JMS Pearce
Hull, England, United Kingdom

 

Fig. 1 Henrik Sjögren

The esteemed novelist PD James remarked in a book review: “History reminds us of what we are in danger of losing. A glance over our shoulders into medical history may stimulate, challenge, even enhance our own methods and our thinking.“ Although the names of many ancestral physicians are known in eponymous descriptions, the detail and setting of their works are often unknown or forgotten. One example is Henrik Sjögren, whose career was far from blissfully uneventful. The syndrome that bears his name typically affects females aged forty to fifty who suffer from three characteristic symptoms: dryness of the mouth and eyes, fatigue, and joint pains. Neurological manifestationsⁱ are evident in about 16 to 25 percent of cases.ⁱⁱ

 

Henrik Samuel Conrad Sjögren (1899-1986)

Sjögren (Fig. 1) was the son of a successful merchant Conrad Johansson and of his wife Emelie (née Sjögren)¹ in Köping near Stockholm. After school he read medicine at the Karolinska Institutet, where he met Maria Hellgren; the couple married in 1928 in Paris.ⁱⁱⁱ Maria’s father Ulrik Hellgren was an ophthalmologist of repute at Karolinska.

Sjögren graduated in medicine in 1927. Three years later at Serafimer Hospital, he chanced on a forty-nine-year-old woman who suffered from arthritis with extreme dryness of the eyes and the mouth that he termed keratoconjunctivitis sicca. Recognizing the unusual combination of symptoms he presented this patient to the local ophthalmological society, and there learned that his colleagues had not encountered such a case. In 1933,^iv aided by his wife Maria, he described nineteen patients with dry eyes, thirteen of whom also suffered from arthritis. This he presented as a doctoral thesis in 1933, but the work was criticized and Sjögren failed to obtain the status of docent needed for a teaching staff position.² He never complained of this harsh critique he received when defending his thesis.^v In 1935 the Sjögrens, probably reluctantly, left Stockholm and moved to Jönköping, a city on the shores of Lake Vättern, where he was lasarettsläkare (assistant) ophthalmologist. He became in 1938 hospital ophthalmologist to the newly formed Eye Clinic in Jönköping— the first in Sweden.

The importance of Sjögren’s description was not recognized until 1943 when the Australian ophthalmologist Bruce Hamilton translated his thesis into English.^vi This attracted much wider attention than the original German version and secured Sjögren’s international reputation. In 1957 Sjögren belatedly achieved well-deserved recognition, becoming associate professor — docent — at the University of Gothenburg and in 1965 the Swedish government honored him with the title of professor. Over several decades he reviewed the syndrome (Fig. 2) adding eighty personal cases, but he was as candid in his uncertainty as to cause and lack of specific treatment as we are today.^{vii ,viii, ix}

Henrik Sjögren was also an accomplished musician, who in spite of his fame is described by many as a very humble person and by some even as shy. In 1951 he was elected honorary member of The Australian Ophthalmological Society, in 1970 member of the American Rheumatism Organization, and in 1976 of Svensk reumatologisk forening. In 1976 he became a Member of the Royal College of Physicians and Surgeons in Glasgow. Some years after a disabling stroke he died on 17 September 1986 in Lund. He is buried beside his wife at Norra Begravningsplatsen in Solna, Stockholm.

 

Historical reports

Fig. 2 Some problems concerning keratoconjunctivitis sicca and the sicca syndrome

In his original studies, Sjögren ingenuously acknowledged and documented several earlier reports of keratoconjunctivitis sicca similar to his own patients^x — summarized here.

In 1882, T. Leber, had described keratitis filamentosa, a disease characterized by a dry inflammation with filamentous formations of the cornea and conjunctiva.^xi

A sixty-year-old woman with xerostomia and dysphagia was brought before the London Neurological Society in 1887 by Mr. [Jonathan] Hutchinson (1828-1913), who thought this was a nervous disorder.^xii

In 1888, the surgeon Jan Mikulicz-Radecki (1850–1905) reported to the Society for Scientific Medicine in Koenigsberg a forty-two-year-old farmer presenting with painless bilateral swelling of the lacrimal and salivary glands. After surgical excision of the lacrimal glands, and submaxillary glands he found a lymphocytic infiltrate and acinar atrophy. Swelling of the lacrimal and salivary glands with keratoconjunctivitis sicca was called Mikulicz’s disease — considered a variant of Sjögren’s syndrome.^xiii It is now considered a more benign lymphoepithelial IgG4-related plasma cell disorder.

In March 1888, the London physician, WB Hadden (1856-1893) presented a similar case^xiv,xv before the Clinical Society of London: a sixty-five-year-old woman who had a dry mouth and was nearly unable to swallow, “her tongue was red, absolutely dry and cracked like a crocodile’s skin…No tears appeared when she tried to cry.” Hadden reported that the patient was improved by the cholinergic alkaloid pilocarpine.

W. Stock (1874-1956), an ophthalmologist in Tübingen, had described keratoconjunctivitis sicca in patients with extreme dryness of the mouth (1924),^xvi and Henri Gougerot (1881-1955) had also described three women with atrophy of the parotid, submandibular, and mucous glands of the mouth and conjunctiva of uncertain etiology in 1925,^xvii sometimes referred to as Gougerot Sjögren syndrome. AW Mulock Houwer (1884-1983) in 1927 reported the combination of keratitis and chronic polyarthritis, and recognized these manifestations as a syndrome.^xviii

Nobody before Sjögren had realized the systemic nature of the condition.

Primary Sjögren’s syndrome^xix is now recognized as a systemic disease affecting predominantly females with keratoconjunctivitis sicca, fatigue, and joint pains. It is considered a disorder of altered immunoregulation in which there is a lymphocyte-mediated destruction of exocrine glands due to B-cell activation. Neurological manifestations^xx may include cerebral vasculitis, a sensory axonal neuropathy, and mononeuritis multiplex. Complications include thyroiditis, primary biliary cirrhosis, nephritis, cholangitis, and an increased risk of non-Hodgkin’s lymphoma. A secondary type is associated with other systemic autoimmune disease, such as rheumatoid arthritis, systemic lupus erythematosus (SLE), scleroderma, or dermatomyositis.

Antibodies to the Ro (SSA) or La (SSB) antigens, or focal lymphocytic sialadenitis on biopsy of labial salivary glands are useful confirmatory investigations. Muscarinic drugs may give symptomatic relief but no specific treatment has been show to affect the disease process.

Sjögren’s convictions that his “sicca syndrome” was closely linked to rheumatoid arthritis and was a systemic disease^xxi have been confirmed by subsequent research, though its primary etiology remains uncertain. In 1986 the First International Symposium on Sjögren’s Syndrome was held in  Copenhagen.

 

Endnotes

1. The family adopted his mother’s name of Sjögren for legal reasons in 1923.
2. “With today’s knowledge, it can be said that much of the criticism was wrong and unfair.” (Magnus Carlsson, Jonkoping, The Moisture Seekers® Newsletter; Sjögren’s Syndrome Foundation Inc. September 2008).

References

1. Fauchais AL, Magy L., Vidal E.  Central and peripheral neurological complications of primary Sjögren’s syndrome. Presse Med. 2012 Sep;41(9 Pt 2):e485-93. doi: 10.1016/j.lpm.2012.06.002. Epub 2012 Jul 26.
2. Lefaucheur J-P, Sène D, Oaklander AL. Primary Sjögren’s Syndrome. N Engl J Med 2018; 379:96-97.
3. Wollheim FA. A humble gentleman at 100. In: Classics in Rheumatology edited by T. Pincus. Clin Exp Rheumatol 1999; 17: 648-652.
4. Sjögren H. Zur Kenntnis der keratoconjunctivitis sicca. Keratitis filiformis bei Hypofunktion der Tränendrüsen [On knowledge of keratoconjunctivitis sicca. Keratitis filiformis due to lacrimal gland hypofunction] Acta Ophthalmol. 1933;2:1–151.
5. Theander E,. Wollheim FA. Recollection of Henrik Sjögren. In: R.I. Fox, C.M. Fox (eds.), Sjögren’s Syndrome, DOI 10.1007/978-1-60327-957-4_2, 11 © Springer Science+Business Media, LLC 2011
6. Sjogren, H. A New Conception of Keratoconjunctivitis Sicca (Keratitis Fili- formis in Hypofunction of the Lacrymal Glands). (Translated by J. Bruce  Hamilton.) Australasian Medical Publishing Company, Ltd. Glebe, N.S.W., Australia, I943, I52 pp..
7. Sjögren, H. Keratoconjunctivitis Sicca. In: Ridley, F., and Sorsby, A. (eds.) Modern Trends in Ophthalmology. Butterworth & Co.,Ltd., London, I940; 403-4I3.
8. Sjögren H. Some problems concerning keratoconjunctivitis sicca and the sicca syndrome. Acta Ophthalmologica Scandinavica 1951; 29: 33-47.
9. Gerli R, Bartolini E, Alunno A. (Eds) Sjögren’s Syndrome: Novel Insights in Pathogenic, Clinical and Therapeutic Aspects. London, Academic Press: Elsevier 2016
10. Sjögren, H. Keratoconjunctivitis sicca, in Transactions of the Ophthalmology Section of the Swedish Medical Association, 1929–1931, In: Acta Ophthalmol. 1932;10:403–409.
11. Olschowka N. The History of Henrick Sjögren. Association du syndrome de Sjögren. sjogrens.ca/en/the-history-of-henrick-sjogren
12. Hutchinson J. A Case of “Dry Mouth”. Trans. Clin. Soc. Lond 1888;21:180- 181.
13. Morgan WS, Castleman B. A Clinicopathologic Study of “Mikiulicz’s Disease.” Am J Pathol. 1953;29(3):471-503.
14. Hadden WB. Xerostomia (Dry Mouth). Brain 1889;11:484-486.
15. Ghafoor M. Sjögren’s Before Sjögren: Did Henrik Sjögren (1899–1986) Really Discover Sjögren’s Disease? Journal of Maxillofacial & Oral Surgery. 2012;11(3):373-374.
16. Stock W. Pathology of the tear organs. Berlin: J. Springer, 1925
17. Gougerot H. Insuffisance progressive et atrophie des glandes salivaires et muqueuses de la bouche, des conjonctives (et parfois des muqueuses nasale, laryngée, vulvaire), sécheresse de la bouche, des conjonctives, etc. Bulletin de la Société française de dermatologie et de syphiligraphie, Paris, 1925, 32: 376.
18. Mulock-Houwer A. W. (1927) Keratitis filamentosa and chronic Arthritis. Trans Ophthal Soc U K 1927;47: 88.
19. Xavier M, Criswell LA.  Primary Sjögren’s Syndrome. N Engl J Med 2018; 378:931-939.
20. Fauchais AL, Magy L., Vidal E.  Central and peripheral neurological complications of primary Sjögren’s syndrome. Presse Med. 2012 Sep;41(9 Pt 2):e485-93. doi: 10.1016/j.lpm.2012.06.002. Epub 2012 Jul 26.
21. Sjögren H Keratoconjunctivitis sicca and chronic polyarthritis. Acta Med Scand. 1948;130(5):484-8.

 

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JMS PEARCE MD, FRCP is an Emeritus Consultant Neurologist at Hull Royal Infirmary.

 

Summer 2018  |  Sections  |  Physicians of Note