sarcoidosis-the beginning: historical highlights of personalities and ...

SARCOIDOSIS-THE BEGINNING:HISTORICAL HIGHLIGHTS OFPERSONALITIES AND THEIRACCOMPLISHMENTS DURING THEEARLY YEARSRoscoe C. Young, Jr, MD, Raylinda E. Rachal, MD, and Claude L. Cowan, Jr, MDWashington, DC

Sarcoidosis, an affliction of mankind namedonly as recently as this century, was firstdescribed by Hutchinson in 1878, and noted in asecond patient, one Mrs. Mortimer, in 1898. In1889, Besnier described lupus pernio.

Boeck obtained skin biopsies in 1899.Kreibich described punched-out bone lesionsin 1904. Darier and Roussy described subcuta-neous nodules in 1906, and Heerfordt de-scribed uveoparotid fever in 1909. Schaumannsynthesized the many diverse syndromes ofsarcoidosis into a single disease in a prize-winning essay in 1914. Kveim biopsied thesarcoid skin test-site and established a diag-nostic test in 1941.

Lofgren described the bilateral hilar lymph-adenopathy-erythema nodosum syndrome in1946. In 1954, Israel and Sones helped estab-lish sarcoidosis as an immunologic disorder.In 1963 Cummings compiled a bibliography onsarcoidosis, and in 1966 Siltzbach conductedhis renowned international Kveim test trial.

At Howard University, Harden ignited an

From Howard University College of Medicine, Washington,DC. Presented at the Second University of North CarolinaSarcoidosis Conference, Grove Park Inn, Asheville, NorthCarolina, October 7-9, 1983. A poster session based on thispaper was presented at the 89th Annual Convention andScientific Assembly of the National Medical Association,Montreal, July 29-August 2, 1984, and at the Tenth Inter-national Conference on Sarcoidosis and OtherGranulomatous Disorders, Baltimore, Maryland, September1984. Requests for reprints should be addressed to Dr.Roscoe C. Young, Jr, Division of Pulmonary Diseases,Howard University Hospital, 2041 Georgia Avenue, NW,Washington, DC 20060.

interest in sarcoidosis. In 1944 Johnson andJason contributed to a description of cardiacinvolvement, while Cowan studied ocular in-volvement in sarcoidosis.

Sarcoidosis is a systemic immunologic diseaseof uncertain etiology and prognosis. It is diagnosedby a characteristic clinical picture with compatiblehistopathology of epithelioid cell granulomas inmultiple organ systems of the body, following ex-clusion of known etiologic agents.

Sir Jonathan HutchinsonSarcoidosis has been recognized as an affliction

of mankind for only slightly more than a century.The earliest descriptive accounts of sarcoidosiswere by Sir Jonathan Hutchinson. James G. Scad-ding' 2 referred to Hutchinson as "a remarkableclinical polymath," because he was a surgeon andpresident of the Royal College of Surgeons, as wellas an expert on syphilis and an ophthalmologist.Hutchinson's teeth and Hutchinson's triad bearhis name.

According to Geraint James,3 in 1878, just fouryears prior to Robert Koch's discovery of thetubercle bacillus as the etiologic agent of tuber-culosis, Hutchinson described his first patient withsarcoidosis4:

John W., a policeman, aged 58 years, had a number ofpeculiar dark patches of dark purplish color on the ex-

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SARCOIDOSIS: HISTORICAL HIGHLIGHTS

tremities . . . he had an attack of gout in the metacarpo-phalangeal joint of his left forefinger . . . he finally diedof contracted kidneys

following treatment in King's College Hospital inLondon. James:' concludes "it is tempting tospeculate that Hutchinson's patient's skin lesionsand terminal renal disease were interrelated."

Mrs. MortimerAnother noteworthy patient of Hutchinson was

a Mrs. Mortimer, "a respectable middle-agedwoman" with skin lesions. Hutchinson describedthe case in 1898 in Archives of Surgery.5 He calledthe affliction "Mortimer's Malady" and presentedhis patient to the Dermatological Society of Lon-don. They favored a diagnosis of sarcoma and rec-ommended a biopsy as proof. When Hutchinsontransmitted the conference recommendation to thepatient, she became lost to follow-up for twoyears, and histology was unavailable.

Ernest BesnierIn 1889, Ernest Besnier, a French dermatologist

at l'Hopital Saint-Louis, presented at a meetingin Paris and published the first case of "lupuspernio."6 He described a case of a 34-year-oldman who presented with lesions on the faceand upper limbs "of a type incompletely knownand described." The nose was very large, lividpurplish-red in color and with a shining surface;there were skin lesions on the cheeks. In thehands, synovitis of tendon sheaths was presentwith purplish-red swellings of the fingers. Theswellings in the fingers resembled lupus vulgaris, athen-common form of skin tuberculosis. Becauseof the chilblain-like swelling of the nose and thelupus-vulgaris appearance of the fingers, Besniercalled the disease "lupus pernio."

The patient was presented at the meeting alongwith a series of moulages showing the progressionof the condition. Like Hutchinson, Besnier lackedhistologic material. Finally, in 1892, Tenneson7

showed a case of lupus pernio that had beenstudied histologically.

Cesar BoeckCesar Boeck was a dermatologist from Christi-

ania (now Oslo), Norway. His uncle, Carl WilhelmBoeck, had a patient similar to Hutchinson's JohnW. However, unlike John W., the patient did nothave gout.

In 1899, Cesar Boeck described sarcoidosis ofthe skin and lymph nodes, which were biopsiedand studied histologically.8 He noticed "sarcomagiant cells" bearing a resemblance to those seenin malignant sarcomas, but occurring in "multiplebenign sarcoid." The patient's illness regressed,either because of, or in spite of, therapy consistingof iron, quinine, cod-liver oil, and arsenic, pushedto toxic levels. Boeck noted certain similarities be-tween his case and Hutchinson's Mrs. Mortimer,and believed that if the two diseases were notidentical, they belonged to the same group ofdiseases. He came to believe that the histologicpicture better represented tuberculous lupus ofthe skin, and in his later papers, he renamed it"multiple benign lupoid."

According to Scadding,' the term sarcoidosis(flesh-like) is a misrepresentation. The authorssuspect that Boeck intended to use the termsarcomatoid.

Boeck also recognized that the disease involvedmore than the skin. In some patients, it involvedsuperficial glands, or mucous membranes (con-junctivae), and in others it caused bronchitis.Boeck was, therefore, the first to understandthat the respiratory tract could be involved insarcoidosis.9

Boeck's first patient with sarcoidosis died at 80years of age of a hypernephroma with metastasis.Danbolt, in 1947,10 emphasized that evidence ofprevious sarcoidosis had been absent at the timeof this patient's death. Thus, it was demonstratedthat sarcoidosis could heal by resolution of thelesions, leaving no trace of its former existence.

Roentgen discovered x-rays in 1895. Sevenyears later Kienbock"I published a paper of radio-graphic anatomy of bone changes in a patient withlupus pernio, which he failed to recognize as such.

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Sir Jonathan Hutchinson de-scribed the first patient with sar-coidosis. He also described thecondition of his patient as "Mor-timer's malady."

Ernest Besnier, of Paris, de-scribed "lupus perio," a form ofsarcoidosis involving the nose,cheeks, and fingers.

Mrs. Mortimer, Hutchinson's sec-ond patient with sarcoidosis, asillustrated in Archives of Surgery(London) in 1898.

.~~~ ~~~~~__ W.P.

Cesar Boeck, of Christiania, Nor-way, obtained biopsies of theskin, hence the name "Boeck'sSarcoid."

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Because the patient had a past history of lues, heerroneously described the bone lesions as leutic,rather than caused by sarcoidosis.

Karl KreibichCredit for first noting bone involvement in sar-

coidosis goes to Karl Kreibich in 1904. After grad-uation from medical school in Prague, he workedfor a time in Vienna. He then returned to Prague,where he succeeded Professor Pick as head of thedermatology department. Of the 200 scientificpapers Kreibich published, three dealt with lupuspernio. One patient described was tuberculin-negative. Radiographs of the hands were takenon one of the patients in 1903 and reported inKreibich's paper in 1904. They showed lattice-likerarefactions of the terminal phalanges. Accordingto Levinsky''2:

the x-ray pattern disclosed bone changes within almostall phalanges of the fingers. The x-ray was of good qual-ity, well-reproduced, and showed well-defined multipleradiolucencies situated particularly in the distal heads ofthe second phalanges; a pattern which is at present con-sidered classical.

For most of his life Kreibich regarded thesebone changes as non-tuberculous (so-called lym-phogranuloma). Shortly before his death, underimmense peer pressure, he erroneously concededthat they were probably of a tuberculous nature.

Jungling': is also associated with sarcoidosis ofbone. In 1921, he accurately described bonechanges of the hands and feet in sarcoidosis. How-ever, like his colleagues before him, he wronglybelieved they were a form of tuberculosis. Hecalled it "ostitis tuberculosa multiplex cystica."

In 1906, Darier and Roussy'4 described sixwomen with subcutaneous nodules on the trunkand limbs. On biopsy, the nodules in four of thewomen histologically resembled what Boeck haddescribed in the skin. Therefore, they called themsarcoids. Despite their inability to produce com-parable lesions when tissue suspensions were in-jected into guinea pigs, they believed the nodulesto be of tuberculous etiology. They accordinglyerroneously considered them tuberculides or at-tenuated tuberculosis.

Jorgen Schaumann

Jorgen Schaumann, a Swedish dermatologist,was physician and chief of the Finsen Institute atSt. Gorans Hospital, Stockholm. In 1914, at age35, he presented a paper, "On lupus pernio,"submitted to the Zambaco Prize Committee of theFrench Society of Dermatology and Syphilology. '

Schaumann's essay was unknown to most ofthe medical world for 20 years, however, becauseit remained unpublished until 1934. In it, Schau-mann synthesized the many diverse aspects of sar-coidosis into a single disease entity. On combininghis personal observations with a careful review ofthe literature, he suggested that lupus pernio andBoeck's sarcoid were "6genetically identical"-and only occasional manifestations of a diseasethat affects internal organs. He called the patho-logic change "lymphogranuloma benignum" todistinguish it from malignant lymphoma.'

According to his student, Sven Lofgren,Schaumann advanced the hypothesis that pulmo-nary involvement is often the first stage in thenatural history of sarcoidosis: "Consequently, theinfection is contracted via channels of respiration,and the condition could cause death."

In 1909 Heerfordt,16 a Danish ophthalmologist,described "febris uveo parotidea subchronica,"the syndrome of uveo-parotid fever: uveitis (usual-ly an irido-cyclitis), enlargement of the salivaryglands (especially the parotids), and cranial nervepalsies (especially the facial nerve).

Mikulicz in 1937 described salivary and lacrimalgland involvement in sarcoidosis.'7 It was not rec-ognized until as late as 1937 or 1938, however, thatHeerfordt's disease is a form of sarcoidosis. Thisrecognition came about simultaneously and inde-pendently in the Netherlands on the part of Bruins-Slot'8 and in France by Pautrier.

Lucien-Marie PautrierIn Strasbourg in 1938, Lucien-Marie Pautrier

reported unique pulmonary and lymph node formsof sarcoidosis without skin lesions."' In 1945 hereported a natural history of sarcoidosis beginningwith pulmonary involvement with the ultimate ap-pearance of skin lesions.

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Karl Kreibich, in Prague, de-scribed punched-out bone lesions.

Lucien-Marie Pautrier, of Stras-bourg, discovered that Heer-fordt's uveo-parotid fever was aform of sarcoidosis.

Jorgen Schaumann, of Stock-holm, wrote a prize-winning es-say that synthesized the diversesyndromes into a single disease.

This painting of a pine forestby Schaumann hung over SvenLofgrens desk at St. Goran'sHospital, Stockholm.



Although Boeck had earlier described "bron-chitis" in some cases of sarcoidosis, and Schau-mann vividly discussed the pulmonary involve-ment, credit for the description of pulmonarysarcoidosis goes to Kuznitsky and Bittorf ofBreslau.20 In 1915 they reported the case of a27-year-old man with pulmonary changes demon-strated clinically by chest radiographs. The patientwas a negative tuberculin reactor, and acid-fastbacilli were not found in the sputum. Biopsy ofskin lesions and subcutaneous nodules yieldednon-caseating granulomas. Kuznitsky and Bittorfconcluded that internal organs were involved. Un-aware of Schaumann's essay (as yet unpublishedin 1915), they decided independently that sarcoid-osis constituted a hitherto unrecognized disease ofinternal organs, especially the lungs.

Sven LofgrenA student of Schaumann, also of St. Gorans

Hospital, Stockholm, but a pulmonary physician,Sven Lofgren conducted classical studies of ery-thema nodosum (EN), febrile arthropathy, andbilateral hilar lymphadenopathy. This syndrome,which he inappropriately called "bilateral hilarlymphoma," is known today as Lofgren's syn-drome. Identification of this syndrome increasedthe opportunity for instant recognition of the clini-cal picture of sarcoidosis. Empirically, a goodprognosis was ascribed to this subacute, self-limiting form of the disease.

In a 1946 study,21 Lofgren analyzed 185 cases ofEN and found that 15 of these probably resultedfrom sarcoidosis, despite lack of histologicalproof. He presented histological proof in 25 per-cent of 113 patients with Lofgren's syndrome in a1953 study.22 Lofgren's contribution marks a mile-stone in describing yet another sarcoid syndrome.A painting of a pine forest hung in Lofgren's

office at St. Gorans Hospital for many years. Iron-ically, the artist was Schaumann himself.23

Harold L. IsraelHarold L. Israel helped establish the basis of

sarcoidosis as an immunologic disease. Israel

is currently professor of medicine at JeffersonMedical College, Thomas Jefferson University,Philadelphia. Seventy-five of his 168 contributionsto the medical literature have been concerned withsarcoidosis. In addition to his pioneer work onthe immunology of sarcoidosis, which he sharedwith Maurice Sones,24 he has studied the responseof sarcoidosis patients to BCG vaccination,25 theinterrelationship between sarcoidosis and tubercu-losis, and pulmonary aspergilloma in the chronicpulmonary form of sarcoidosis,26 and done pioneerwork on the value of gallium scanning in thisdisease.27

Although Boeck and Kreibich noted an absenceof skin test reactivity to tuberculin in sarcoidosis,the decreased tuberculin sensitivity in sarcoidosispatients compared with that in the general popula-tion was not generally appreciated until the1940s and 1950s in large series of sarcoidosispatients. In 1952 Friou28_29 found that the antigensof mumps, Candida albicans, and trichophytoncaused delayed skin reactions in a high percentageof healthy adults, but fewer and less intense reac-tions in sarcoidosis patients.

In 1954 Israel and Sones confirmed what Friouhad said with additional observations.24 Theyfound that of those who failed to respond to per-tussis antigen, immunization with pertussis vac-cine caused positive skin tests in all controls,but a transient reaction only in less than one halfof sarcoidosis patients, and no reaction in theremainder.

Shortly thereafter, the list of anergic responsesin sarcoidosis was extended to include other sub-stances, but until recently, the mechanism foranergy was unexplained.

Martin M. CummingsIn 1963, at the suggestion made at the Second

International Conference on Sarcoidosis, MartinM. Cummings, currently Director of the NationalLibrary of Medicine, compiled his famous Bibliog-raphy on Sarcoidosis. It contains 3,952 references,appropriately cross-indexed, on articles publishedthrough 1963.30 Cummings' rational extension ofthe Bibliography on Sarcoidosis was the develop-ment of the present Medical Computerized Infor-mation System, MEDLARS.



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Sven Lofgren, of Stockholm, de-scribed the syndrome of bilateralhilar lymphadenopathy, febrilearthropathy, and erythema nodo-

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Louis E. SiltzbachLouis E. Siltzbach of New York City is to be

remembered as a giant in the research performedon the skin test for sarcoidosis, which now bearshis name. Siltzbach received his medical educa-tion at Downstate in Brooklyn. He trained underErdheim in Vienna, Lowenstein, Felix Fleishner,and Max Pinner. He made 139 contributions to theliterature, mostly on sarcoidosis, skillfully com-bining a knowledge of clinical medicine, immunol-ogy, pathology, and physiology. In addition to hiswork with test suspension, Siltzbach describedthree radiologic stages of sarcoidosis, demon-strated the effect of corticosteroids in suppressinggranuloma formyation, and established a rationalschema for therapy.:" 32

According to Siltzbach, the skin test for sar-coidosis had "an inconclusive beginning." In 1935Williams and Nickerson of Boston:3 observedslowly maturing specific granulomatous papuolesat the intracutaneous injection sites of sarcoidosispatients when sarcoidal spleen suspension wasused as a test preparation. Credit for the test,however, is given to A. Kveim,:4 a dermatologistin Oslo, who put the test on a practical basis. In1941 Kveim reported his observations in 12 of 13sarcoidosis patients following injection of sarcoidlymph-node suspension. He performed a biopsyof the site, and noted formation of epithelioid cellgranulomas similar to those in organs of sarcoido-sis patients.

In 1960 Siltzbach, along with his co-worker,Merrill Chase,353'" reported on a new techniquefor purification and standardization of Kveim testsuspensions at the Second International Confer-ence on Sarcoidosis in Washington, DC. In 1966Siltzbach employed test suspension obtained froma single sarcoidal spleen, in his internationalKveim test trial. In this trial, test suspensionwas distributed to investigators in 37 countriesthroughout the world and studied in 3,244 sub-jects. This survey strengthened the view that sar-coidosis is a single disease entity that is the sameworldwide. In honor of Siltzbach's contribution,Geraint James recommended that the sarcoidosistest suspension be called "the Kveim-Siltzbachtest suspension."

Howard University Hospital, Washington, DC,serves a predominantly black community com-posed of Washington natives, as well as those whohave migrated from the southern states. Many of

these have or will develop sarcoidosis, a majorhealth problem at Howard University Hospital.

K. Albert HardenThe pioneer who stimulated interest in the dis-

ease at Howard University was K. Albert Harden,at one time Dean of the Medical School. He washead of Pulmonary Medicine, founded the HardenPulmonary Laboratory, and was president of theDistrict of Columbia Tuberculosis Association. Hedescribed mechanisms in cavitary pulmonary sar-coidosis,17 contributed many papers on variousaspects of lung function in sarcoidosis,18 and par-ticipated in international conferences.

John B. JohnsonJohn B. Johnson held the chair in Medicine at

Howard in addition to having founded the Cardi-ology Division. He was also president of theAmerican Heart Association. Johnson, in 1944, inconjunction with Robert S. Jason,t was among thefirst to describe sarcoidosis of the heart in aclinicopathologic study.3' In fact, their referencedocumented the discussion on the subject in theCecil and Loeb Textbook of Medicine, a popularmedical school text.

Claude L. CowanAny discussion of sarcoidosis at Howard Uni-

versity would be incomplete without mention ofClaude L. Cowan, Sr, who was chairman of theOphthalmology Service, and was a president ofthe National Medical Association. In 1959 he con-firmed the frequency of eye involvement in sar-coidosis, and described lesser-known clinicaldiagnostic features.4"

Although many of the early pioneer sar-

tDr. Jason died earlier this year. An In Memoriam appearson page 934 of this issue.

894 JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION, VOL. 76, NO. 9,1984


Louis E. Siltzbach, of New YorkCity, prepared Kveim skin testsuspension, conducted Kveimtest trials in 24 different coun-tries, and confirmed that sar-coidosis is a single diseaseworldwide.

John B. Johnson was among theearliest to describe myocardialsarcoidosis.

At Howard University, K. AlbertHarden ignited an interest inpulmonary sarcoidosis.

..

Claude L. Cowan, Sr, describedclinical features of ocular in-volvement in sarcoidosis.



coidologists discussed have gone to their final rest,some remain to continue to unravel the mysteriesof this baffling disease, and to serve as catalysts tostimulate bright young investigators to solve thecontinuing "riddle of sarcoidosis."

Literature Cited

1. Scadding JG. Sarcoidosis. London: Eyre and Spot-tiswoode, 1967, pp 13-21.

2. Scadding JG. Sarcoidosis. Part I-What is sarcoid-osis?, audiocassette CT 566. Hamilton, Ont: McMaster Uni-versity, 1973.

3. James DG. The first hundred years of sarcoidosis.In: Levinsky L, Macholda F, eds. Proceedings of the FifthInternational Conference on Sarcoidosis. Prague: CharlesUniversity Press, 1971, pp 43-48.

4. Hutchinson J. Anomalous disease of the skin of thefingers: Papillary psoriasis. In: Illustrations of Clinical Sur-gery. London: J & A Churchill. 1878, pp 42-43.

5. Hutchinson J. Cases of Mortimer's malady (lupus-vulgaris multiplex, non-ulcerans and non-serpiginous).Arch Surg (London) 1898; 9:307-314.

6. Besnier E. Lupus pernio of the face: Fungoid syno-vitis, scrofulo-tuberculosis of the upper extremities. AnnDermatol Syph (Paris) 1889; 10:333-336.

7. Tenneson M. Lupus pernio. Bull Soc Franc Derma-tol Syph 1892; 3:417-419.

8. Boeck C. Multiple benign skin sarcoid. Norsk MagLaegevid 1899; 14:1321-1334.

9. Boeck C. Further observations on multiple benignsarcoidosis of the skin. In: Festschr F Kaposi, 1900, pp153-168.

10. Danbolt N. Re-examination of C. Boeck's first pa-tient with multiple benign sarcoid of the skin. Schweiz MedWochenshr Schr 1947; 77:1149-1150.

11. Keinbock R. Radiographic anatomy and clinical as-pects of syphilitic bone disease of the extremities. S Heil-kunde 1902; 23:130-185.

12. Levinsky L. Karl Kreibich (1869-1932). In: Levinsky L,Macholda F, eds. Proceedings of the Fifth InternationalConference of Sarcoidosis. Prague: Charles UniversityPress, 1971, pp 63-65.

13. Jungling 0. Osteitis tuberculosa multiplex cystica, apeculiar form of bone tuberculosis. Fortschr Roentgen-strahlen 1919-1921; 27:375-383.

14. Darier J, Roussy G. Subcutaneous sarcoidosis: Con-tribution to study of tuberuclides and tuberculosis attenu-ated in the subcutaneous region. Arch Med Exp (Paris)1906; 18:1-50.

15. Schaumann J. On Lupus Pernio. Memoirs Pre-sented in November 1914 to the French Society of Derma-tology and Syphilology for the Zambaco Prize. Paris:Norstedt and Soner, 1934.

16. Heerfordt CF. On febris uveo parotidea subchronicalocalized in the parotid gland and uvea of the eye, frequent-ly complicated by paralysis of the cerebrospinal nerves.Ugeskr Laeger 1909; 71 :417-421.

17. Mikulicz J. On a peculiar symmetrical disease of thelacrimal and salivary glands. Beitr Clin Festschr TheodorBillroth (Stuttgart) 1892, pp 610-630.

18. Bruins-Slot WJ. Besnier-Boeck's disease and uveo-parotid fever (Heerfordt). Nederl Tijdschr v. Neesk 1936;80:2859-2863.

19. Pautrier LM. Syndrome de Heerfordt et maladie deBesnier-Boeck-Schaumann. Bull Soc Med de Hopital deParis 1937, p 1608.

20. Kuznitsky E, Bittorf A. Boeck's sarcoid with in-volvement of the internal organs. Munchen Med Wschr1915; 62:1349-1353.

21. Lofgren S. Erythema nodosum: Studies in etiologyand pathogenesis. Acta Med Scand 1946; 138(suppl):174.

22. Lofgren S. Primary pulmonary sarcoidosis; earlysigns and symptoms. Acta Med Scand 1953; 145:424-431.

23. Lofgren S. Jorgen Schaumann (1879-1953). In:Levinsky L, Macholda F, eds. Proceedings of the Fifth In-ternational Conference on Sarcoidosis. Prague: CharlesUniversity Press, 1971, pp 52-56.

24. Israel HL, Sones M. Altered immunologic reactionsin sarcoidosis. Ann Intern Med 1954; 40:260-268.

25. Israel HL, Sones M. The tuberculin reaction in pa-tients recovered from sarcoidosis. In: Turiaf J, Chabot J,eds. Reports on the Fourth International Conference onSarcoidosis. Paris: Masson et Cie, 1967, pp 295-298.

26. Israel HL, Ostrow A. Sarcoidosis and aspergilloma.In: Levinsky L, Macholda F, eds. Fifth International Confer-ence on Sarcoidosis. Prague: Charles University Press,1971, pp 495-497.

27. Israel HL, Park CH, Mansfield CM. Gallium scanningin sarcoidosis. Ann NY Acad Sci 1976; 278:514-516.

28. Friou GJ. A study of cutaneous reactions to oidio-mycin, trichophyton, and mumps skin test antigens in pa-tients with sarcoidosis. Yale J Biol Med 1952; 24:533-539.

29. Friou GJ. Delayed cutaneous hypersensitivity in sar-coidosis. J Clin Invest 1952; 31:630-635.

30. Mandel W, Thomas JH, Carmen CT, et al. Bibliogra-phy on Sarcoidosis. Public Health Service, US Departmentof Health Education and Welfare. PHS publication No. 1213,Government Printing Office, 1964.

31. Tierstein A, Festschr LE, Siltzbach LE. Pulmonarysarcoidosis. Mt Sinai J Med 1977; 44:696-697.

32. Siltzbach LE. Pulmonary sarcoidosis. Am J Surg1958; 89:556-568.

33. Williams RH, Nickerson DA. Skin reactions in sar-coid. Proc Soc Exp Biol Med 1935; 33:403-405.

34. Kveim A. On a new and specific cutaneous reactionin Boeck's sarcoid: A preliminary report. Nord Med 1941;9:169-172.

35. Chase MW. The preparation and standardization ofKveim testing antigen, Part 2. Am Rev Resp Dis 1960; 84:86-88.

36. Siltzbach LE. Current status of Nickerson-Kveim re-action. Am Rev Resp Dis 1960; 84:89-93.

37. Harden KA, Barthakur A. Cavitary lesions in sar-coidosis. Dis Chest 1959; 35:607-614.

38. Harden KA, Barthakur A, Carr C. Sarcoidosis: Afunctional classification. Med Ann DC 1959; 18:129-134.

39. Johnson JB, Jason RS. Sarcoidosis of the heart. AmHeart J 1944; 27:246-258.

40. Cowan CL Sr. Ocular sarcoidosis. J Natl Med Assoc1959; 51:371-373.


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