Clinical Research on Sarcoidosis in Finland
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Review SARCOIDOSIS VASCULITIS AND DIFFUSE LUNG DISEASES 2018; 35; Suppl 1: 9-79 © Mattioli 1885 Clinical research on sarcoidosis in Finland Early clinical reports und über das Bild dieser Krankheit in Lichts der Reaktionsergebnisse. (About the intracutaneous Kuhlefelt E. Ett fall av febris uveoparotidea Kveim reaction in lymphogranulomatosis benigna subchronica (Heerfordt), (A case of subchronic and the clinical picture in light of the reaction fea- uveoparotid inflammation, Heerfordt), Finska tures). Acta derm-venereol ( Sthlm) 1943;23, suppl Läk-Sällsk Handl 1916; 58:867-870 (in Swedish) 10:1-194 (in German) (3). (1). The manuscript was translated to English and published with the English title in Br J Ophthalmol Putkonen T. Über die Kveimreaktion by Lym- 1917; 1:621-623. Kuhlefelt described a disease in a phogranulomatoisis benigna. Mit einem Beitrag 21-year old woman who suffered from joint pain, zur Thermostabilität und Haltbarkeit des Anti- bilaterally enlarged parotic glands and right-sided gens. (About the Kveim reaction in lymphogran- uveitis. Kuhlefelt mentioned that a similar type dis- ulomatosis benigna. With contribution to the ease had been described by Heerfordt. He regarded termostability and validity of the antigen). Acta the disease as a type of tuberculosis. It was not un- derm-venereol ( Sthlm) 1945; 25:393-410 (in Ger- til 1936-37 the uveoparotid fever was classified as a man) (4). type of sarcoidosis. Putkonen T. Lymfogranulomatosis benigna ja Cedercreutz A. “Krankenvorstellungen” (Case Kveimin reaktio (Lymphogranulomatosis benigna reports) Förhandlingar vid Nordisk Dermatolo- and the Kveim reaction). Duodecim 1945; 61:223- gisk Förenings 10:de möte I Helsingfors, Mercator, 243 (in Finnish) (5). 1939: 701” (2). Cedercreutz was a dermatologist and reported the histories of four cases of Boeck’s sarcoid Putkonen T. A case of skin tuberculosis with a at the Nordic Dermatolgy congress in Helsinki in positive Kveim’s reaction as late as five years after 1938. All four patients had skin lesions on the face injection of antigen. Acta Derm Venereol Suppl and two of them had changes in the hilar regions in (Stockh). 1952;32(29):294-296 (6). chest radiographs. Putkonen T. The Kveim reaction. Acta tuberc scand 1959; 38, suppl 45:24-31 (7). Clinical Research 1943-2017 Putkonen prepared Kveim material from lymph nodes and noticed that material from a patients who The first scientific publications in Finland related to reacted weakly themselves or not at all to Kveim ma- sarcoidosis were written by a dermatologist, Tauno terial was more potent than material from patients Putkonen, and delt with the Kveim test. He pub- who reacted strongly and rapidly to the intradermally lished a series of publications starting with his aca- injected material. Due to the limited amount of test demic thesis: material from each source it was difficult to stand- ardize the test. Despite a lot of research the active Putkonen T. Über die Intrakutanreaktion von principle in Kveim material has remained unknown Kveim (KvR) bei Lymphogranulomatosis benigna and the test is no longer in clinical use. 10 O. Selroos In the 1950’ies not much happened around sarcoido- 1973 Maija Horsmanheimo. Lymphocyte trans- sis in Finland. The internists Kuhlbäck and Nyberg formation in sarcoidosis, Helsinki University (14). reported on hypercalcaemia and renal failure and Aho et al published a paper about spontaneous pneumo- 1975 Pentti Tukiainen. Needle biopsy in diffuse thorax in three patients with pulmonary sarcoidosis: lung manifestations. An analysis of 145 consecu- tive cases, Helsinki University (15). Kuhlbäck B, Nyberg W. Hyperkalcemi och njur- skada vid sarkoidos (Hypercalcaemia and renal 1979 Anni Karma. Ophthalmic changes in sar- failure in sarcoidosis). Finska Läk-Sällsk Handl coidosis, Oulu University (16). 1955; 98:181-185 (in Swedish) (8). 1980 Carola Grönhagen-Riska. Angiotensin con- Aho A, Heinivaara O, Mahonen H. Boeck’s sar- verting enzyme and sarcoidosis, Helsinki Univer- coid as a cause of spontaneous pneumothorax. Ann sity (17). Med Intern Fenn 1958; 47:163-167 (9). 1983 Juhani Elo. Sarkoidoosi. Kliininen tutkimus These papers will be discussed in more detail below. Varsinais-Suomen tuberkuloosipiirissä vuosilta 1965-1977 (Sarcoidosis. A clinical study in the tu- As mentioned before the real start of sarcoidosis re- berculosis district of South-Western Finland in search in Finland goes back to the 1963 international 1965-1977), Turku University (in Finnish) (18). congress on sarcoidosis in Stockholm (10). 1985 Elli Koivunen. Hematologiset löydökset sarkoidoosissa (Haematological findings in sar- Academic dissertations coidosis), Tampere University (in Finnish) (19). A total of 14 academic dissertations dealing with sar- 1986 Virpi Oksanen. Neurosarcoidosis. A clinical, coidosis have been defended at universities in Fin- laboratory and neuroradiological study, Helsinki land: University (20). 1943 Tauno Putkonen. Über die Intrakutanreak- 2000 Anne Pietinalho. Sarcoidosis in Finland and tion von Kveim (KvR) bei Lymphogranulomatosis Hokkaido, Japan. A study of two genetically differ- benigna und über das Bild dieser Krankheit in Li- ent populations, Helsinki University (21). chts der Reaktionsergebnisse. (About the intracu- taneous Kveim reaction in lymphogranulomatosis 2014 Annika Wennerström. The extended MCH benigna and the clinical picture in light of the reac- haplotypes and their role in sarcoidosis, Helsinki tion features) (3). University (22). 1968 Kari Määttä. Histological study of mediasti- 2015 Riina Kandolin. Cardiac sarcoidosis and gi- nal lymph nodes in clinical sarcoidosis. A report of ant cell myocarditis in Finland. Helsinki Univer- 86 cases, Turku University (11). sity (23). 1969 Olof Selroos. The frequency, clinical picture and prognosis of pulmonary sarcoidosis in Fin- Epidemiology land, Helsinki University (12). Riska N, Selroos O. Clinically diagnosed sar- 1971 Matti Hannuksela. Erythema nodosum with coidosis in Finland in 1960. Acta tuberc pneum special reference to sarcoidosis. A clinical study of scand 1964;44:267-275 (24). Riska and Selroos col- 343 Finnish adult patients, Helsinki University lected data on all patients who had been hospitalized (13). because of sarcoidosis in Finland in the year 1960. A total of 71 cases with definite or probable diagnosis One hundred years of sarcoidosis research in Finland (1916-2017) 11 of sarcoidosis were found among a population of 4.8 seen between the areas in the study. No statistically million giving a prevalence of 1.59/105. It is obvious significant correlation was noticed between tubercu- that sarcoidosis at this time was a less well known losis and sarcoidosis. There were more female than diseases in Finland and probably often misdiagnosed male patients (2:1). Most female patients were seen as tuberculosis. in the 40-49 year age group and most males in the 30-39 year age group. Pätiälä J, Riska N, Selroos O. Sarcoidosis in Fin- land. Acta med scand 1964; 176, suppl 425:110 Elo studied sarcoidosis in the Southwestern part of (25). In 1960-1961 a total of 1 450 000 mass chest Finland (18). In this district the mean annual inci- radiographic surveys were performed in Finland. dence of sarcoidosis in 1974-1977 was 17.6/105 in- Based on the radiographs the prevalence of sarcoido- habitants. The prevalence based on mass chest radio- sis was estimated to be 4.6/100 000 pictures. In 60% graphic examinations in 1971-1980 was 102/105. of the cases the diagnosis had been confirmed by tissue biopsies. In the same report the prevalence of Poukkala A, Huhti E, Lilja M, Saloheimo M. In- diagnosed cases in a district of southern Finland – cidence and clinical picture of sarcoidosis in a cir- the tuberculosis district of Raseborg – was 5.1/105 cumscribed geographical area. Br J Dis Chest 1986; inhabitants. 80:138-147 (27). A few years later (1970-1981) the mean annual incidence of sarcoidosis in northern Selroos O. Frequency and nature of sarcoidosis in Finland was 14.2/105. southern Finland. In: La Sarcoïdose, (eds. J Turiaf & J Chabot), Masson et Cie, Paris ,1967 pp 369- Selroos O, Pietinalho A, Löfroos A-B, Hellström 372 (26). In a further mass radiographic survey in P-E, Riska H. Sarcoidosis in Southern Finland the Raseborg district in 1959-1965 the prevalence of 1981-1985. Sarcoidosis 1992; 9, suppl 1: 125-128 sarcoidosis was estimated to a mean of 8.1/105. In the (28). Sarcoidosis was diagnosed in 193 patients, 86 same period the annual incidence of new cases in- women and 61 men; 147 (76%) were biopsy proven. creased gradually from 2.0/105 inhabitants above the Patients without biopsy support were mostly women age of 15 years in 1959 to 16.1/105 in 1965. There with Löfgren’s syndrome where biopsy support is were twice as many women as men. Erythema nodo- normally not necessary. Thirty-one % of the patients sum was 10 times more common in female patients. belonged to the age group 30-39 years where also most males were seen, 43%; most female patients As part of his academic thesis Selroos estimated the were seen in the age group 40-49 years, 29%. frequency of sarcoidosis in entire Finland (12). In the 1960’s Finland was divided into tuberculosis dis- Pietinalho A, Hiraga Y, Hosoda Y, Löfroos A-B, tricts and these were further divided into 46 smaller Yamaguchi M, Selroos O. The frequency of sar- administrative areas – tuberculosis dispensary areas. coidosis in Finland and Hokkaido, Japan. A com- In these 46 areas the actual situation of tuberculosis parative epidemiological study. Sarcoidosis 1995; was determined by calculating the number of new 12:61-67 (29).The most recent epidemiological data tb-positive cases, the number of patients with pul- on sarcoidosis in Finland comes from the work by Pi- monary tuberculosis listed in the registry, the number etinalho et al. In 1984 they reported a prevalence of of chronic cases, and the number of fatal cases. Based 28.2/105 and an annual incidence of 11.4/105.