The nosology of parapsoriasis

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VOLUME 5

NUMBER 4

OCTOBER, 1981 II I

Continuing medical e d u c a t i o n The nosology of parapsoriasis W. Clark Lambert, M.D., Ph.D., and Mark Alien Everett, M.D.

Newark, N J, and Oklahoma City, OK Parapsoriasis is a group of uncommon but not rare disorders that was created in 1902 as part of a now long forgotten scheme to classify all inflammatory dermatoses. This artificial grouping has led to an enormously confused nosology of these disorders, that are, for the most part, otherwise unrelated. The use of a number of different terms at different institutions and by different physicians to denote the same diseases, together with the use of particular, single terms to denote different diseases, has caused much unnecessary confusion. In this review these terms are examined and an attempt is made to propose a new, unambiguous classification. Using this system, physicians with different views regarding which of the parapsoriases constitute distinct entities should have no difficulty communicating, and should have a clearer frame of reference within which to work. An attempt is made to evaluate critically which of the parapsoriases are distinct entities and whether one or more of them should be considered an early form of cutaneous lymphoma in light of currently available data. (J AM ACAD DERMATOL5:373-395, 1981.)

Dermatologic nomenclature is considered by many physicians to be the most confusing in all of medicine, and dermatologists as a whole consider the most confusing nomenclature in dermatology to be that of parapsoriasis. Whereas the opinion of the average physician regarding dermatologic

From the Departments of Pathology (Dermatopathology) and Medicine (Dermatology), CMDNJ-New Jersey Medical School, Newark, and the Departments of Dermatology and Pathology, University of Oklahoma Medical Center, Oklahoma City. Reprint requests to: Dr. W. Clark Lambert, Medical Science Bldg., C520, Department of Pathology (Dermatopathology), CMDNJNew Jersey Medical School, 100 Bergen St., Newark, NJ 07103. 0190-9622/81/100373+23502.30/0

9 1981 Am Acad Dermatol

nomenclature is at least partially based on ignorance of the subject, even dermatologists who 'are keenly versed in the entities that comprise the parapsoriasis group find the nomenclature difficult. This confusion regarding the parapsoriases is important, because the entities that comprise this group are not rare, and of these, one progresses to cutaneous l y m p h o m a in about 10% of cases, another may exist in a form that histologically resembles a l y m p h o m a and which m a y quite rarely progress to a lymphoma, and a third never progresses to a lymphoma. In addition, one important variant, although rare, appears rather regularly to progress to a cutaneous l y m p h o m a . Thus it is ira373

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portant that these entities be distinguished from each other and that communication between physicians be unencumbered. For this reason the present review is presented. It represents a consensus of the views reached by the authors in our recent separate reviews~.2 of the subject. Although both of us have modified our previous opinions somewhat, a few differences remain between our views. This should in no way detract from the usefulness of this review, the primary purpose of which is not to answer questions so much as to eliminate the trivial ones, especially where they obscure more substantive issues, and to bring these more important questions into focus. I. THE PROBLEM

There are four types of controversy regarding the nosology of the parapsoriases. First, there are differences of opinion as to whether certain of them are distinct entities or should be considered an early stage of one or more types of cutaneous lymphoma. Second, there is disagreement regarding whether certain of them should be considered separate or as variants of the same entity. Third, there are differences of opinion as to which of several terms is most appropriate to designate a given entity. Fourth, some authors use a given term to denote one of the parapsoriases, whereas other authors use the same term to indicate an entirely different one. The first and second of these areas of controversy reflect genuine differences of opinion that have biologic and diagnostic relevance, but that, if understood, should not lead to confusion or difficulties in communication between physicians who do n6t share the same viewpoint. The third and fourth areas of controversy, however, reflect purely semantic differences that have absolutely no relevance to the biology of the diseases but that are responsible for most of the confusion surrounding the nosology of parapsoriasis. Problems arising from these latter two areas are constant obstacles to communication between physicians and obfuscate controversies in the first two areas, the understanding of which is otherwise usually quite straightforward. It is the goal of this review to eliminate the latter areas of controversy as much as possible, and where not possible to

Journal of the American Academy of Dermatology

provide a reference, a sort of "Rosetta stone" of parapsoriasis, which physicians using older or ambiguous terminology, or communicating with those who do, may use in order to facilitate communication. lI. HISTORICAL DEVELOPMENT Unna et al, a in 1890, were probably the first to describe one of the parapsoriases. Theirparakeratosis variegata appears to have been the first case reported of the variant of large plaque parapsoriasis which we have denoted retiform parapsoriasis. In 1894, in two separate reports less than twenty pages apart in the very same journal, Neisser '~ (better known for his work on Neisseria gonorrhoeae), and Jadassohn, ~ his former junior associate, independently described pityriasis lichenoides. Interestingly, both authors included in their report cases of what would now be considered both acute and chronic variants of the disease. Juliusberg ~; redescribed chronic pityriasis lichenoides in 1899 and designated it a separate entity, pityriasis lichenoides chronica. In 1897, Brocq 7 described both large plaque parapsoriasis and small plaque parapsoriasis together as a single entity which he named drythrodermies pityriasques en plaques dissdmindes. The first attempt to relate all of these diseases was by Fox and Macleod 8 in 1901, who grouped these and some other reported entities together under the title resistant maculopapular scaly erythrodermias. They in no way related these disorders, however, except for their being persistent, being either macular or papular or both, being more or less erythematous, and having variable scale. They appear to have been primarily concerned with the differential diagnosis of different diseases presenting in this manner, rather than with actually classifying or reclassifying them. It was in this context that Brocq, in 1902, :~proposed the term parapsoriasis for the first time. It is most helpful, if one is to understand the current nosology of parapsoriasis, to know precisely what Brocq did and did not mean by this new name and the way in which he used it. First, he did not intend it to denote a new disease, but rather a group of separate diseases, all of which had been

Volume 5 Number 4 October, 1981

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Fig. 1. Brocq's 1902 scheme for parapsoriasis and the inflammatory dermatoses. described previously, and which had certain features in common. Those features were, essentially, unknown etiology, chronicity, failure to respond to therapy, and lack of symptoms, particularly of pruritus. Second, since he considered these features also characteristic of psoriasis vulgaris, he conceived the term parapsoriasis to denote the group, but it was these characteristics in common, rather than a resemblance on clinical examination of the lesions to those of psoriasis, that was implied by the prefix "para." Although Brocq thought that pityriasis lichenoides, which he termed ' 'l)arapsoriasis en gouttes" [in drops], had a slight resemblance to psoriasis guttata, he related the other two entities which he included under parapsoriasis, "parapsoriasis en plaques" (small plaque and large plaque parapsoriasis) and "parapsoriasis licheno?de" (retiform parapsoriasis), to seborrheic dermatitis and lichen planus, respectively. Third, the proposal of this new group of diseases was not so much because of a relationship

between them as that it was the central link of an ambitious scheme to classify and relate all inflammatory dermatoses. The grand design, taken from Brocq's original paper, 9 is reproduced as Fig. 1. It is thus clear that parapsoriasis is not a disease, and as a group of diseases is not a logical grouping, having been proposed as a deus ex machina to hold together a now long forgotten reclassification of all dennatoses. On the basis of his scheme, Brocq considered intermediate cases possible not only between the three diseases he grouped under parapsoriasis but also between them and such other disorders as psoriasis and seborrheic dermatitis; therefore, such claims should not mislead one to believe that he considered parapsoriasis a single entity. Possibly to emphasize that it represented a group of disorders, he titled his paper with the plural article " l e s , " although he kept the word "parapsoriasis" singular, as "Les Parapsoriasis. ''~ Radcliffe-Crocker, in 1905, l~ described an en-

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tity consisting of symmetrical, palisaded, yellowish, oval, macular or papular, slightly scaly lesions appearing over the trunk. He named this " n e w " disease xanthoerythrodermia perstans. It appears to be either a variant of small plaque parapsoriasis or of digitate dermatosis, discussed below, if one chooses to accept this latter entity (vide infra, sections I/I and IV, A5). In 1916, Mucha 11 redescribed acute pityriasis lichenoides as an entity separate from both chronic pityriasis lichenoides and from other diseases. Habermann, in 1925, '~ gave this "entity" the name pityriasis lichenoides et varioliformis acuta. This division of pityriasis lichenoides into two entities remains a controversial issue; one of us (M. A. E.) previously classified it as a single entity, 2 and the other (W. C. L.) as two diseases, as above, although with the notation that it may be more correct to consider it a single disease.l On the basis of published reports of cases evolving from the one to the other form, and of intermediate cases, however, 2'~3-1~ it seems more appropriate to consider pityriasis lichenoides a single entity with acute and chronic variants. In 1928, Wise 16attempted to tabulate all previous case reports of diseases grouped under parapsoriasis. His encyclopedic classification, in which he deferred grouping together entities that had been described under different titles, has been carried forward in a number of reviews in which new entities have appeared and both old and new have disappeared from time to time. lr-~o A derivative scheme proposed by Sutton in 1956, TM listing twelve separate entities, is shown as Table I. Pityriasis lichenoides was distinguished, on clinical grounds, as separate from the other parapsoriases and removed from the group by Wile in 1926, 20 Keil in 1938, ~8 Lapiere in 1948, 21 Civatte in 1951,22 and Ingrain in 1953, 23 and on histologic grounds independently by Szymanski, 24 Kruger, '~'~ and Weise 26 in 1959. Most authors today consider pityriasis lichenoides separate from the other parapsoriasesl'~a; its nomenclature is nonetheless reviewed here because of its frequent confusion with them, because of overlapping terminology (vide infra, section IV, A2) and because there is

Journal of the American Academy of Dermatology

some evidence that they may be related to each other after all (~7; vide infi'a, section IV, A2). Palmer, in 1962,28 definitively separated large plaque parapsoriasis (in which he included retiform parapsoriasis) from small plaque parapsoriasis. This same separation had been made almost a decade before by Degos, 29 who in his textbook, Dermatologie, depicted small plaque and large plaque parapsoriasis in separate figures with different titles, but in Degos' written text the two were not clearly defined as separate entities. The distinction between these entities is, of course, critical because of the malignant potential of one of them but not of the other. More recent events are discussed in the following sections. III. DEFINITION OF THE DISEASES

Currently, no two textbooks or references agree regarding which entities constitute the parapsoriases, and our respective chapters in separate major reference texts are ,no exception to this rule. ~.2 On the basis of our independent reviews of the subject and of our collective experience, however, we have derived a consensus that we hope will form the basis for a standard nomenclature; we propose it below. More extensive clinical and histologic descriptions may be found in our respective chapters, 1'2 as well as in the excellent review of pityriasis lichenoides by Nigra and Soter. 1.3 Depending upon whether one wishes to classify pityriasis lichenoides as within the parapsoriasis group, parapsoriasis is a group of either two or three entities, each with two distinct subtypes, as follows: Pityriasis lichenoides Acute (synonyms: pityriasis lichenoides et varioliformis acuta; PLEVA; PLVA; Mucha-Habermann disease) Chronic (synonym: pityriasis lichenoides chronica) Small plaque parapsoriasis Variant: Digitate dermatosis Variant (of digitate dermatosis): Xanthoerythrodermia perstans Large plaque parapsoriasis (synonyms: atrophic parapsoriasis; poikilodermatous parapsoriasis)

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Variant: Retiform parapsoriasis (synonyms: variegate parapsoriasis, parakeratosis variegata) The terms given as synonyms, above, are perfectly acceptable and in fact one of us (M. A. E.) favors atrophic parapsoriasis over the term listed. In our opinion, these are to be preferred to the other terms in current use given in Table II, because of their more frequent usage. The acute and chronic forms of pityriasis lichenoides are clinically distinct, but, on the basis of overlapping and crossover cases, appear to be variants of the same entity. 2'1:3-1'~ Digitate dermatosis is distinct in clinical appearance from small plaque parapsoriasis, but it has an identical histologic appearance, symptomatology, course, response to treatment, and prognosis. Similarly, retiform parapsoriasis is identical to typical large plaque parapsoriasis except for clinical appearance and the important additional qualification that it has a much greater potential to progress to a malignant process than does large plaque parapsoriasis considered as a whole. This difference becomes much smaller if retiform parapsoriasis is compared with cases of large plaque parapsoriasis that show a similar degree of atrophy, however. "Lumpers" would ignore all but the major headings above, accepting only three entities from the group. "Splitters" would ignore the major headings, as such, above and accept six or seven separate entities. It turns out to make remarkably little difference which approach is adopted, although the greater malignant potential of retiform parapsoriasis must be kept in mind whether or not it is considered a separate entity. Xanthoerythrodermia perstans is only a color (yellow) variant of digitate dermatosis and is thus probably a superfluous term. Whatever classification one assumes, we suggest that the terms proposed here be adopted to the exclusion of others, many of which, as we shall see, are ambiguous in use, interpretation, or original definition. All of the parapsoriases are uncommon but not rare diseases which, as pointed out by Brocq, '~are asymptomatic, of unknown etiology, respond poorly if at all to therapy, and, with the possible exception of acute pityriasis lichenoides, are chronic. The entities and their variants are further

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Table I. Sutton's 1956 classification of parapsoriasis* A. Guttate 1. Parapsoriasis en gouttes (Brocq) 2. Dermatitis psoriasiformis nodularis (Jadassohn) 3. Pityriasis lichenoides chronica (Juliusberg) B. Retiform 1. Parapsoriasis licheno~de (Brocq) 2. Parakeratosis variegata (Unna, Santi and Pollitzer) 3. Lichen variegatus (Crocker) C. Plaque 1. Parapsoriasis en plaques (Brocq) 2. Erythrodermie pityriasique en plaques dissrmin~es (Brocq) 3. Xantho-erythrodermia perstans (Crocker, C. J. White) D. Parapsoriasis atrophicans (Kreibich) E. Pityriasis liehenoides et varioliformis acuta (Habermann) F. Mixed *From Sutton RL: Diseases of the skin, St, Louis, 1956, The C. V, Mosby Co.; adapted from Wise F: NY State J Med 28:901, 1928.

defined as follows (Table III); more extensive descriptions are found elsewhere as noted above. 1,2,1a Pityriasis lichenoides is composed of generalized erythematous or brown, often hemorrhagic, scaly papules and small macules which either persist for many months or recur in periodic acute exacerbations. Few or many lesions may be present. Lesions are predominantly present over the trunk and flexural surfaces of the extremities. Acute pityriasis lichenoides is characterized by lesions as above, appearing within a few days and continuing to appear for from a few weeks to a few months. The lesions present at any one time are therefore at many different stages of evolution, and include vesicular, pustular, and sometimes necrotic (varioliform) lesions, as well as the types described above (Figs. 2 and 3). Low-grade fever, generalized lymphadenopathy, and malaise are also present occasionally. Pigment changes may be a sequela of the lesions (Fig. 4), which heal with scarring. Chronic pityriasis lichenoides is characterized by lesions as described above which are less se-

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Parapsoriasis

vere, but sometimes more scaly, less variable, and much more chronic than those of the acute variant (Fig. 5). Necrotic and vmiolifoma lesions are absent. The individual lesions last for several weeks; the entire process, however, may last for years with exacerbations and remissions common. Small plaque parapsoriasis is characterized by well-defined, roughly round to ovoid, slightly scaly, nonatrophic, nonindurated, erythematous, yellow or brown macules or very thin plaques, most of which are less than 5 cm in diameter, with a few larger lesions sometimes seen, particularly on the extremities (Fig. 6). Most of the lesions are on the trunk and proximal aspects of the extremities. In digitate dermatosis the lesions are elongated (digitate) and show a marked tendency to palisading (Fig. 7). In xanthoep:ythrodermia perstans, the lesions are identical to those of digitate dermatosis but are of yellow color (Figs. 7 and 8).

Large plaque parapsoriasis (atrophic parapsoriasis) is characterized by large, ill-defined, irregularly shaped erythematous to brown macules or plaques which are usually, but not always, associated with epidermal atrophy in at least part of the lesion (Figs. 9 to 11). Most are greater than I0 cm in diameter. The lesions tend to be on the buttocks, thighs, flexural surfaces, and, in women, over the breasts. Pigmentary changes, telangiectasias, and widespread fine scaling over the

379

lesions are characteristic (Fig. 11). Reti]brm parapsoriasis is characterized by a widespread lesion, associated with a severely atrophic epidermis, consisting of fine, 1- to 2-ram flat-topped scale-covered papules which coalesce in a netlike or retiform pattern (Figs. 12 and 13). The papules may disappear to leave macular, but usually still netlike, lesions. Retiform lesions may appear together with, and may blend with, the characteristic large plaques described above. Histologically (Fig. 14), acute pityriasis lichenoides is characterized by broad areas of parakeratosis with focal epidermal necrosis, often of single cells, which may lead to formation of vesicles. The small blood vessels in the papillary dermis are dilated and extravasation of erythrocytes is often prominent. A dense lymphobistiocytic perivascular inflammatory infiltrate is present in the papillary dermis and in a wedge-shaped distribution, with the apex in the reticular dermis beneath the lesion; such cells also may be present in the epidermis. As the disease progresses, there is thickening of the walls of the involved blood vessels leading to occlusion, more extensive hemorrhage, more widespread epidermal necrosis with ulcers overlaid by a hemorrhagic crust, and obscuring of the dermoepidermal junction by the inflammatory infiltrate, with subepidermal vesicle formation where this is severe. In the chronic form of the disease the necrosis and vascular occlusion

Fig. 2. Acute pityriasis lichenoides: Widespread lesions in varying stages of evolution. Some lesions are ulcerated and crusted. (The large lesion in the center is not a biopsy wound.) In many cases, only a few lesions are present, but the varying stages of evolution are still seen. (Courtesy Dr. Joseph B. Bikowski, Sewickley, PA.) Fig. 3. Acute pityriasis lichenoides: Close-up view of a large, hemorrhagic lesion. (Courtesy Dr. Joseph B. Bikowski, Sewiekley, PA.) Fig. 4. Acute pityriasis lichenoides, sequela: Pityriasis lichenoides may resolve with pigmentary changes and scarring which may be the chief concern of the patient. Fig. 5. Chronic pityriasis lichenoides: Lesions are similar to those of acute pityriasis lichenoides but are more chronic and do not show ulceration or hemorrhage. They are associated with a fine scale. Fig. 6. Small plaque parapsoriasis: Small, discrete, macular lesions. Lesions on the extremities are slightly larger. (Courtesy Dr. Roger H. Brodkin, Division of Dermatology, CMDNJ-New Jersey Medical School, Newark, NJ.) Fig. 7. Small plaque parapsoriasis (digitate dermatosis): Lesions similar to those of Fig. 6 but elongated and in a palisaded array.

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Figs. 8-13, For legends, see opposite page.

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are absent but the parakeratosis and perivascular infiltrate are prominent, with mild to moderate acanthosis of the epidermis also present. The inflammatory infiltrate does not tend to obscure the dermoepidermal junction in the chronic form. In approximately one fourth of biopsies (Fig. 15) of acute pityriasis lichenoides, and in some biopsies of chronic pityriasis lichenoides, 10% or more of the lymphocytes and histiocytes in the infiltrate are cytologically atypical. 1.2.1a,ao-a.~Such cases are termed lymphomatoid papulosis. Although they almost never show other evidence of malignancy, at least six cases have been reported to progress to a l y m p h o m a (References 34-39, reviewed in Reference 33). The histologic picture in all types of small plaque parapsoriasis is not diagnostic and consists of minimal hyperkeratosis, spongiosis, and acanthosis, with parakeratosis only occasionally present over edematous dermal papillae (Fig. 16). In the papillary dermis, focal, well-defined edema and a sparse perivascular inflammatory infiltrate consisting of lymphocytes, histiocytes, and rare mast cells, with no plasma cells or atypical lymphocytes, is present. Occasionally, a few lymphocytes may be present in nests in the epidermis; these are of bland cytology, distinguishing these nests from Pautrier microabscesses, in which atypical cells are found. Histologically, large plaque parapsoriasis may appear identical to small plaque parapsoriasis

(Fig. 17) or, usually in the more atrophic lesions, may show more characteristic changes consisting of epidermal alrophy and a bandlike to multifocal inflammatory infiltrate containing mostly lymphohistiocytic cells, none to many of which may show cytologic atypia (Fig. 18). These may obscure the dermoepidermal interface and may be present singly or in small groups in the epidermis. The cells in the epidermis are more likely to display cytologic atypia and are usually surrounded by a clear space. Liquefaction degeneration of the stratum basale with pigment incontinence and dilatation of superficial blood vessels (telangiectasis) are often seen, especially in retiform parapsoriasis and in the more severely atrophic lesions of large plaque parapsoriasis (Fig. 19). All of the parapsoriases tend to respond poorly to treatment, which is described in our separate reviews ~'2 and in that o f Nigra and Soter. 13 All tend to persist for varying lengths of time. The premalignant potential is very variable, however. No case of any type of small plaque parapsoriasis that progressed to either a potentially malignant parapsoriasis or to a cutaneous lymphoma of any type could be found by one of us (W. C. L.) in an exhaustive review of the literature. ~ With the exception of the very rare cases of lymphomatoid papulosis that have been reported to progress to lymphoma, pityriasis lichenoides is not known to progress to malignancy. Large plaque parapsoriasis has a very significant incidence of progressing

Fig. 8. Small plaque parapsoriasis: Lesions similar to those of Figs. 6 and 7 but of yellowish color. Such cases have been called xanthoerythrodermia perstans, but do not satisfy the definition of that disease unless they also show palisading. These lesions are larger than usual, but otherwise fit the criteria for small plaque parapsoriasis, illustrating the importance of using all available criteria for distinguishing between large and small plaque disease. Fig. 9. Large plaque parapsoriasis: Large, irregularly shaped, poorly defined lesions on the buttocks. (Courtesy Dr. Joseph B. Bikowski, Sewickley, PA.) Fig. 10. Large plaque parapsoriasis: Poorly defined, mostly large, atrophic lesions over the buttocks. Fig. 11. Large plaque parapsoriasis: Close-up view of a large lesion showing atrophy, telangiectasis, and a very poorly defined border. Fig. 12. Large plaque parapsoriasis (retiform parapsoriasis): Atrophic lesions in a widespread, netlike distribution. (Courtesy Dr. Roger H. Brodkin, Newark, NJ.) Fig. 13. Large plaque parapsoriasis (retiform parapsoriasis): Detail of retiform involvement. The lesion just below the lower left corner of the drawn figure is a biopsy wound.

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Table II. Nomenclature of the parapsoriases Disease entity

Pityriasis lichenoides Acutei"

Chronict

Small plaque parapsoriasis:l:w

Variant: Digitate dermatosis82 Variant: Xanthoerythrodermia perstans82

Equivalent terms in current use*

***Parapsoriasis guttata* + Pityriasis lichenoides et variolifomais acuta + PLEVA + PLVA + Mucha-Habermann disease Parapsoriasis lichenoides et varioliformis acuta Parapsoriasis varioliformis Parapsoriasis acuta* Acute guttate parapsoriasis Acute pityriasis lichenoides +Pityriasis lichenoides chronica* Parapsoriasis lichenoides chronica* Dermatitis psoriasiformis nodularis Chronic guttate parapsoriasis Parapsoriasis en plaques,II small plaque type Parapsoriasis en plaques,II simple discrete type Parapsoriasis en plaques,II benign type Leopard spot parapsoriasis82 ***Chronic superficial dermatitis *** Parapsoriasis guttata* ***Parapsoriasis en plaquesw Fingerprint parapsoriasis82

+ : Preferred synonyms, based on frequent usage. ***: These terms are frequently used by different authors to denote completely different disease entities. *Where obviously equivalent terms in several languages are in common use, only the Latin name is given. Examples are parapsoriasis guttata (guttate parapsoriasis, parapsoriasis en gouttes, - - e n gotas), parapsoriasis liehenoides (lichenoid parapsoriasis, parapsoriasis lichenoide), and parapsoriasis variegata (variegate parapsoriasis). "l'Some authors regard acute and chronic pityriasis tichenoides as separate entities. :[:Some authors consider large plaque and small plaque parapsoriasis as a single entity, usually termed "parapsoriasis en plaques." w term "Brocq's disease" is sometimes used to denote small and large plaque parapsoriasis together as a single entity; less commonly it is also used to denote one or more o f the other parapsofiases. []"Parapsoriasis en plaques" is pronounced with the final " s " silent, misleading some English-speaking authors to misspell it "parapsoriasis en plaque." 82 authors regard digitate dermatosis, of which fingerprint parapsoriasis is a synonym and xanthoerythrodermia perstans a variant, as a separate entity. **Xanthoerythrodermia perstans is digitate dermatosis in which the lesions are yellow in color on clinical examination. It is sometimes incorrectly used to denote cases of other parapsoriases with yellow lesions. t'l'Some authors regard retiform parapsoriasis as a separate entity.

to a cutaneous lymphoma, however, particularly to mycosis fungoides; approximately 10% of patients with large plaque parapsoriasis later develop a lymphoma. Retiform parapsoriasis, moreover, which is fortunately quite rare, has a much higher incidence of malignancy, perhaps approaching 100%, but the number of cases reported is too small to be certain. It is clear that cases of large plaque parapsoriasis that resemble retiform parapsoriasis, particularly regarding widespread epi-

dermal alrophy, have an increased likelihood, perhaps 20%, of developing lymphoma. It is also clear, however, that a few cases of large plaque parapsoriasis develop into lymphomas without ever passing through an atrophic stage. 1 IV. CURRENT NOMENCLATURE; NOSOLOGIC CONTROVERSIES As noted above, there are four major areas of controversy regarding the nosology of parapsoria-

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Table II. Cont'd Disease entity

. . ., . .

Large plaque parapsoriasis~:w

Variant: Retiform parapsoriasistt

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t e r m s in c u r r e n t

use*

+ Atrophic parapsoriasis + Poikilodermatous parapsoriasis Parapsoriasis en plaques,I] large plaque type Parapsoriasis en plaques,II atropfiic type Parapsoriasis en grandes plaques simples Parapsoriasis en grandes plaques poikiloderrniques Lichenoid stage of mycosis ftmgoides Poikilodermic mycosis fungoides Prereticulotic dermatitis Prereticulotic poikiloderma ***Parapsoriasis en plaquesw ***Poikiloderma vasculare atrophicans ***Parapsoriasis lichenoides* + parapsoriasis variegata* + Parakeratosis variegata Lichen variegatus ***Parapsoriasis lichenoides*

sis. The first is whether certain of them may actually represent early stages of a cutaneous lymphoma; it will be dealt with in the final section regarding the relationship of these disorders to malignant disease. The other three areas, which of the parapsoriases are in fact separate entities, which term is most appropriate for each entity, and the use of identical terms ("ambiguous terms") by different authors to denote different diseases, will now be discussed. A. Which of the parapsoriases are distinct entities?

There are five controversies in this group; they will now be discussed in turn. 1. Is parapsoriasis en plaques a single entity oi are there two entities, large plaque parapsoriasis and small plaque parapsoriasis? Although Brocq originally described parapsoriasis en plaques as a single entity, he noted at the outset that there were certain distinguishing features in those cases destined to become malignant. These were, for Brocq, the development of pruritus or of induration or both. 40 The separation of small plaque from large plaque disease was suggested by Degos, ':~ definitively proposed by Palmer, '-'s and has subsequently been accepted and refined by a series of more recent authors, '''4~-4~

although a very few authors still consider parapsoriasis en plaques a single entity encompassing both of the above as variants.4~.47 O f particular relevance, we believe, is the fact that those authors with the largest and the m o s t carefully studied series "8'43-4z'48 are in a g r e e m e n t that these are two entirely separate entities, and, on the basis of this, plus our own experience, we therefore consider the question essentially resolved in favor of this point of view. If one adopts the opposite point of view, however, he or she is immediately in a nosologic quandary, since the only n a m e for this "entity" is parapsoriasis en plaques, a term which has been used by some authors w h o believe there are two diseases to denote exclusively small plaque parapsoriasis 4a and by others to denote exclusively large plaque parapsoriasis. 'i'',~~ Communicating with physicians w h o believe that "parapsoriasis en plaques" is a single entity may therefore be somewhat difficult, but since they appear to represent an ever-dinainishing minority, this problem may soon cease to exist. In those cases (which we believe should be quite unusual) in which one is unable to determine whether a case in question is one of small plaque or of large plaque disease, however, we feel that the term "parapsoriasis en plaques, type not d e t e r m i n e d " is acceptable and unambiguous.

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T a b l e III. Major characteristics of the parapsoriases Type

Pityriasis lichenoides Acute

Chronic

Small plaque parapsoriasis

Variant: Digitate dermatosis Large plaque parapsoriasis

Variant: Retiform parapsoriasis

Clinical features

Generalized erythematous or brown, often necrotic, vesicular or hemorrhagic, scaling papules which are at different stages of evolution; the lesions may recur in acute exacerbations Lesions as above but much less severe, less variable, sometimes more scaly Nonindurated, red-blue to yellow scaling plaques with distinct, regular borders that occur mainly on the trunk; most are <5 cm in diameter Same but lesions are in a palisaded array Slightly indurated, red-blue, scaly plaques with indistinct, irregular borders that occur mainly on the buttocks, proximal extremities, and, in women, the breasts; most are > l0 cm in diameter; atrophy is often present Generalized netlike distribution of red to brown, shiny, fiattopped scaly papules; atrophy is usually prominent

2. Should pit3'riasis lichetzoides be classified within the parapsoriasis group? On the basis of clinical findings inconsistent with Brocq's original criteria ~u,'-'l-'-'a and of histologic features differing from those of the other diseases grouped within parapsoriasis,Z4-'-'~ current authors have removed pityriasis lichenoides fi'om parapsoriasis. Ia This separation has been reinforced by the studies o f Clayton et al, :'~ which provide evidence (deposition of IgM and C3 in blood vessel walls, presence of circulating immune complexes) that pityriasis lichenoides is a

l

Histopathology

.

Broad areas of parakeratosis, focal epidermal necrosis, dilatation and hemorrhage of small blood vessels in the papillary dermis, a wedge-shaped lymphohistiocytic inflammatory infiltrate; atypical lymphocytes may be present Similar to the above but milder and without necrosis or atypical cells in most cases Not diagnostic, but some features may be helpful in differential diagnosis

Prognosis

Lesions clear spontaneously after weeks to months, leaving scars

Individual lesions last for weeks, entire process for years Persists for years to decades with no progression to malignancy

Same

Same

Early, not diagnostic; later atypical large lymphocytes, "mycosis fungoides cells," may appear, particularly in the epidermis

Persists for years to decades; about 10% progress to cutaneous lymphoma

Similar to large plaque parapsoriasis with atrophic changes more prominent

Persists for years to decades; most cases may progress to cutaneous lymphoma

form of immune complex vasculitis. Since the grouping of all diseases within parapsoriasis is essentially arbitrary, it would appear to be of little consequence whether one considers pityriasis lichenoides within it. Samman 2r pointed out, however, that this splitting off of pityriasis lichenoides from parapsoriasis may be unwise, since several cases have been reported in patients with large plaque or retiform parapsoriasis (cases reviewed in Reference 27). Since his report, confirmation of this finding has come from other authors. 14 Also, whereas some disorders grouped

volume 5 Number 4 October, 1981

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385

Fig. 14. Pityriasis lichenoides: Acute vacuolar interface dermatitis with focal necrosis of basal keratinocytes. Epidermal parakeratosis and lymphocytic exocytosis are prominent. Accumulation of lymphocytes, histiocytes, and hemorrhage sun'ounding superficial vessels.

Fig. 15. Pityriasis lichenoides: Lymphomatoid papulosis. Similar to Fig. 6, with an extensive deep intiltrate and a perivascular infiltrate of atypical mononuclear cells. within parapsoriasis may, in contrast to pityriasis lichenoides, progress to a cutaneous lymphoma, certain cases that otherwise resemble acute or chronic pityriasis lichenoides may contain many atypical inflammatory cells--the so-called lymphomatoid impulosis, ao-:~:~and a small number of

these have been reported to progress to a lymphoma. :~4-a:~Thus the relationship, if any, between pityriasis lichenoides and these other diseases remains an interesting and biologically relevant problem; it should not, however, obfuscate communication between physicians of opposing view-

386

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Journal of the American Academyof Dermatology

Fig. 16. Small plaque parapsoriasis (digitate dermatosis): Nondiagnostic changes. Slight acanthosis and spongiotic edema of epidermis with or without hyperkeratosis. Slight lymphocytic infiltrate around vessels of superficial plexus.

Fig. 17. Large plaque parapsoriasis: Nondiagnostic changes. Slight spongiosis with minireal exocytosis. Slight upper dermal perivascular lymphocytic infiltrate. points on this issue, nor should it lead to confusion on the part of physicians who have not yet formulated an opinion. 3. Is piO, riasis lichenoides a single entio,, or are there two entities, piO,riasis lic'henoides et variol(fbrmis acuta and piO'riasis lichenoides chrot~ica? This is a continuing controversy, and it is perhaps significant that one of us (W. C. L.) separated this entity into two diseases, as above, in his

previous review. 1 We do not view this problem as of great importance. The development of this issue and its current resolution--to the extent that resolution has been obtained--have already been reviewed under "Historical Development" (vide slq)ra, section II). In addition, the ulceronecrotic vmiant of pityriasis lichenoides ~2,:''~ is probably an acute form that is more severe or that has a more severe involvement of blood vessels. 4. Is reti/'orm tmrapsoriasis an el~tiO, sui ge-

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387

Fig. 18. Large plaque parapsoriasis: Atrophic type. Hyperkeratosis with atrophy and vacuolar interface dermatitis with lymphocytic exocytosis. Fibrous expansion of the papillary dermis with an extensive, predominantly lymphocytic infiltrate.

U ,

.

.-..:.: ,(,~. ' . ~ .

~*~

.~:

Fig. 19. Large plaque parapsoriasis: Focal infiltration of exocytotic lymphocytes with possible incipient Pautrier microabscess formation. Vacuolar interface dermatitis. Fibrous expansion and lymphocytic infiltrate in the papillary dermis. (This patient developed mycosis fungoides 4 years later.) neris or is it a variant of large plaque parapso-

riasis? The numbers of cases of retiforl-n parapsoriasis reported have been so small that it is difficult to grasp the details of its distinguishing features. 1 Indeed, some authors, who fortuitously have ap-

patently not encountered a case even at certain rather large centers, have doubted its e x i s t e n c e : 4 Where the process has been described, however, it has been attributed a striking presentation that is like that of no other disease entity. "a This is consistent with our own experience; however, we have

388

Lambert and Everett

Table IV. Alternative meanings of ambiguous::: terms

Chronic superficial dermatitis

Parapsoriasis en plaques (unmodified)

Parapsoriasis guttata

Parapsoriasis lichenoides

Poikiloderma vasculare atrophicans

Small plaque parapsoriasis Seborrheic dermatitis (variant) Possibly, nonatrophic large plaque parapsoriasis ? Separate entity Both small and large plaque parapsoriasis (together) Small plaque parapsoriasis (only) Large plaque parapsoriasis (only) Pityriasis lichenoides Chronic pityriasis lichenoides Small plaque parapsoriasis Large plaque parapsoriasis and retiform parapsoriasis together Retiform parapsoriasis (only) Large plaque parapsoriasis (without retiform parapsoriasis) Large plaque parapsoriasis and retiform parapsoriasis together A syndrome which may occur in a number of dermatoses, including dermatomyositis, lupus erythematosus, scleroderma, atrophic lichen planus, xeroderma pigmentosum, and poikiloderma congenitale (Rothmund and Thomson syndromes)

*These temls are ambiguous because they are used by different authors to denote entirely different diseases.

also observed cases showing the changes of retiform parapsoriasis as well as those of large plaque parapsoriasis. We therefore have classified it as a variant of large plaque parapsoriasis. Whether one considers it a separate entity with a high likelihood of progressing to a lymphoma, or a variant of large plaque parapsoriasis which, due to its extensive atrophy, has a similarly high likelihood of under-

Journal of the American Academy of Dermatology

going such malignant degeneration is a question of no significant practical import. Furthermore, physicians with opposite opinions on this question should have no difficulty in communicating. Thus, the nosologic questions surrounding retiform parapsoriasis have theoretical and scientific relevance but at our current level of understanding are of little practical importance. Most importantly, they need not obfuscate communication or understanding of this process. 5. Is digitate dermatosis an entit3, sui generis o1 is it a variant of small plaque parapsoricwis? The original description of this process by Radcliffe-Crocker in 1905 has been discussed under "Historical Development" (vide supra). In 1973, Hu and Winkelmann ~ defined a new entity that they titled "digitate dermatosis," which they distinguished from small plaque parapsoriasis on the basis of its symmetric distribution and palisaded arrangement. They accepted Radcliffe-Crocker's xanthoerythrodermia perstans ~~as a yellowish variant, the first description of their disorder. Since digitate dermatosis has an identical course, prognosis, histology, and management as that of slnall plaque parapsoriasis, we have considered it as a variant of that disorder in this review. Again, biologic questions are interesting but the practical importance of this distinction is at present insignificant.

B. Which term is most appropriate for each entity? Due to the long-standing confusion regarding the nomenclature of this group of diseases, an uncommonly large number of synonyms has arisen for each entity. Those in current use are listed in Table II. Those terms that have been used by different authors to denote entirely different diseases have been so designated in the table and will be discussed under "Ambiguous T e r m s " (vide i1~a, section IV, C). The synonyms for pityriasis lichenoides are either essentially descriptive or eponymic and are thus straightforward. Note that most synonyms refer only to the chronic or the acute form with the intent of designating one or the other as a separate entity. The term dermatitis psoriasiformis nodu-

Volume 5 Numbcr 4 October, 1981

laris has not appeared in the English language literature for some time but is in current use in the European (especially German) literature. The synonyms for small plaque parapsoriasis are, in general, descriptive. Digitate dermatosis, together with xanthoerythrodermia perstans and some or ,all cases of fingerprint parapsoriasis, is actually a variant of the disease as discussed above. The descriptive terms used to denote small plaque and large plaque parapsoriasis center on a number of different characteristics, such as color, size, atrophy, etc., with the chief goal of distinguishing between these two entities. One of us (W. C. L.) prefers terminology based on plaque morphology, 'vJ,4~,4"-,44 originally proposed by Degos, '-':~ which is a distinguishing characteristic given great weight, with few exceptions, 4a'57 even by those who choose not to use this terminology. 4a..ta,48.~ Regarding the use of other descriptive titles, it should be kept in mind that although color and the presence or absence of atrophy are useful signs to distinguish large plaque from small plaque parapsoriasis, both classical large plaque and retiform parapsoriasis may show, at some point, "benign" color, ~'58's'~ and atrophic changes sometimes appear late, "a'~~ or do not appear at all 44'6'-''~a in large plaque parapsoriasis, even when it is progressing toward a lymphoma. Regarding the synonyms for retiform parapsoriasis, this name is preferred simply because it is a better descriptive term than the others. Historical precedent belongs to parakeratosis variegata, proposed by Unna et al in 1890, 3 the first of the parapsoriases to have been described.

C. A m b i g u o u s t e r m s A number of terms have been used by different authors to denote entirely different diseases and are therefore ambiguous. Use of these terms, sometimes by communicating physicians who are not aware that they are actually discussing different diseases, is responsible for much of the confusion surrounding the nosology of parapsoriasis. Whereas some of them (e.g., parapsoriasis en plaques [unmodified]) have different meanings in different countries, others (e.g., parapsoriasis guttata) are routinely used with completely differ-

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ent meanings at major medical centers within the same borough of New York. It is our strong recommendation that these terms be discarded. They are listed in Table II and their various meanings are given in Table IV. Each is now discussed in turn. 1. Chronic superficial dermatitis. McCarthy, in 1942, ~7 called attention to a process, which he considered a variant of seborrheic dermatitis, consisting of well-demarcated, large (palm-sized), oval (never irregularly shaped), scaly, superficial plaques present for the most part over the extremities. Histologically, there was a psoriasiform dermatitis with a markedly parakeratotic stratum corneum. He considered the differential diagnosis of this entity from parapsoriasis en plaques extremely difficult, but suggested that its histology and more favorable response to treatment usually allowed a diagnosis to be made. In 1956, Calnan and Meara c~4 described a similar entity to which they gave the name "chronic superficial dermatitis," suggested to them by Dowling. They did not define the size of their lesions, but differentiated them from small digitate lesions on the trunk and from xanthoerythrodermia perstans, both lesions of small plaque parapsoriasis. They described a similar histology to that of McCarthy, but found that their lesions were fixed and almost completely unresponsive to local therapy. Osmundsenfl a in 1968, considered such lesions to be a form of dermatitis, responsive to topical therapy; he found no example of chronic superficial dermatitis, as defined by Calnan and Meara, in his large clinical survey. Some cases of "chronic superficial dermatitis" would appear to be cases of small plaque parapsoriasis, 4:3some are probably one or another type of dermatitis more or less responsive to current therapy (especially to such treatment as steroids, unavailable in the past), and some may be patients with large plaque parapsoriasis who do not show atrophic changes. 44 It is possible also that chronic superficial dermatitis may exist as a disease sui generis, but if so, it has not yet been adequately defined or reported. The common recent usage of "chronic superficial dermatitis" to denote small plaque parapsoriasis 4a,'i4,ar,~a thus should be

390

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Lambert and Everett

Table V. Incidence of progression of large plaque parapsoriasis to malignancy Malignancy

Series

Bonvalet et al~ Samman4-~ Binazzi et al4-~.48 Osmundsen~-~

Number

of cases

50 40 21 18 129

avoided because both the original definition ~4 and some authors' current interpretation ~6 of this term are clearly inconsistent with this meaning. Possibly Calnan and Meara's ~4 description was of small plaque parapsoriasis exclusive of digitate dermatosis, but their description was insufficiently rigorous to be certain of this. 2. Parapsoriasis en plaques (unmodified). Although this term was among the first used to designate large plaque and small plaque parapsoriasis together as a single entity, 'a,~~ more recent attempts to reserve the term exclusively to denote one or the other disease have led to its use as a synonym for small plaque parapsoriasis in Britain 4n and for large plaque parapsoriasis in the United States. 4~j,5~In addition, it continues to be the term of choice to denote both diseases together used by those who still believe that they should be thus classified. 4n,47 Thus, although the term may be used with modifiers as in Table II with explicit meanings, it should not be used alone. 3. Parapsoriasis guttata. Historically, the first use of this term was by Brocq to designate pityriasis lichenoides. '~ Subsequently, it was used by Ingram 23 to denote small plaque parapsoriasis. More recently, it has been widely used to denote pityriasis lichenoides, 41'4-~,4~,'~~ which it describes somewhat more closely, although some authors have continued to use it as proposed by Ingrain. 2a,~0,6:~ 4. Parapsoriasis liehenoides. In addition to being easily confused with the term pityriasis lichenoides, which has an entirely different meaning, this term has been used by some authors to denote retiform parapsoriasis only and by others to denote large plaque parapsoriasis including retiform parapsoriasis within it. "z,'a.41,4a,44

Duration followed

5-64 8-20 + 1-20 6-37

(yr)

.L-..-._

Number

I

%

6 3 3 2

12.0 7.5 14.3 I1.1

14

10.9

5. Poikiloderma vasculare atrophicans. Poikiloderma vasculare atrophicans is not a disease entity, but rather is a syndrome occun'ing in one or another stage of a number of quite different dermatoses41'42"~",6:~,7~ the original cases reported, from Europe, 71,7' were patients with dermatomyositis, although it is true that the first American patient developed a cutaneous lymphoma. 7.~a.~The syndrome consists of: (1) mottled hyperpigmentation and hypopigmentation (poikilo-), (2) telangiectasis (vasculare), and (3) progressive atrophy (atrophicans) of the skin (-derma). Histologically, the corresponding alterations are dermal and, particularly, epidermal atrophy, sometimes with hyperkeratosis and liquefactive degeneration of the basal zone, incontinence of melanin into the dermis, and dilation of small superficial blood vessels, with a very variable perivascular and/or bandlike lymphohistiocytic infiltrate. In modern usage, the clinical term "poikiloderma" alone has come to denote the entire process, 61 all three elements of which are required. There are, however, a large number of conditions in which only two or even one of these changes is usually seen (e.g., Bloom's syndrome, acrodermatitis chronica atrophicans); such cases should not be considered examples of poikiloderma, but are often incorrectly designated as such. ~'~ Poikiloderma fairly commonly follows acute or, more frequently, prolonged topical exposure to a variety of physical and chemical agents, particularly several types of radiation (including sunlightr'~; thermal insult, especially cold76; and polycyclic hydrocarbons, such as those in oil, pitch, and tar77). It may also occur in association with a number of otherwise manifest dermatoses, particularly mycosis fungoides and large plaque

Volume 5 Number 4 October, 1981

parapsoriasis, and may follow a number of inflammatory conditions, such as lichen planus. 4'~ The term poikiloderma vasculare atrophicans should be reserved for those rather rare cases in which the gradual onset of more or less widespread, symmetric poikiloderma is the only, or principal, skin manifestation of the disease process.',78 Usually, there is either (1) an occult lymphoma, particularly mycosis fungoides, (2) large plaque parapsoriasis, 4''~l'~'''r~ (3) an underlying dermatomyositis, "poikilodermatomyositis, ''7:).~~ or (4) less frequently, another connective tissue disease, particularly lupus erythematosus 81 or scleroderma, "poikiloscleroderma,"c;:~'8' as the cause of the syndrome. Other causes include a number of genodermatoses (reviewed in Reference 82), particularly xeroderma pigmentosum and poikiloderma congenitale (Rothmund and Thomson syndromes), and certain ingested substances, such as arsenic compounds (arsphenamine, neoarsphenamineTa). Almost all cases will be found to have an underlying cause, although a very few apparently idiopathic cases have been reported. 7~,8,.sa Thus, although both large plaque parapsoriasis and its variant, retiform parapsoriasis, may present as the syndrome "poikiloderma vasculare atrophicans," the term "poikiloderma vasculare atrophicans"aa should not be used to denote either or both of them.

D. Relationship between parapsoriasis and cutaneous l y m p h o m a Recently, some authors have reclassified both classical large plaque and retiform parapsoriasis as representing early stages of cutaneous lymphoma, rather than as one or more diseases sui generis.~a Although aware that not all cases of either disease progress to lymphoma, even if followed for many years, Samman ~'~'~'~4 argued that this fact is consistent with this reclassification if one assumes a sufficiently gradual progression of the lymphoma. This and the question of the chance of neoplastic degeneration are clearly the most important clinical issues regarding parapsoriasis; therefore, we shall examine them in some detail: 1. Do large plaque parapsoriasis and retiform parapsoriasis represent one or more disorders sui

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391

generis or are they early stages of cutaneous lymphoma? 2. What are the chances of a patient with large plaque or retiform parapsoriasis developing a lymphoma? While large plaque parapsoriasis may indeed progress to a cutaneous lymphoma, this progress often requires many years, is often accompanied by prior changes in the morphology of the lesions, and does not occur in a large proportion of cases. Table V shows the numbers of cases that underwent such a progression in the largest and, we believe, most carefully studied series available. Note that the incidence both overall and in each study considered alone is only about 10%. Review of the literature as a whole shows wide variations, but considering it in aggregate, the incidence of this development is again approximately 100~. 18.21,23,28,43,45,48,57,62,133,65 Considering the problem from the opposite perspective, the number of cases of overt cutaneous lymphoma that were known to be preceded by any of the parapsoriases or by poikiloderma or alopecia mucinosa was found by Green et al, ~s analyzing data from the Mycosis Fungoides Cooperative Study Group 86 and from a carefully administered county-bycounty retrospective study of cancer mortality conducted by the National Cancer Institute, 87 to be only 16%. The overall incidence of prior noninfectious skin diseases in these patients, moreover, was 77%. 8a Thus the statistical correlation between the parapsoriases and lymphoma, although important, seems to us insufficient, in light of the present limited understanding of the underlying mechanisms of these diseases, to justify lumping one or more of them together with lymphoma of any type as a single disease. Recent studies have shown that patients with occupationally related dermatoses and certain types of chronic skin conditions are at a significantly increased risk of developing mycosis fungoidesY ~'88'8' We interpret these findings as follows: It is well known that certain clearly nonneoplastic conditions very markedly predispose patients to cancer in the affected organ. Examples are hepatic cirrhosis and development of hepatocarcinoma and schistosomiasis due to Schistosoma haematobium and development of carcinoma of

Journal of the American Academy of Dermatology

392 Lambert and Everett

the bladder. Such clear-cut relationships between nonneoplastic inflammatory conditions and specific types of cancer are innumerable in human pathology. The classical experiments (principally) of Dr. Michael Potter, in which injections of mineral oil and purified mineral oil extracts into the peritoneal cavity of BALB/c mice consistently result in development of plasmacytomas (References 90 and 91, reviewed in Reference 92) indicate that immunocompetent cells (plasmacytomas are derived from B lymphocytes) are similarly susceptible to malignant transformation by a chronic irritating stimulus or inflammatory process. Similar results have also been obtained with other animal lymphomas following protracted, severe immunologic stimulation.'J3 These results are further corroborated by the finding, in humans, that chronic inflammatory bowel disease predisposes patients to development of multiple myeloma (Reference 94, reviewed in Reference 95) and malaria to development of Burkitt's lymphoma, 96 indicating that human immunocompetent cells are similarly susceptible to this type of carcinogenesis. Patients with long-standing occupational dermatoses, in which their immunocompetent cells are chronically stimulated by the same antigens, would thus develop lymphoma as a secondary event. In an entirely analogous manner, patients with large plaque parapsoriasis might eventually develop lymphoma, but this should not necessarily be construed to indicate that they were affected with an early form of lyrnphoma from the beginning. Nor should the fact that the progression from large plaque parapsoriasis to lymphoma is gradual and virtually imperceptible be interpreted as evidence that large plaque parapsoriasis is a form of lymphoma; a similar gradual progression occurs from the occupational dermatoses to lyrnphoma. Since there is also a high incidence (greater than 61%) of a prior inflammatory dermatosis other than a parapsoriasis in patients who develop mycosis fungoides, 8~ it would appear that other inflammatory conditions may also predispose patients to development of lymphoma, although perhaps less commonly than large plaque parapsoriasis. It is noteworthy that Green et al, s~ Tan et al, a7 and Cohen et al, 89 studying the prob-

lem from the opposite perspective, that of patients who already have mycosis fungoides, came to conclusions more or less similar to those expressed here. In the future, it may be possible to distinguish which cases of large plaque parapsoriasis, of retiform parapsoriasis, or of lymphomatoid papulosis are progressing toward malignant disease, and it would be unfortunate if a large population of patients were then found to have been inappropriately given a diagnosis of cutaneous lymphoma. Van Vloten et a198 found that, by plotting histograms of DNA content of mononuclear cells in a number of infiltrative skin disorders, abnormal patterns of cellular DNA content can in some diseases be identified. They found that cases of "parapsoriasis" with normal DNA monocyte histograms do not progress to a lymphoma, whereas those with abnormal patterns usually do. Another current approach is the use of hybridoma-derived monoclonal antibodies to identify cell types and subtypes in biopsy specimens.9'~)These are promising technics which, integrated with carefully constructed large scale clinical studies, should provide very interesting data in the near future. REFERENCES

1. Lambert WC: Parapsoriasis, in Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austin KF, editors: Dermatology in general medicine, ed. 2. New York, 1979, McGraw-Hill Book Co., pp. 808-817. 2. Everett MA, Headington JT: Parapsoriasis, in Demis DJ, Dobson RL, McGuire JS: Clinical dermatology. Hagerstown, MD, 1979, Harper & Row, Publishers, Inc., sect. 1-6, pp. 1-18. 3. Unna [PG], Santi, Pollitzer: Uber die Parakeratosen im Allegcmeinen und eine neue Form derselben (Parakeratosis variegata). Monatschr Praktische Dermatol 10: 404-412, 1890. 4. Neisser A: Zur Frage der lichenoiden Eruptionen. Verh Dtsch Dermatol Ges 4:495-506, 1894. 5. Jadassohn J: Ueber ein eigenartiges psoriasiformes und lichenoides Exanthem. Verh Dtsch Dermatol Ges 4: 524-535, 1894. 6. Juliusberg F: Ueber die Pityriasis lichenoides chronica (psoriasiform lichenoides Exanthem). Arch Dermatol Syph (Wien) 50;359-374, 1899. 7. Brocq L: Les 6rythrodermies pityriasques en plaques diss~min~es. Rev Gen J Practiciens 11:577-590, 1897. 8. Fox TC, Macleod JMH: On a case of parakeratosis variegata. Br J Derrnatol 13:319-346, 1901. 9. Brocq L: Les parapsoriasis. Ann Dermatol Syphiligr (Paris) 3:433-468, 1902.

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10. Radcliffe-Crocker H: Xanthoerythrodermia perstans. Br J Dermatol 17:119-134, 1905. 11. Mucha V: Ober einen der Parakeratosis variegata (Unna) bzw. Pityriasis lichenoides chronica (Neisser-Juliusberg) nahestehenden eigentumlichen Fall. Arch Dermatol Syph (Wien) 123:586-592, 1916. 12. Habermann R: 0ber die akut vereaufendc, nekrotisierende Unterart der Pityriasis lichenoides (Pityriasis lichenoides ct varioloformis acuta). Dermatol Z 45:42-48, 1925. 13. Nigra TP, Soter NA: Pityriasis lichenoides, i~1 Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg IM, Austen KF, editors: Dermatology in general medicine, ed. 2. New York, 1979, McGraw-Hill Book Co., pp. 665-668. 14. de Dulanto F, Sierra JO, Pertinez RC : Parapsoriasis en gotas y varioliforme. Actas Dermosifiliogr 62:377-390, 1971. 15. Marks R, Black M, Wilson Jones E: Pityriasis lichenoides: A reappraisal. Br J Dermatol 86:215-225, 1972. 16. Wise F: Parapsoriasis, suggestions for simplifying its nomenclature and classifying its clinical varieties for teaching purposes. NY State J Med 28:901-908, 1928. 17. McCarthy L: Differential diagnosis ofparapsoriasis. Arch Dermatol Syph 45:81-102, 1942. 18. Keil H: Parapsoriasis en plaques diss6minges and incipient mycosis fungoides. Arch Dermatol Syph 37:465494, 1938. 19. Sutton RL: Diseases of the skin. St. Louis, 1956, The C. V. Mosby Co., pp. 936-941. 20. Wile: Discussion of case presented by Dr. Orrnsby. Arch Dermatol Syph 13:690, 1926. 21. Lapiere S: I~volution et pronostic du parapsoriasis en plaques. Ann Dermatol Syphiligr (Paris) 9:609-622, 1949. 22. Civatte A: Le cinquantenaire du parapsoriasis. Ann Dermatol Syphiligr (Paris) 78:5-22, 1951. 23. Ingram JT: Pityriasis lichenoides and parapsoriasis. Br J Dermatol 65:293-299, 1953. 24. Szymanski FJ: Pityriasis lichenoides et varioliformis acuta, histopathological evidence that it is an entity distinct from parapsoriasis. Arch Derrnatol 79:7-16, 1959. 25. Kruger H: Ober klinische und histologische Beziehungen der allergischen Vasculitis zu bestimmten Formen der Parapsoriasisgruppe. Acta Allergol (Kbh) 14:356-359, 1959. 26. Weise H J: Ober klinische Lind histologische Beziehungen der allergischen Vasculitis zu bestimmten Formen dcr Parapsoriasisgruppe. Acta Allergol (Kbh) 14:360-363, 1959. 27. Samman PD: Poikiloderma with pityriasis lichenoides. Trans St Johns Hosp Derrnatol Soc 57:143-147, 1971. 28. Palmer DD: Atrophic (poikiloderma vasculare atrophicans) and extensive (retiform parapsoriasis) fornas of parapsoriasis. Master of Science thesis, Mayo Graduate School of Medicine, University of Minnesota, 1962. 29. Degos R: Dermatologie. Paris, 1953, Flamarion, pp. 188-194. 30. Macaulay WL: Lymphomatoid papulosis: A continuing self-healing eruption, clinically benign-histologically malignant. Arch Dermatol 97:23-30, 1968.

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31. Valentino LA, Helwig EB: Lymphomatoid papulosis. Arch Pathol 96:409-416, 1973. 32. Thomsen K, Hjort G, Svendsen D: Lymphomatoid papulosis. Dermatologica 144:65-74, 1972. 33. Macaulay WL: Lymphomatoid papulosis. Int J Dermatol 17:204-212, 1978. 34. Kawada A, Anekoji K, Miyamoto M, Nakai T, Mori S: Unusual manifestation of malignant reticulosis of the skin: Cutaneous lesion simulating parapsoriasis guttata. Dermatologica 138:369-378, 1969. 35. Black MM, Wilson Jones E: Lymphomatoid pityriasis lichenoides: a variant with histological features simulating a lymphoma: Br J Dermatol 86:329-347, 1972. 36. Fine RM, Meltzer HD, Rudner EJ: Lymphomatoid papulosis eventuating in mycosis fungoides. South Med J 67:1492-1498, 1975. 37. Dupont A: Langsam verlaufende und klinisch gutartige Reticulopathie mit h6chst maligner histologischer Struktur. Hautzart 16:248-286, 1965. 38. Dupont A: La longue evolution d'une reticulose paptdeuse apparement benigne et sa transformation maligne tardie. Bull Soc Franc Dermatol Syphilol 80:153-160, 1973.

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Journal of the American Academy of Dermatology

74. Lane JE: Poikiloderma atrophicans vasculare: Conclusion of a previously reported case. Arch Dermatol Syph 8:373-381, 1923. 75. Dowling JG, Edelstein JM, Fitzpatrick TB: Poikiloderma vasculare atrophicans, report of a case with observations at autopsy. Arch Dermatol Syph 56:740-762, 1947. 76. Dowling JG, Edelstein JM; Poikiloderma vasculare atrophicans, report of a case due to exposure to cold. Arch Dermatol Syph 62:206-213, 1950. 77. Allison JH: A benign variant of poikiloderma. Trans St Johns Hosp Dermatol Soc 40:54-58, 1958. 78. Watsky MS, Lynnfield YL: Poikiloderma vasculare atrophicans. Cutis 17:938-941, 1976. 79. Janis JF, Winkelmann RK; Histopathology of the skin in dermatomyositis: A histopathological study of 55 cases. Arch Dermatol 97:640-650, 1968. 80. Horn RC: Poikilodermatomyositis: Report of a case with complete postmortem examination. Arch Dermatol Syph 44:1086-1097, 1941. 81. Tuffanelli DL. Levan NE, Dubois EL: Unusual cutaneous disorders in familial lupus erythematosus. Arch Dermatol 89:324-327, 1964. 82. Weary PE, Manley WF, Graham GF: Hereditary acrokeratotic poikiloderma. Arch Dermatol 103:409-422, 1971. 83. Wolf DJ, Selmanowitz V J: Poikiloderma vasculare atrophicans. Cancer 25:682-686, 1970. 84. Samman PD: Chronic superficial dermatitis and poikiloderma. Bull Cancer (Paris) 64:177-186, 1977. 85. Green MH, Dalager NA, Lamberg SI, Argyropoulos CE, Fraumeni JF: Mycosis fungoides: Epidemiologic observations. Cancer Treat Rep 63:597-606, 1979. 86. Lamberg SI, Chairman, Mycosis Fungoides Cooperative Study Group Steering Committee: Mycosis fungoides Cooperative Study. Arch Dermatol 111:456-459, 1975. (Editorial.) 87. United States Bureau of the Census. Alphabetical index of industries and occupations, in U.S. Census of Population 1970. Washington, DC, 1971, U.S. Government Printing Office, pp. vii-xiv. 88. Fischman AB, Bunn PA, Guccione JG, Matthews MJ, Minna JD: Exposure to chemicals, physical agents, and biological agents in mycosis fungoides and the S~zary syndrome. Cancer Treat Rep 63:591-596, 1979. 89. Cohen SR, Stenn KS, Braverman IM: Mycosis fungoides: Clinicopathologic relationships, survival, and therapy in 59 patients with observations on occupation as a new prognostic factor. Cancer 46:2654-2666, 1980. 90. Potter M, Robertson CL: Development of plasma-cell neoplasms in BALB/c mice after intraperitoneal injection of paraffin-oil adjuvant, heat-killed staphylococcus mixtures. J Natl Cancer [nst 25:847-861, 1960. 91. Merwin RM, Algire J: Induction of plasma cell neoplasms and fibrosarcomas in BALB/c mice carrying diffusion chambers. Proc Soc Exp Biol Med 101:437, 1959. 92. Potter M, Pumphrey JG, Bailey DW: Genetics of susceptibility to plasmacytoma induction. I. BALB/c AnN (C), C57BL/6N (B6), C57BL/ka (Bk), (CxB6) F1, (CxBA) F,, and CxB recombinant inbred strains. J Natl Cancer lnst 54:1413-1417, 1975. 93. Schwartz RS, Beldott I: Malignant lymphomas following

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allogeneic disease. Transition from an immunological to a neoplastic disorder. Science 149:1511-1514, 1965. 94. Osserman EF: Plasma cell dyscrasias, in Beeson PB, McDermott W, Wyngaarden JB; Cecil's Textbook of medicine, ed. 15. Philadelphia, 1979, W. B. Saunders Co., pp. 1852-1867. 95. [sobe T, Osserman EF: Pathologic conditions associated with plasma cell dyscrasias: A study of 806 cases. Ann NY Acad Sci 190:507-517, 1971. 96. O'Connor GT: Persistent immunologic stimulation as a factor in oncogenesis, with special reference to Burkitt's tumor. Am J Med 48:279-285, 1970.

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