of a case and review of the literature. J Gastroenterol 2001;35(6):460-4.
6. M Hara, M Hunayama, S Alba, T Suetake, M Watanabe, M Tanaka and H Tagami. Acrokeratosis paraneoplastica (Bazex syndrome) associated with primary cutaneous squamous cell carcinoma of the lower leg, vitiligo and alopecia areata. Br. J. Dermatol  1995;133:121-124.
7. Bolognia JL. Bazex syndrome (Acrokeratosis paraneoplastica). Semin Dermatol 1995 Jun; 14(2):84-99.
8. Marie Richard and Jean Maris Giroux. Acrokeratosis Paraneoplastica (Bazex syndrome).  J Am Acad Dermatol 1987;16:178-83.