Pathology of Lupus Erythematosus - COnnecting REpositories · PATHOLOGY OF LUPUS ERYTHEMATOSUS HAMILTON MONTGOMERY, M.D.' (Received for publication July 17, 1939) Diagnosis of lupus

PATHOLOGY OF LUPUS ERYTHEMATOSUS

HAMILTON MONTGOMERY, M.D.'

(Received for publication July 17, 1939)

Diagnosis of lupus erythematosus in the present state ofknowledge of the disease must depend chiefly on recognition ofthe cutaneous lesions (33, 40). This is usually easily done intypical cases of the chronic localized discoid type of the disease.But the clinical differential diagnosis of lupus erythematosus.other dermatoses and toxic erythemas may be at times exceed-ingly difficult in certain cases of acute and subacute disseminatetypes of lupus erythematosus. I wish to describe the cardinalcutaneous histolpgic changes seen in cases of lupus erythematosus.I believe that a combination of these changes permits a definitediagnosis to be made (16). Reference to controversial pointsin regard to the diagnostic significance of changes in connectiveand elastic tissue and the various vascular changes will be con-sidered. The differential diagnosis of lupus erythematosus andother dermatoses will be considered and a brief review of thegeneral pathologic changes to be found in various internal organswill be given.

This study is based on the correlation of cutaneous histologicchanges seen in forty cases of the chronic discoid type and inforty cases of the disseminate types of lupus erythematosusincluding thirteen cases in which the disease was of the acutedisseminate type, as compared with the clinical findings in thecourse of the disease in a total of 460 cases of lupus erythematosusseen at The Mayo Clinic. In 154 of these cases the disease wasof the chronic disseminate, subacute or acute disseminate form;these cases have been reported elsewhere (33). It is significant

1 From The Section on Dermatology and Syphilology, The Mayo Clinic,Rochester, Minnesota.

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that in a third of the thirty cases of acute disseminate lupus erythe-matosus the disease started as a chronic localized discoid type oflupus erythematosus and that pathologically all transitions fromlocalized discoid to various disseminate types of lupus erythematosusmay occur. Conversely, a diagnosis of acute disseminate lupuserythematosus was first established only at postmortem examina-tion of a patient who had cutaneous symptoms for only eightweeks prior to death. The histologic picture of the cutaneouslesions was typical of lupus erythematosus. I cannot agree, there-fore, with a few authors who would separate the localized discoidform from disseminate forms of lupus erythematosus clinicallyor histologically (1, 10, 14, 41).

In many of the eighty cases in which specimens for biopsywere obtained, several specimens were taken at varying intervalsduring the course of the disease. The histologic description isapplicable to lesions occurring anywhere on the body, except asmodified by the absence of granular layer as seen in certain por-tions of the mucous membranes (13) or as modified by a greatdegree of acanthosis and hyperkeratosis when the lesions occuron the palms and the soles. Simply confirming earlier studies(16), it may again be stated that the histologic picture of lupuserythematosus is usually diagnostic if a specimen for biopsy isobtained from a lesion of at least several weeks' duration and froma lesion that has not been subjected to irritating or stimulatingpreparations or to radiotherapy. Rarely is a second specimenfor biopsy necessary to establish diagnosis.

CUTANEOUS CHANGES

The earliest pathologic changes in cases of lupus erythematosusconsist in dilatation of the superficial blood vessels and lymphaticsin the upper part of the cutis. This is followed by extravasationof leukocytes and later of lymphocytes and monocytes togetherwith various changes in the cutis and epidermis. Although theepidermal changes are secondary to the inflammatory changes inthe cutis, they are of diagnostic value. Characteristic pathologicchanges, a combination of which permits a diagnosis of lupuserythematosus to be made, consist of: relative and absolute

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hyperkeratosis; keratotic plugging of the hair follicles and sweatducts; keratotic plugging independent of either; preservation oreven thickening of the granular layer; acanthosis of the prickle-cell layer with adjacent regions of atrophy; liquefaction necrosisof the basal-cell layer; a perivascular, chiefly lymph ocytic, in-filtration about the dermal appendages; dilatation of the super-ficial capillaries and lymphatics; edematous changes in the cutis

FIG. 1. ACUTE Luus ERYTHEMATOSUS OF Six WEEKS' DURATION ON SKIN OFTHE NECK OF A Vt OMAN, AGED FORTY-TWO YEARS

Histologic features in the left side of the section are those of chronic discoidlupus erythematosus, including keratotic plugging of hair follicles and liquefac-tion necrosis of the basal-cell layer. Changes in right side of section are those ofacute disseminate type, including dilatation of superficial vessels and markedatrophy of the epidermis.

and destruction of elastic tissue where the infiltration occurs;a varying number of chromatophores laden with melanin; andabsence of proliferative or obliterative changes in the walls of thedeeper blood vessels.

In the acute and subacute disseminate types of lupus erythe-matosus (fig. 1), dilatation of the superficial capillaries andlymphatics and edema of the cutis, atrophy of the epidermis andliquefaction necrosis of the basal-cell layer become more promi-


nent and the infiltration is usually less marked. The elasticfibers in the beginning are frayed and splintered but later they aredestroyed where the infiltration occurs. As the disease pro-gresses, atrophic changes occur in sebaceous glands and hairfollicles but these may be absent. Sweat glands are likely toshow dilatation but they rarely undergo any marked degree ofatrophic change. The liquefaction of the basal-cell layer appar-ently results from edema and lymph stasis and may be so markedas to result in subepithelial or intra-epidermal formation of bullae.Even in the bullous types of lupus erythematosus, however, thestratum corneum tends to remain intact and usually there is notany evidence of parakeratosis unless there is secondary infectionor ulceration has occurred. In all types of lupus erythematosusthere is a slight but definite increase in the number of Gitter-fäsern (lattice fibers) which suggests involvement of the reticulo-endothelial system (fig. 2). In the stage of involution the infil-tration disappears, the elastic tissue fibers usually are absent,there is a fibrosis of the connective tissues and a flattening andthinning of the epidermis with loss of rete ridges. There mayor may not be residual pigmentation of the basal cells of theepidermis, including the presence of a few chromatophores ladenwith melanin pigment in the cutis.

Satenstein and Diasio would emphasize the presence of baso-philic degeneration and the disappearance of elastic fibers asevidence of a histologic diagnosis of localized lupus erythematosusdiscoides. Further histopathologic studies simply confirmed myprevious report with Goeckerman (16) that basophilic degenera-tion of elastic fibers or merging of elastic and connective tissueto form "collacin" is not diagnostic of lupus erythematosus(12).2 It occurs, it is true, in the majority of sections of lupus

2 Ejiri, in an exhaustive series of studies on elastic tissue made at postmortemexamination of the skin from different parts of the body of individuals of differentages, said that there is no transitional state between the elastic and collagentissue but that the basophilic degeneration is essentially limited to the elasticfibers. This work should be confirmed and I am in agreement with most of theviews expressed. I agree that most of the changes are in the elastic rather thanin the connective tissue fibers but in specimens obtained from a living person withthe use of special stains it would still seem to me that the transition betweenelastic and collagen fibers can be seen microscopically.

PATHOLOGY OF LTIPTJS EHYTHEMATOSTJS 347

erythematosus taken from the exposed surfaces of the body butis almost always absent in sections taken from the covered por-tions of the body—whether one is dealing with a generalizeddiscoid type of lupus erythematosus (chronic disseminate type)or with the subacute or acute disseminate form. Basophilic

FIG. 2. CHRGNIC DISCGID Lurus ERYTHEMATGStJS GN CHEEK GF A MAN, AGEDTHIRTY-FIVE YEARS

Typical histGlGgie changes are evident. Specimen stained with Mareseh-BielsehGwsky stain tG shGw increase GI Gitterfasern (lattice fibers), which arestained black (X 84).

changes in elastic fibers are of constant occurrence in so-calledsenile atrophy of the skin, namely sailors' or farmers' skin; thehistologic changes often are evident at almost any age from earlychildhood. Basophilic changes in elastic and collagen fibers arefrequently seen in other dermatoses including xeroderma pig-mentosum, senile keratosis and roentgen and radium dermatitis.


Edema and swelling of the endothelial cells in the superficialcapillaries and lymphatics may frequently be encountered but,contrary to articles in the literature (1, 22), true proliferative andobliterative changes were seen in this series only in those casesin which patients had been subjected to intensive local radio-therapy. To these may be added the cases reported in theliterature, in which the lupus erythematosus was associated withthrombocytopenic purpura (21, 31) and periarteritis nodosa(18, 30, 50) in which one would of course anticipate some oblitera-tive changes in the vessels in the skin. More will be said laterregarding the vascular changes in lupus erythematosus, under theconsideration of general pathologic changes.

A varying degree of emphasis has been placed on the type ofinfiltrate (49). In the acute disseminate forms in the early stagesvery little infiltrate is seen and this consists chiefly of polymor-phonuclear leukocytes. As the disease progresses it assumesmore the features of the chronic discoid type, the infiltrate be-comes predominantly lymphocytic together with a varyingnumber of plasma cells and monocytes or histiocytes of differenttypes. In the tissue eosinophilia may or may not be present.

Foreign-body giant-cell reaction is not infrequently seen inassociation with destructive changes in the walls of the hairfollicles or as the result of the invagination of the hair and burstingof the wall of the follicle by the hair. Definite tubercle forma-tion was seen in only two cases in this series, in both of which asarcoid and discoid lupus erythematosus were present at the sametime and the multiple diagnoses were confirmed by the subsequentdifferent types of response to treatment of the two conditions.Even those authors who would advocate a tuberculous cause forlupus erythematosus agree that the cutaneous histologic changesin no way suggest cutaneous tuberculosis (9, 26, 38).

Keratotic plugging and atrophy of the epidermis may berecognized histologically long before one can be sure of thesefeatures on clinical examination. Classification as to type oflupus erythematosus or any conclusions in regard to prognosisof a given case, however, cannot be made on the basis of biopsy ofa single lesion or group of lesions. Thus one may happen to

PATHOLOGY OF LTJPIIJS ERYTHEMATOSIJS 349

remove a specimen of a relatively active lesion which is showingfeatures of disseminate lupus erythematosus in a case in which themajority of the lesions and the course of the disease is that ofchronic localized discoid lupus erythematosus. Transitions fromthe histologic picture of acute to chronic discoid lupus erythe-matosus may even be seen in the same section as early as sixweeks after the beginning of the disease (fig. 1). In figure 3

Fio. 3. SUBACTJTE DISSEMINATE Lurus ERYTHEMATOSUS ON CHEEK OF A WOMAN,AGED THIRTY-NINE YEARS

Disease of three years' duration. Clinically the disease was of the chronicdiscoid type. There was a history of previous subacute dissemination. Diseaselater became acute disseminate and the patient died. Histologic changes typicalof subacute disseminate erythematosus with relative and absolute hyperkeratosisand keratotic plugging, atrophy of prickle-cell layer and liquefaction necrosis ofthe basal-cell layer. Slight basophilic changes occurred in collagen fibers.Dilatation of superficial capillaries and lymphatics and perivascular infiltrateincluding dermal appendages.

the histologic picture is that of a subacute disseminate lupuserythematosus yet at the time of examination the clinical picturewas that of chronic discoid lupus erythematosus, whereas therehad been previous dissemination and subsequently an acute dis-seminate lupus erythematosus developed and the patient died ofthe disease. The histologic picture in figure 4 is typical of thechronic localized discoid type, yet three months later dissemina-tion occurred with subsequent fatal termination.


DIFFERENTIAL DIAGNOSIS

There are several conditions which may simulate either theclinical or histologic picture of lupus erythematosus or both.This is especially true of solitary or multiple superficial plaques ofsenile keratosis occurring in an elderly individual and which asyet have shown no malignant change. Most of the histologicfeatures described for lupus erythematosus, usually includingliquefaction necrosis of the basal-cell layer, may also be presentin senile keratosis or leukoplakia of the mouth and genitalia.Atrophic changes in the epidermis, however, are usually minimaland the infiltrate is less marked and is usually limited to the upperpart of the cutis rather than also involving the dermal append-ages. Chronic disseminate and subacute types of disseminatelupus erythematosus may simulate the clinical and histologicpicture of lichen planus, and again careful histologic study may benecessary. The limitation of the infiltrate to the superficialhorizontal network of blood vessels and the relative absence ofatrophic changes or of changes in elastic tissue usually permitdifferentiation. Pityriasis rubra pilaris can usually be distin-guished clinically. Histologically, regions of parakeratosis inrelation to the tips of the papillary bodies and the slight amountof infiltrate suffice for differentiation, even though keratoticplugs and liquefaction of the basal-cell layer are present. Actino-dermatitis is distinguished by obliterative changes in the vesselsin the cutis. The histologic picture of poikiloderma vasculareatrophicans of Jacobi may simulate the telangiectatic or atrophicchanges seen in lupus erythematosus. In fact, at The MayoClinic we have seen several cases in which disseminate types oflupus erythematosus have terminated as a poikiloderma. Inother cases in which a diagnosis of poikiloderma of Jacobi wasmade the disease has terminated as dermatomyositis or lympho-blastoma. Considerable question has been raised lately as towhether poikiloderma vasculare atrophicans is a disease entity.

Disseminate forms of lupus erythematosus may simulate lupuspernio and sarcoid but can readily be differentiated by differenthistologic pictures, except in rare cases in which the two latter

PATHOLOGY OF LTJPTJS ERYTHEMATOSUS 351

conditions are associated. The same is true of psoriasis (15).In cases in which pellagra and eczema are caused by sensitivityto light, examination again may reveal hyperkeratosis; however,parakeratosis and spongiosis are present, but liquefaction necrosisof the basal-cell layer is not present. Erythema multiforme,whether of the idiopathic type or the result of ingestion of drugs,usually reveals changes in the epidermis, frequently a tendencytoward eosinophilic staining, and lack of differentiation of theepidermal cells. As a rule no liquefaction necrosis is present noris keratotic plugging a prominent feature. Lupus erythematosusis readily distinguished from scleroderma and acroscierosis asso-ciated with Raynaud's disease by the absence of obliterativechanges in the vessels and by the varying concomitant findings.Clinically dermatomyositis (23, 51) may simulate acute dissemi-nate lupus erythematosus; histologically, it may simulate acutedisseminate lupus erythematosus to the extent of keratotic plug-ging and perivascular infiltrate involving the dermal appendages.Liquefaction necrosis of the basal-cell layer is usually absent indermatomyositis, and parakeratosis is frequently present. Thehistologic picture is that of a toxic erythema or erythema multi-forme without presenting the cardinal specific features that Ibelieve are necessary for a diagnosis of lupus erythematosus.What has been said about erythema multiforme applies to theso-called Osler erythema group (37) which, according to Keil(21), includes Henoch-Schönlein purpura.

The incidence of epitheliomatous change in lupus erythema-tosus is less than in lupus vulgaris, in which the incidence variesfrom 0.5 to 4 per cent (47, 48, 49). Lupus erythematosus mustnot be regarded as a precancerous condition (32) and most fre-quently the epitheliomas have developed only as a sequel toradiotherapy. When epitheliomas occur they are usuallysquamous cell in type.

The so-called Senear-Usher (43, 54) syndrome has been re-garded as a bullous type of lupus erythematosus or as a relativelybenign form of pemphigus (pemphigus erythematoides—Ormsby(4, 36)). In several cases included in this syndrome the con-dition was simply a bullous form of disseminate lupus erythe-


matosus (46). In some cases the histologic picture in the sub-sequent clinical course has been that of pemphigus (54). In themajority of cases of this syndrome, many of the features of dis-seminate lupus erythematosus have been lacking. Histologically,hyperkeratosis and keratotic plugging have been present butparakeratosis and spongiosis, and intra-epidermal bullae forma-tion without any liquefaction necrosis of the basal-cell layer and

Fin. 4. CHRONIC Discoin Luus ERYTHEMATOSUS ON THE CHEEK OF A MAN,AGED NINETEEN YEARS

Disease of three years' duration. Typical picture with keratotic plugging ofsweat ducts and hair follicles and independent of same; relative and absolutehyperkeratosis, acanthosis and atrophy of epidermis, liquefaction necrosis ofbasal-cell layer and atrophy of dermal appendages. Three months later therewas a typical clinical picture of acute disseminate lupus erythematosus and thepatient died subsequently.

usually with a minimal amount of infiltrate in the cutis also haveoccurred.

The so-called Libman-Sacks syndrome (27), which was firstdescribed as a valvular and mural endocarditis, has come toinclude the presence of fever, leukopenia, petechiae, purpura,embolic phenomenon, evidence of endocarditis, pericarditis, renalinjury, arthritis, pleural effusion and persistently negative bloodcultures (6, 17, 20). The phenomenon has been regarded

If

t

PATHOLOGY OF LUPUS ERYTHEMATOSUS 353

respectively as a separate entity, as related to the Osler erythemagroup, and as acute disseminate lupus erythematosus. Inmany cases the patients have had all the cutaneous and systemicmanifestations of acute disseminate lupus erythematosus. Inother cases the cutaneous symptoms have been absent or haveappeared as transitory erythema and purpura and the clinicaland histologic features of lupus erythematosus have been lacking.A nonbacterial endocarditis, petechiae, purpura, and embolicphenomena are not predominant symptoms of disseminate lupuserythematosus nor is their presence necessary for diagnosis.

GENERAL PATHOLOGIC FINDINGS

The multiple and varied pathologic changes in different organsof the body in cases of disseminate lupus erythematosus havebeen described in a recent paper (33). In the past and at varioustimes, different authors have emphasized the combined involve-ment of various organs, or certain changes in certain organs, asbeing specific for lupus erythematosus (1, 9). Subsequent casesof the Libman-Sacks syndrome have been reported by Baehr,Kiemperer and Schifrin, under the title of "A diffuse disease ofthe peripheral circulation usually associated with lupus erythe-matosus and endocarditis." In many cases described in theliterature (29, 34, 45, 53), however, this syndrome was notpresent and no definite example was present in the series of 154cases of disseminate lupus erythematosus which were seen at theclinic and which I recently reviewed, including fifteen cases inwhich studies were made at necropsy. In seven of these casesa diagnosis of bacterial endocarditis was made. In all the casesin which the hearts were studied at necropsy definite Aschoffbodies were present in the myocardium. The bacteria weredemonstrated by staining sections of the valvular lesions or byblood culture. Baehr and his associates stressed the absence ofAschoff bodies in the myocardium in twenty-two of the twenty-three cases of lupus erythematosus that they studied. Keil (22),Belote (5), Baehr, Kiemperer and Schifrin, and others (10)would all emphasize the vascular changes to be seen in lupuserythematosus. Stickney and also I (33), in a review of the


postmortem findings in fifteen cases, did not find obliterativechanges in the smaller vessels either in the internal organs or inthe skin. It is true in several cases there were terminal infarctsin the liver and spleen but these we believed to be without patho-logic significance. There was also one case in which there wasthrombosis of the peripheral veins and one case in which therewas evidence of Raynaud's disease. Wire-loop type of lesions,described by Baehr and Klemperer as occurring in the kidney inthirteen of twenty cases, were present in only one of our cases.Changes that have recently been described in regard to the kidneyare similar to those occurring in the kidneys in cases of eclampsia(25) and occasionally in infectious disease of long standing. Thesame is true in regard to the rather frequent occurrence of toxicchanges in the liver and spleen, including varying degrees of necrosis,leukocytic infiltration and fatty degeneration about the central veins,and splenitis and splenomegaly. There seems to be nothing specificregarding the pathologic changes seen in association with othersystemic manifestations that are associated with disseminate lupuserythematosus. The most frequent of these changes are arthralgiaand arthritis, anemia, leukopenia and even thrombocytopeniaand blood dyscrasia (33, 40), evidence of renal irritation, at timesnephrosis and nephritis (24, 44), ocular changes, bacterial andnonbacterial endocarditis, toxic hepatitis (45) and splenitis, ef-fusion in serous and synovial membranes, local and general ade-nopathy, gastro-intestinal symptoms (29) and last but not least, aseptic type of temperature. A moderate increase in Gitter-fäsern (lattice fibers) in the liver and kidney and other organs wasseen in several of the cases in this series in which postmortemstudies were made.

The results of bacterial studies have been consistently negativein regard to cutaneous lesions of lupus erythematosus althoughthe Mycobacterium tuberculosis has been demonstrated in acouple of cases following animal inoculation with material ob-tained from a plaque of lupus erythematosus (7). The importanceof the etiologic role played by Mycobacterium tuberculosis variesin different countries, and is probably dependent on the preva-lence of tuberculosis in general in those communities (11, 26,

PATHOLOGY OF LUPUS ERYTHEMATOSTJS 355

29, 34). Keil justly said that the factor of tuberculosis has beenoveremphasized. The most recent articles (5, 19, 29, 34, 40, 42)show very little incidence of active tuberculosis in groups of casesof disseminate lupus erythematosus. Keil also emphasized thatlymphadenopathy should not be diagnosed as tuberculosis whencaseation is the oniy pathologic change to be found (23).

Many cases have been reported in which positive blood cultureswere obtained for streptococci (2, 3, 42, 52) either with or withoutverrucous bacterial endocarditis or pericarditis. Again, pyogenicorganisms cannot be demonstrated in the kidney, liver, spleenor skin and for the time being one may regard changes in allthese organs as simply a manifestation of a general toxemia.

Disseminate lupus erythematosus usually terminates as bron-chopneumonia or lobar pneumonia, with or without pleuritis,pericarditis or peritonitis. Space does not permit a considerationof etiologic factors such as foci of infection and reaction to light,and endocrine disturbances (28, 33, 35, 39, 40).

SUMMARY AND CONCLUSIONS

The cutaneous histologic picture of lupus erythematosus isdiagnostic providing a suitable specimen for biopsy is taken froma lesion which has been present at least several weeks and whichhas not been subjected to previous therapy. All transitionsbetween chronic localized discoid and acute disseminate lupuserythematosus are seen histologically as well as clinically. Thetwo types cannot be regarded as separate diseases. Histologicstudies of the skin often permit a definite diagnosis of lupus ery-thematosus to be established, especially in cases in which thedisease is of the acute disseminate type. A combination of cer-tain pathologic changes is characteristic of lupus erythematosusand permits a diagnosis to be made. Degeneration of elastictissue is not essential for diagnosis; it occurs in many other con-ditions. The differential diagnosis of lupus erythematosus andvarious dermatoses which simulate it usually can be made byhistologic examination.

The Senear-Tlsher syndrome should be separated from lupuserythematosus disseminatus. The so-called Libman-Sacks syn-

356 THE IOURNAL OF INVESTIGATIVE DERMATOLOGY

drome in many cases fulfills the clinical and histologic require-ments of lupus erythematosus but a nonbacterial verrucous en-docarditis, petechiae, embolic phenomenon and renal irritationare not predominant symptoms of disseminate lupus erythema-tosus nor is their presence necessary for such a diagnosis.

One or multiple organs of the body may be involved in casesof disseminate lupus erythematosus. The pathologic changesto be seen in the blood, kidney, heart, liver and spleen are, how-ever, in no case specific for the disease but rather suggest a generaltoxic process.

The reticulo-endothelial system of the entire body, includingthe skin, may be involved without evidence that lupus erythema-tosus is a primary disease of this system. The capillaries in theskin and in various internal organs are involved, but, contrary tothe findings of Baehr, Kiemperer, Schifrin and others (9, 22),proliferative or obliterative changes in the smaller blood vesselsin the skin or in various internal organs do not occur except in anoccasional case of lupus erythematosus disseminatus in whichthere is an associated thrombocytopenic purpura, periarteritisnodosa or Raynaud's disease. The cause of lupus erythematosusremains to be determined. In many cases a streptococcic infec-tion plays a major role (2, 3, 33, 52). Infrequently, activation ofa latent tuberculous focus may result in dissemination anddeath (11).

In the present state of knowledge the diagnosis of lupus erythe-matosus is dependent on recognition of the cutaneous lesions.When in doubt, histologic studies of the skin will often permit thecorrect diagnosis to be made.

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(2) BARBER, H. W.: A case of acute lupus erythematosus. Brit. J. Dermat.,27: 365—371, 1915.

(3) BARBER, H. W.: A case of lupus erythematosus associated with streptococ-cus infection of the tonsils. Brit. J. Dermat., 31: 186—193, 1919.

(4) BECKER, S. W., AND OBERMAYER, M. E.: Pemphigus erythematodes.Arch. Dermat. & Syph., 39: 1918—1919 (May) 1939.


(5) BELOTE, G. H.: Lupus erythematosus disseminatus. Arch. Dermat. &Syph., 39: 793—806 (May) 1939.

(6) BELOTE, G. H., AND RATNER, H. S. V.: The so-called Libman-Sacks syn-drome; its relation to dermatology. Arch. Dermat. & Syph., 33:642—664 (Apr.) 1925.

(7) CANNON, A. B., AND ORNSTEIN, G. G.: The tubercie bacillus as an etiologicfactor in lupus erythematosus. Arch. Dermat. & Syph., 12: 691—699(Nov.) 1925.

(8) CIVATTE, A.: Les recherches sur l'étiologie du lupus érythémateux depuis20 ans. Ann. de dermat. et syph., 7:465—485, 1926.

(9) DENZER, B. S., AND BLUMENTHAL, SIDNEY: Acute lupus erythematosus dis-seminatus. Am. J. Dis. Child., 53: 525—540, 1937.

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(11) DzIoBEic, L., AND CSEH, E.: Zur Frage der Symptomatologie und Atiologiedes Erythematodes acutus. Dermatologica, 79: 201—214 (Apr.) 1939.

(12) Ejini, IsABuno: Studien uber die Histologie der menschlichen Haut. I.Mitteilung: Uber den regionären Unterschied der elastischen Fasernder Haut. Jap. J. Dermat. & Urol., 40: 173—174, 1936.

II. Mitteilung: tiber die Alters- und Geschlechtsverschiedenheiten derelastischen Fasern der Haut. Jap. J. Dermat. & Urol., 40: 216—217,1936.

III. Mitteilung: Uber die regionären- und Altersunterschiede der ver-schiedenen Hautelemente mit besonderer Berucksichtigung derAltersveranderung der elastischen Fasern. Jap. J. Dermat. & Urol.,41: 8—12, 1937.

IV. Mitteilung: tiber das Wesen der Altersverirnderung der Haut. Jap.J. Dermat. & Urol., 41: 64—70, 1937.

V. Mitteilung: Uber die Histologie der menschlichen Haut bei ver-schiedenen Hautkrankheiten, mit Berucksichtigung der Altersveränd-erung der elastischen Fasern. Jap. J. Dermat. & [Jrol., 41: 95—96, 1937.

(13) FINNERUD, C. W.: Em Beitrag zum Lupus erythematodes der Mundschleim-haut. Arch. 1. Dermat. u. Syph., 148: 318—322, 1924—1925.

(14) FRESHWATER, DOUGLAS: The aetiology of lupus erythematosus. Brit. J.Dermat., 24: 57—70, 1912.

(15) GOECRERMAN, W. H.: Psoriasis associated with lupus erythematosus. M.Clin. North America, 15: 1491—1496 (May) 1932.

(16) GOECKERMAN, W. H., AND MONTGOMERY, HAMILTON: Lupus erythematosus;an evaluation of histopathologic examinations. Arch. Dermat. &Syph., 25: 304—316 (Feb.) 1932.

(17) Gnoss, Louis: The heart in atypical verrucous endocarditis (Libman-Sacks). In: Contributions to the medical sciences in honor of Dr.Emanuel Libman by his pupils, friends and colleagues. New York,The International Press, 1932, vol. 2, pp. 527—550.

(18) JARCHO, SAUL: Lupus erythematosus associated with visceral vascularlesions; a series of autopsied cases. Bull. Johns Hopkins Hosp., 59:262—273 (Oct.) 1936.

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(19) KEIL, HARRY: Relationship between lupus erythematosus and tuberculosis;a critical review based on observations at necropsy. Arch. Dermat. &Syph., 28: 765—779 (Dec.) 1933.

(20) KEIL, HARRY: The so-called Libman-Sacks syndrome. Arch. Dermat. &Syph., 34: 124—126 (July) 1936.

(21) KEIL, HARRY: Relation between "systemic" lupus erythematosus and apeculiar form of thrombocytopenic purpura. Brit. J. Dermat., 49:221—237 (May) 1937.

(22) KEIL, HARRY: Conception of lupus erythematosus and its morphologicvariants with particular reference to "systemic" lupus erythematosus.Arch. Dermat. & Syph., 36: 729—757 (Oct.) 1937.

(23) KEIL, HARRY: Tuberculous skin lesions. New England J. Med., 218: 783—784 (May) 1938.

(24) KEITH, N. M., AND ROWNTREE, L. G.: A study of the renal complications ofdisseminated lupus erythematosus; report of four cases. Tr. A. Am.Physicians, 37: 487—502, 1922.

(25) KELLAR, R. J., ARNOTT, W. M., AND MATTHEW, G. D.: Observations on themorbid histology of the kidney in eclampsia and other toxemias ofpregnancy. J. Obst. & Gynaec. Brit. Emp., 44: 320—327 (Apr.) 1937.

(26) KRBN, OTTO: Zur Klarung der Pathogenese des Lupus erythematodesacutus. Wien. med. Wchnschr., 86: 680—683 (June 20) 1936.

(27) LIBMAN, EMANUEL, AND SACKS, BENJAMIN: A hitherto undescribed form ofvalvular and mural endocarditis. Arch. Tnt. Med., 33: 701—737 (June)1924.

(28) LOMUOLT, SVRND: Antileprolbehandlung bei Lupus erythematodes. Der-mat. Wchnschr., 101: 817—829, 1935.

(29) MADDEN, J. F.: Acute disseminate lupus erythematosus. Arch. Dermat. &Syph., 25: 854—875 (May) 1932.

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Documents

Pathology of Lupus Erythematosus - COnnecting REpositories · PATHOLOGY OF LUPUS ERYTHEMATOSUS HAMILTON MONTGOMERY, M.D.' (Received for publication July 17, 1939) Diagnosis of lupus