332

SKIN MANIFESTATIONS OF THE RETICULOSESBy F. RAY BETTLEY, F.R.C.P.

Physician for Diseases of the Skin, The Middlesex Hospital, London

The conception of the reticulo-endothelialsystem belongs to the realm of experimental path-ology. The reticuloses, a group of disordersprimarily affecting that system are, therefore, aconcept of pathology and their clinical manifesta-tions must be diverse. Indeed, even amongpathologists, opinions are divided as to the criteriawhich govern admission to the group. It would bewidely conceded that reticuloses are liable to in-volve cells of the reticulo-endothelial system inwhatever part of the body they occur, and sincethe skin is a very readily observed organ in whichreticulo-endothelial elements are numerous, it isnot surprising that most reticuloses have dermato-logical manifestations-though some much morefrequently than others.At the present time the reticulosis group is made

up of a number of syndromes which in theirdermatological manifestations are characterizedby a massive infiltration of the dermis with cells ofproved or presumed origin from the reticulo-endothelial system. As Goldsmith (I944) pointedout, it would be absurd to make the condition thatthe cause must be unknown, i.e. that no infectiveor similar agent has been identified. At the sametime, it is impossible entirely to escape the notionthat the chronic granulomatous process ofHodgkin's disease is acceptable as a reticulosis,whereas to include the widespread chronic granu-lomatoses of the well-known infections would beto broaden the concept of reticulosis until it losesits meaning. With very few exceptions then, thecauses of the reticuloses are unknown. To theclinician a purely pathological classification is notentirely satisfactory; a purely clinical classificationis still more unsatisfactory since a single entitysuch as mycosis fungoides may produce clinicalmanifestations of great diversity. These mani-festations may be grouped into three classes andit is from this purely clinical aspect that thereticuloses are now considered; such a clinicalclassification cuts across the pathological classifica-tion and is in no way a substitute for it. The threetypes of manifestation referred to are: (I) General-ized pruritus; (2) superficial eruptions; and (3)infiltrated or tumour-like lesions.

Generalized PruritusThe generalized pruritus which occurs in the

reticuloses is most often seen in Hodgkin's disease

and mycosis fungoides, and less often in lymphaticleukaemia. The irritation usually affects equallythe entire skin surface and is at first unaccompaniedby any objective change in the skin. It is a severeitching, sometimes paroxysmal, but seldom re-mitting completely. This severe irritation usuallyleads to violent scratching, and the secondaryeffects of excoriation and lichenification of the skinmay develop after a few weeks. The nails are oftenpolished by their friction against the skin in theact of scratching.During the phase of general pruritus other

manifestations of the reticulosis may not beidentifiable and even biopsy of the skin may showno characteristic changes and give no help indiagnosis. Indeed, the phase of general pruritusoften ceases as the reticulosis evolves, so that bythe time diagnosis is possible, the irritation hasalready disappeared. The differential diagnosis ofgeneralized pruritus may, therefore, be extremelydifficult or impossible. Conditions such asjaundice, senile pruritus, metabolic upsets such asthose associated with uraemia and, of course,parasitic skin diseases must all be excluded.General pruritus of psychiatric origin may bedifficult to distinguish and often, when clinicalexamination reveals no cause and pathological testsgive no help, the nature of this symptom can onlybe recognized after a period of observation duringwhich some other manifestation of the reticulosisdevelops.Superficial Eruptions

In this category are included a wide diversity oferuptions in which the dermis, and often theepidermis, are involved without any notable degreeof infiltration in the lesions. Sometimes aneruption of this kind follows a period of generalpruritus; in other cases a superficial eruptiongradually becomes more infiltrated until it passesinto the third category of tumour-like lesions.

It is in mycosis fungoides that this class of erup-tion is most commonly and most typically seen.The disease often starts with a widespread eruptionaffecting principally the trunk and proximal partsof the limbs. The rash is usually made up of largeerythematous sheets, profusely scaly, itchy andsometimes weeping. In this way eczema andpsoriasis may be simulated for a time. Character-istic of these eruptions, however, is a blotchy

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July 1951 BETTLEY: Skin Manifestations of the Reticuloses 333

brick-red or dusky colour which often gives a clueto diagnosis. Biopsy of the skin may showpathognomonic changes but in other cases givesno help. This stage of erythroderma may be ofshort or of comparatively long duration, occasion-ally lasting for many years before the tumour stageof the disease is reached.

In other cases a widespread or, more often,generalized eczematous eruption, the appearancesof which seem to be typical of eczema or sebor-rhoeic dermatitis, is eventually followed by thedevelopment of a reticulosis (Fig. i). In thesecases, early diagnosis may be particularly difficult,since the eruption is identical in appearance withother cases of eczema or seborrhoeic dermatitiswhich eventually clear up without any sign ofreticulosis.

Exfoliative dermatitis, a result of widespreadeczema, seborrhoeic dermatitis or psoriasis, usuallyloses the characteristics of the original lesion,and whatever their origin, such cases occasionallypass into reticulosis. This is often taken to in-dicate that the skin eruption was really from theoutset a manifestation of the reticulosis; it ispertinent, however, to ask whether reticulosis maynot arise as a consequence of long-standing ery-throderma. Nearly always, in such cases, thereticulosis appears only after the skin changeshave continued for some years, or even decades.These cases should be distinguished from the

so-called lipo-melanic reticulosis (Pautrier andWoringer, 1932), in which a special type of lymph-adenopathy occurs. This lymphadenopathy,characterized by considerable accumulation ofmonocytes and the presence of melanin and fat inthe lymph nodes, may complicate a variety ofwidespread dermatoses. There can be little doubtthat it is really a rather special type of non-specificlymph gland response which disappears once theskin lesions heal. This type of lymphadenopathyshould, therefore, not be classed with the truereticuloses and it is misleading to include it inthis group.

In recent years it has been observed that severaluncommon chronic dermatoses occasionally passon to frank and apparently typical mycosis fun-goides. Parapsoriasis en plaques is a symptomlessextremely chronic eruption made up of well-defined pink macules covered with fine scalingand with only the slightest degree of cellular in-filtration in the dermis either clinically or histo-logically. Both this condition and poikolodermaare sometimes seen to proceed to mycosis fun-goides, though in most cases such an evolutiondoes not occur.

Urticarial eruptions are occasionally seen inother reticuloses; the vesicular leucaemide, con-sisting of a widespread eruption of small isolated

vesicles on a slightly infiltrated base, is a rarecuriosity.

Acquired ichthyosis, or xeroderma, is oc-casionally seen; the whole skin surface becomesdry and is covered with fine adherent scales.Itching is slight or absent. This change in the skinis usually a late manifestation and is often as-sociated with cachexia (Fig. 2). It is presumablymetabolic in origin, since the histology of the skinshows no abnormal cells.

FIG.i.i.Longstanding generalized erythroderma

(Homme Rouge ) The entire surface is scaly and

red. Note the enlargement.... of superficial lymph

glands (Dr H T H Wson..s ..ase.

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334 POSTGRADUATE MEDICAL JOURNAL July 195,

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FIG. 2.-Acquired xeroderma. Section of the midlineof the back in a patient.-with advanced Hodgkin'sdisease.

TumoursTumours and infiltrated lesions are encountered

in all gradations, from a slightly infiltrated plaqueto massive tumours up to the size of a melon. Inmycosis fungoides it is usual for the stage oftumour formation to supervene after a period ofa few years, during which superficial eruptionsappear. Less commonly, however, is seen thetype ac tumeurs d'emblee, in which the formation ofdermic tumours is the first sign of the disease.In either type the tumours are situated in thedermis, starting as deep red or purplish, firmhemispherical swellings about half-an-inch across(Fig. 3). The lesions are usually freely mobileon the subcutaneous tissue and remain so evenwhen they have much increased in size. Theygrow rapidly and often attain a diameter of two orthree inches in the course of a month. By thetime they are this size, the mass often shows somelobulation and resembles a half tomato stuck onthe surface of the skin. The epidermis is at first

stretched tightly over the tumour, but eventuallyulcerates. A good deal of necrosis often results,leaving a deep punched-out ulcer surrounded bya thick rim of tumour tissue. It is a remarkablecharacteristic of these tumours that they mayinvolute spontaneously at any time and heal asrapidly as they appear, with little or no scarring.As the disease progresses, however, more and moretumours develop and the tendency to spontaneousinvolution is reduced until the patient may becovered with as many as 50 ulcerated tumoursvarying up to several inches across (Fig. 4).The development of cutaneous tumours in

Hodgkin's disease is decidedly less common.When they do appear, they are often the first signof the disease, and a meticulous search may revealno other manifestations for a time. In due course,however, the more common manifestations developand the disease runs an otherwise usual course.These tumours often exactly resemble those ofmycosis fungoides in clinical appearance, though

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ruly I951 BETTLEY: Skin Manifestations of the Reticuloses 335

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Fl. 3.--Myosis fungoides. Multiple skin tuous, some showing early ulceration.

FIG. 3. Mycosis fungoides. Multiple skin tumours, some showing early ulceration.

they tend to be somewhat harder, they are fewer,and ulceration is less likely to occur. (Fig. 5).Their situation in the substance of the skin, freelymobile over the subcutaneous tissues, their firm-ness to the touch and reddish or plum colour arecharacteristic. These features and their rapidgrowth usually point to the diagnosis, thoughbiopsy is nearly always necessary for the exactclassification of the disorder. In the early tumourstage the cell picture may be difficult to interpretand it may be that only later on biopsy of a lymphgland permits accurate diagnosis. This is prob-ably the explanation of at least some of thosecases where one reticulosis is said to have beentransformed into another.

Similar tumours may occur in the leukaemias.In these cases the masses may be more diffuse andpresent brawny indurated areas 6 in. or moreacross. The borders of these infiltrated areas maybe ill-defined and, in many respects, the clinicalpicture resembles that of cellulitis; the purplishcolour of the lesion, however, and the completelack of pain make distinction easy.

In sarcoidosis two types of skin nodule may beproduced, both showing the typical histological

structure. The lesions known as lupus pernio areof a deep red or cyanotic hue. They form well-defined firm infiltrated areas, raised a little abovethe surface of the surrounding skin. They tend toremain relatively unchanged for a considerableperiod, usually showing little tendency to enlargeand little tendency to spontaneous healing. Theselesions occur most often about the nose and cheeksand on the fingers. The second type of cutaneoussarcoid takes the form of smaller tumours; these,too, are situated chiefly on the face, ears and handsand consist of brownish raised nodules, sharplyoutlined and usually i or 2 cm. in diameter. Theirdegree of pinkness is variable; if they are examinedthrough a glass slide pressed on the skin so as toexpel the blood, they have a brownish-yellow semi-translucent appearance resembling that of tubercu-lous lupus. While these appearances are clinicallysuggestive of sarcoidosis, the diagnosis must alwaysdepend, as in other reticuloses, on the histologicalpicture and biopsy is always necessary. It should,at the same time, be recalled that the clinical andhistological picture of sarcoidosis may be closelymimicked by other disorders; leprosy may pro-duce very similar lesions, while the granulomata

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336 POSTGRADUATE MEDICAL JOURNAL July i95i.. .... :' .. :".. :,

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FIG. 4.~Mycosis fungoides. Multiple punched outulcers, many of which would heal spontaneouslyafter several weeks. The skin of other parts of thebody, e.g. shoulders, is diffusely red and scaly.

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which form around particles of silica and berylliumin the skin may be distinguishable only by findingthe foreign bodies.The brownish circumscribed tumour of sar-

coidosis may easily be confused on clinical ex-amination with a variety of eosinophilic granuloma.The latter term has been variously used todescribe lesions in the skin and elsewhere. Thelocalized granuloma now under consideration is sonamed because it consists of a mixed cellular in-

filtrate in which eosinophils are very numerous.These cases do not seem to be produced by anylocal agent; at the same time, disseminated lesionsdo not often appear and it is doubtful whether thistype of eosinophilic granuloma should be classifiedwith the reticuloses (Rook, I950).On close inspection of the sarcoid nodule in the

skin it is sometimes possible to distinguish a finestippling of brownish pin-point nodules. In somecases these nodules are more widely separated.

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July I951 BETTLEY' Skint Manifestations of the Reticuloses '337

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FIG. 5.--Primary tumour of Hodgkin's disease in the skin. This firm elevated plaque was followed byother skin lesions and later by typical systemic involvement (see Fairburn, I950)·

thus giving rise to a reddish area, perhaps i or 2cm. across, in which scattered yellow-brownstipples about i mm. or less in diameter arescattered. These miliary sarcoid lesions may bewidely spread on the skin of the trunk and limbs.Other signs of sarcoidosis may be present in thesecases but, nevertheless, the diagnosis must largelydepend on histological examination. In rare caseswith apparently identical skin lesions, biopsyshows a more mixed cellular infiltrate which, evenin the presence of other signs suggestive of sar-coidosis, makes the latter diagnosis unacceptable.The exact classification of this latter type of case isvery difficult and is better based on histologicalexamination of the lymph nodes, if these are in-volved, than on skin biopsy.

Apart from these broad considerations, thereare a few clinical dermatoses which have featuresof their own and which are probably to be con-sidered as reticuloses. Miliary lymphocytoma isone of these (Bettley, I947). This rare syndromepresents a remarkably constant clinical picture ofpinhead size, semi-translucent bluish nodulesscattered on the forehead and upper half of the

face. Irritation usually affects the trunk and limbsas well as the face and the skin is abnormallysensitive to light. Biopsy shows the facial nodulesto be composed of lymphocytic germ centresclosely resembling those found in the lymph nodes.It is very doubtful whether benign lymphocytomaever produces leukaemia or any lesion elsewhere inthe reticulo-endothelial system and, for thisreason, it is thought by some to be nothing morethan a special type of reaction in a person who isabnormally sensitive to light.

Urticaria pigmentosa may be considered in thiscategory; it consists of the widespread develop-ment of well-outlined, pigmented circular and ovalareas, chiefly on the trunk, which are readily con-verted into urticarial wheals on slight trauma.Histologically the lesion contains a remarkablenumber of mast cells and this has led to thesuggestion that urticaria pigmentosa should beclassified as a reticulosis involving elements of themast cell series. By others, however, the disorderis regarded as naevoid in nature.

Figs. 2, 3 4 and 5 were prepared in the Photographic Departmentof the Middlesex Hospital, London.

BIBLIOGRAPHY

BETTLEY, F. R. (I947), Brit. J. Derm., 59, 70.FAIRBURN, E. A. (i950), Ibid., 62, 504.GOLDSMITH, W. N. (1944), Ibid., 56, 107.

PAUTRIER, L-M., and WORINGER, F. (1932), Bull. Soc. franc.Derm., 39, 947.

ROOK, A. J. (I950), Brit. J. Derm., 62, 411.

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