Skin Disorders Guide

Diagnostic Hallmarks

1. Distribution - trunk, buttocks, and thighs
2. Stability of plaque shape and size

Parapsoriasis is not, of itself, a very important disease. It is uncommonly encountered, is not contagious, and probably is not be cured, Its importance lies in its relationship to the cutaneous T-cell lymphoma (CTCL) mycosis fungoides. These two diseases exist on a spectrum such that over a number of years the lesions of parapsoriasis tend to evolve into those of the always fatal, mycosis fungoides.

Clinical Presentations

Several vanetles of parapsoriasis exist, but only the most common one, large plaque parapsoriasis (parapsoriasis enplaque), is discussed here. The lesions of parapsoriasis consist of sharply marginated, scaling, barely elevated, red plaques.as the name suggests, the appearance of these plaques is somewhat similar to those of psoriasis. In parapsoriasis, however, the color is brown red rather than bright red, the scale is line and powdery (pityriasis type) rather than flaky; and evidence of the Koebner phenomenon is not found. Finally, the plaques of parapsoriasis are extraordinarily stable in shape and size, whereas those of psoriasis are constantly changing over a period of weeks to months.

The lesions of parapsoriasis can occur anywhere on the trunk and proximal extremities but are most commonly seen on the abdomen, buttocks, and thighs. In women the breasts are often involved. Parapsoriasis can occur at almost any age but is most commonly seen in the mid or late adult years. The lesions are usually asymptomatic.

The evolution of parapsoriatic plaques into those of the plaque stage of mycosis fungoides is marked by a gradual thickening. Scale becomes less apparent, and the brown-red color gradually develops dusky, violaceous hues. The round or oval outline of the plaques gradually takes on a more irregular shape. Indented (kidney-shaped) and polycyclic plaques develop. During this transition, histologic evidence of lymphocyte atypicality develops and clusters of these atypical cells appear within the epidermis (Pautrier microabscesses).

With the passage of additional time, nodules begin to appear. They may arise de novo or may develop within the preexisting plaques. Ulceration of the plaques and nodules commonly occurs. This “tumor” stage of mycosis fungoides is generally accompanied by the development of lymphadenopathy and other evidence of systemic involvement.

Other Forms of Cutaneous T-Cell LymPhoma. Exfoliative erythrodermatitis can occur secondary to widespread, severe psoriasis and various forms of eczematous disease . It can also arise in a primary form in mid or late adult life as a manifestation of CTCL. This form is termed Sezary syndrome. The clinical presentation in Sezary syndrome differs from secondary exfoliative erythrodermatitis in that there is often associated alopecia, palmar and plantar hyperkeratosis, and a significant degree of cutaneous hyperpigmentation. Patients with Sezarys syndrome usually have, at the onset, evidence of systemic involvement as noted by lymphadenopathy and the presence of circulating atypical lymphocytes (Sezary cells) .

Rarely, the first manifestation of CTCL is the sudden onset of multiple large nodules. This type of presentation was previously known as d’emblee-type mycosis fungoides, now it is recognized that such nodules may be made up of” phenotypically quite varied malignant T cells. These nodular lymphomas are simply termed peripheral T-cell lymPhomas.

Course and Prognosis

Parapsoriasis is an extraordinarily stable and slow-moving disease. Gradual centrifugal enlargement of individual plaques does occur, but years go by before light microscopic and clinical evidence of malignancy is seen. Patients frequently develop other health problems and die long before mycosis fungoides becomes a problem.

The course of mycosis fungoides, once present, is extremely variable. A few patients will develop evidence of systemic disease in as little as several years, but most will go for S to 10 years before tumors, ulcers, and evidence of internal involvement develop. Once these changes occur, however, the pace of the disease picks up appreciably. At that point, the clinician can predict death from the disease within 2 to 5 years. In spite of this slow and highly variable course, one thing is clear, Mycosis fungoides is inevitably fatal. One escapes death from mycosis fungoides only by dying from some other process.

Pathogenesis

The cause of parapsoriasis and that of mycosis fungoides are unknown. A current, attractive hypothesis, however, suggests that mycosis fungoides develops as an uncontrolled immunologic reaction to a persistent antigen that is deposited on or is developed in the skin. This hypothesis, which is based on the large number of Langerhans cells present in the early inflammatory infiltrate, suggests that Langerhans cells process and convey an unknown antigen to helper T-cell lymphocytes. These T cells, in turn, activate a clone of T cells that, perhaps because of persistent stimulation, eventually develops malignant characteristics. Once formed, these malignant T cells increase in number and collect first in the skin and eventually in the lymph nodes and other internal organs. In the early lesions of mycosis fungoides the proportion of malignant to benign inflammatory cells is low. In the tumor stage a much higher proportion of malignant cells is found. The transition of parapsoriasis to CTCL is marked immunophenotypically by the gradual loss of pan T-cell antigens from the mononuclear cells that make up the “inflammatory” infiltrate in the cutaneouslesions. Evidence of clonal expansion, as measured by the presence of gene rearrangement in the T-cell antigen receptor, also gradually becomes apparent.

Discovery of the human T-cell lymphotropic virus type I and other related retroviruses has added another dimension to our understanding of cutaneous T-cell lymphomas. Infection of helper T-cell lymphocytes with this virus results in eventual clonal proliferation of infected cells. It seems likely that at first this is a latent infection that only subsequently leads to transformation and proliferation.

In any event, it is apparent that CTCL, like most other forms of malignancy, develops in a stepwise manner in which one or more mutational steps are followed by both clonal expansion and, eventually, additional mutational events.

Therapy

Patients with parapsoriasis are often first treated with topically applied steroids. Unfortunately, the degree of response is usually unsatisfactory. The next step for most patients involves the use of topically applied nitrogen mustard or the administration of PUVA therapy. With either modality, approximately 80% of patients can obtain a complete cutaneous remission. These remissions usually must be maintained by continuous treatment; once therapy is stopped, relapse regularly occurs. Those who fail to respond and those who break through during treatment can be treated with electron beam radiation.

The more radical approach involves the initial use of total-body electron beam irradiation with or without additional adjuvant therapy. Complete remissions are obtained in 90% of the patients treated, and more importantly, about 20% of these patients maintain their remissions indefinitely without further therapy. Unfortunately, this approach exposes patients to a considerable amount of radiation, is time consuming, and is expensive.

Patients with evidence of systemic disease are usually given multiple-drug chemotherapy in addition to total-body electron beam therapy. Unfortunately, no matter how aggressive an approach to therapy is taken, cure is not possible in those with any evidence of systemic disease. Other treatments currently being used for CTCL include extracorporeal, photophoresis (PUVA therapy of lymphocytes) and the systemic administration of retinoids and interferon-alfa.