Acrokeratosis Paraneoplastica with Adenocarcinoma of the Colon Treated with Topical Tretinoin: DISCUSSION
Acrokeratosis paraneoplastica is an example of a paraneoplastic syndrome which reflects an underlying malignancy. The clinical manifestations include palmoplantar keratoderma, violaceous psoriasiform papulosquamous lesions, hyperpigmentation, and nail dystrophy. Acrokeratosis paraneoplastica has a characteristic symmetric bilateral acral distribution, primarily affecting white males of French extraction over 40 years of age. The most common associated neoplasms are squamous cell carcinoma of the upper respiratory tract and other tumors with cervical lymph node metastases. Also, various kinds of neoplasms in association with this syndrome are re¬ported, including prostate adenocarcinoma, bladder carcinoma, thymic carcinoma, squamous cell carci¬noma of the leg, breast carcinoma, hepatocellular carcinoma, vulvar carcinoma, lymphoma, and multiple myeloma3. Thus far, only one case asso¬ciated with colon cancer has been reported in the English literature. Involvement of the nails appears in more than three-quarters of the cases, with subungal hyperkeratosis, ridging, thickening, onycholy- sis, pigmentation, anonychia, and onychomadesis.
The histological findings are non-specific, most frequently showing hyperkeratosis, parakeratosis, and acanthosis. A perivascular lymphohistiocytic inflammatory infiltrate, vacuolar degeneration of the basal layer, and a few dyskeratotic keratinocytes may also be seen. Immunofluorescence studies of lesional skin from patients are usually negative, but Pecora et al described IgG, IgM, IgA, and C3 deposition along the basement membrane zone of lesional and non-lesional skin by direct immunofluo- rescence. cialis super active
The psoriasiform skin lesions are known to precede the diagnosis of neoplasm in over 60% of the patients. Cutaneous manifestations follow the diagnosis of neoplasm in 15% of patients. Bazex and Griffiths divided acrokeratosis paraneoplastica into three clinical stages. In stage 1, ill-defined erythema and scaling involves the fingers, nose, toes, nails, and the helices of ears. The tumor is asymptomatic during this stage. In stage 2, local symptoms occur. The skin lesions tend to spread to the palms, soles, and cheeks. If the tumor remains untreated, the skin lesions may expand to the arms, legs, and trunk in stage 3.
The pathogenesis of acrokeratosis paraneoplasica is still unknown. An immunologic mechanism based on the findings of immunofluerescence has been presented on the basis of immunofluorescence findings. Bazex and Griffiths suggested that cross- reactivity between tumor antigens and skin antigens leads to this syndrome. Some authors have demon¬strated that the severity of clinical manifestations of acrokeratosis paraneoplastica parallel the serum concentrations of squamous cell carcinoma antigen, also suggesting an immunologic mechanism. Bolognia reported that squamous cell lines produce TGF- a and insulin-like growth factor 1, which have a stimulatory effect on human keratinocytes. Politi et al disclosed that TGF- a levels in the urine of patients with acrokeratosis paraneoplastica decline markedly after surgery, together with clinical improvement.
Treatment with antibiotics, topical steroids, kera- tolytics, vitamin D, and PUVA achieve only transient remission. Despite some cases in which the cutaneous manifestations are completely healed by acitretin or etretinate without removal of the primary cancer, the treatment of skin lesions is directly related to eradication of the underlying neoplasm. Occasionally, a reappearance of the skin lesions signals the recurrence of the primary tumor or an appearance of skin lesions coincides with the development of metastatic disease. Nail involve¬ment usually persists long after the tumor has been successfully treated.
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In our case, the patient had persistent cutaneous manifestations after surgical extirpation of the neoplasm. We treated her with topical 0.025% tretinoin for about 2 months, which resulted in almost complete remission of the skin lesions, except for the dystrophic fingernails and toenails. We treated her with topical tretinoin because of the favorable response to many hyperkeratotic skin conditions, such as acanthosis nigricans or psoriasis. The effects of topical tretinoin on the epidermis include the induction of epidermal mitotic activity, the shedding of desmosomes and tonofibrils, and the production of a mucin-like material. These actions affect cell growth, differentiation, and morphogene¬sis and alter cell cohesiveness. Although are not studied yet, especially in acrokeratosis paraneo- plastica, these actions can account for the impro¬vement of various hyperkeratotic conditions. The case reported herein is a typical example of acrokeratosis paraneoplastica showing improvement with topical tretinoin.
Category: Cancer
Tags: Acrokeratosis paraneoplastica, Bazex syndrome, Colon Cancer, Tretinoin