Acta Medica Scandinavia. Vol. CXL, faec. I, 1951.

From the medical department, Garrison Hospital, Boden, Sweden.

Nephropathia Epidernica a New Infectious Disease in Northern Scandinavia

BY

GUSTAF MYHRMAN*

(Submitted for publication November 6, 1950.)

In the autumn of 1933 and in the spring of 1934 the author observed in Ostersund in the county of Jamtland seven cases of a renal disease that had a peculiar clinical picture. I t was characterized by acute onset without preceding infectious disease, with chills, fever and headache, heavy proteinuria, which dis- appeared in a short time, a scanty urine sediment, hyposthenuria, slightly decreased glomerular filtration, elevation of nonprotein nitrogen but no elevation of the blood pressure. The course of the disease was short and benign. All patients recovered.

Independently Zetterholm in the spring of 1934 described seven ))cases of acute nephritis simulating acute abdominal surgical disease)), which he had observed in Skelleftei in the county of Vasterbotten. I t seems quite clear from his description that it was the same disease. Thus Zetterholm seems to have been the first t o mention the disease.

Cases of the same type were described by Oldberg in 1941 in a material con- sisting of 80 cases of acute nephritis observed in Skelleftea 1933-1940.

During the summer of 1942 Stuhlfauth and Hortling observed among German and Finnish troops in Finnish Lapland an epidemic outbreak of a disease, which had, in most respects, the same character as the disease observed by Zetterholm and by the author.

During the last few years the author has had the opportunity of observing in Boden in the county of Norrbotten about 30 cases of the disease. Many of the author’s colleagues in this waste country have also given him reports of similar cases.

* Orebro. Sweden.

NEPHROPATHIA EPIDEMICA - A NEW INFECTIOUS DISEASE IN NORTHERN ETC. 53

Hallqvist has reported in 1948 one case from Gavle in the county of Gavle- borg. Coster & Lublin report some 10 cases observed during the last two and a half years in Hudiksvall in the county of Gavleborg. *

From Norway, Knutrud in 1949 has reported cases observed in Hamar in the county of Hedmark. Muri in 1950 has described 14 cases from Lillehammer in the county of Opland.

Because no report of the disease has been published in the English literature, the author thought that it might be of interest to give a brief account of this disease.

The author has suggested the name nephropaihia epidemica for the disease. The renal syndrome, which is the most striking feature of the disease, seems reasonable justification for the first name. There may be some doubt as to the attribute epidemica. I t has been criticized by Coster & Lublin. The author’s cases were mostly sporadic ones but small accumulations of cases have been observed from time to time. Muri also found epidemic accumulation of cases and Stuhlfauth and Hortling observed a real epidemic.

Coster & Lublin do not believe that the condition is a clinical entity but rather ))a mode of reaction in certain individuals,. I t remains to be explained why these individuals are to be found only in Northern Scandinavia.

I

Etiology and epidemiology

The etiology of this disease is unknown. Stuhlfauth suspected a Lepiospira infection but no agent was demonstrated. Among those who have studied the disease no one has been able to demonstrate any etiologic agent. The author has, in a considerable number of cases, had the patient’s serum carefully examined for agglutinins to different species of Lepiospira: L. Iciero-hemorrhagiae, Sejroe, canicula, Baiauia, grippoiyphosa and Pomona, always with a negative result. In a number of cases urine or blood has been injected intraperitoneally into guineapigs without occurrence of leptospirosis. Spirochetes could never be found in the urine sediment. The author tried to transfer the disease to himself by ingesting 15 ml of urine and by intramuscular injection of 5 ml of blood. The results were negative.

Stuhlfauth and Hortling observed an epidemic outbreak during the Second World War in Finnish Lapland. Muri in Norway observed the occurrence of the disease in a gang of timber workers. The author in some instances heard of similar cases observed in the patient’s neighbourhood. The transfer of the dis- ease from one person to another has never been observed. The disease has occurred with sporadic cases spread over a very waste territory.

The disease is observed chiefly among people living under poor hygienic condi- tions. The author’s material like that of Muri ciefly consists of lumberers. Stuhl-

54 GUSTAF MYHRMAN

fauth and Hortling observed the disease among soldiers. The author has observed three cases among women. One of them worked as a cook in a gang of lumberers.

The occurrence of the disease gives some reason to assume that i t is propagated from an animal source. The author has found it more and more likely that mice are the vectors of the contagium. The primitive dwellings of the lumberers during their work in the big forests are often infested with mice. In a considerable number of cases the patients have stated that they have observed mice. Muri seems to entertain a similar opinion and he has quoted confirmatory examples. The majority of cases observed by the author have occurred during the winter season.

Symptoms and clinical pathology

The onset of the disease is acute, with fever, chills and intensive malaise. After a short time the patient complains of headache and pains everywhere, specially in the abdomen and in the back. The pains can be so intense that the patient moans and has difficulty in keeping still. There is often tenderness over the ab- domen and over the kidneys. Vomiting is common. The sensation of feeling severely ill makes the patient call for the physician. The abdominal symptoms raise suspicion of appendicitis and several of the author’s cases have been sent by airplane to a surgical ward as ))acute abdomen)).

The fever usually subsides within a few days. This initial phase is followed by a renal syndrome which is the characteristic

feature of this disease. There is a proteinuria, usually of a moderate degree. The author has observed

quantities up to 6O/,. In one of the author’s cases Dr. B. Olhagen has made an electrophoretic analysis of the protein content of the urine. This analysis gave the following result:

Alb. fa-globulin /?-globulin y-globulin

66.7 % 12.8% 20.5 %

Insufficient separation between the albumin gradient and the a-globulin prevented an exact analysis of the distribution of these components (which, according to Olhagen, is a common phenomenon in urine protein analysis). The a-globulin probably does not amount to more than 1: 10 of the albumin and the distribution of the fractions resembles that found in nephrotic proteinuria, whereas the proteinuria in nephritis contains a relatively larger amount of albumin. According to Olhagen the electrophoretic findings indicate that the pathogenesis of the proteinuria in this disease is of the same kind as in nephrosis, that is leakage from the glomeruli,

I t is most characteristic that the proteinuria usually disappears between the 9:th and the 13:th day.

NEPHROPATHIA EPIDEMICA - A NEW INFECTIOUS DISEASE IN NORTHERN ETC. 55

The quantity of urine is low a t the beginning of the disease, but after few days a polyuria sets in, with excreted quantities of 3-4 liters or even more.

The author desires to stress that when the disease is fully developed the specific gravity of the urine is low. This symptom is important in the identification of the disease. Muri, who had the opportunity of observing the patients in an earlier stage of the disease than did the author, has found normal specific gravity during the first few days after the onset. In the author’s cases, examined after 4-5 days’ illness the specific gravity of the urine was always low. After ingestion of 1 liter of water, an almost, complete isosthenuria is observed. This isosthenuria can persist for a long time. The author has observed it in one case after more than two months.

The creatinine clearance is more or less diminished. The urine sediment is scanty: a few red and white corpuscles and casts. The

author has never observed hematuria but two patients have claimed to have observed blood in the urine.

Examination of the patient’s blood reveals an increase of nonprotein nitrogen, which may be moderate in the earlier stage of the disease but can reach a high level later on. The author has found up to 180 mg%. I t is a characteristic,feature that this increase reaches its maximum a t a time when the patient already begins to feel better.

The protein content of the blood plasma has been analysed electrophoretically in two cases by Dr. B. Olhagen. This analysis gave the following result:

Total Alb. a-glob. P-glob. y-glob. Fibrinogen

Case 6 6.5 47.2 11.7 13.9 16.7 10.5 Case 7 7.8 45.9 13.9 13.5 18.7 8.0

The increase of the a-globulin and of the fibrinogen indicates an acute infection. The sedimentation rafe of the red corpuscles usually has been moderately in-

No morphological changes of importance have been observed in the blood. The thymol turbidity test has been performed in 16 cases. In 11 i t was

Elevation of the blood pressure has never been observed. In one case the author observed a slight increase in the size of the liver.

Icterus was never observed. The spleen was never enlarged. Slight edema in the face has been observed in a few cases and in some cases the recovery was followed by a weight loss of a few pounds indicating the existence of latent edema.

During the epidemic in Finland Stuhlfauth observed in nearly 25% of his cases characteristic eye symptoms consisting of disturbance of distant vision. In one case, the author observed a disturbance of this type. I t disappeared rapidly. In a few cases, the patients have mentioned uncharacteristic eye symptoms.

creased, to 30-40 mm a t the acme of the disease.

positive.

56 GUSTAF MYHRMAN

Diagnosis

The clinical picture of the disease is so characteristic that the diagnosis can be established immediately. I t is impressive that the patients feel very sick, and for this reason they often call the doctor. The severe abdominal symptoms can raise suspicions of acute appendicitis. The proteinuria, the low specific gravity of the urine and the increase of the nonprotein nitrogen level, facilitate the diagnosis. The clinical picture is completed by the regular and benign course. The dis- appearance of the proteinuria can be predicted almost to a day. If the patient feels sick a t the onset of the disease it is also characteristic that he feels com- pletely recovered long before the nonprotein nitrogen has reached the normal level and defore the other renal symptoms have disappeared.

The disease is so entirely different from other acute renal diseases such as glomerular nephritis or field nephritis that there can scarcely be any mistake.

Prognosis and treatment

The course has in the author’s cases always been favorable and this is one reason why the author is inclined to doubt the diagnosis in one of Knutrud’s cases, which ended lethally. The disturbance of the kidney function can persist for a long time, but the patients recover completely.

The author has not found it necessary to give any special dietary or medica- mentary treatment. The patients were allowed to eat the ordinary hospital diet. They were usually discharged before the nonprotein nitrogen had returned to normal level.

Summary

The author gives a brief monographic survey of nephropatia epidernica, a benign infectious disease, observed in northern Scandinavia. The most outstanding feature of the disease is a renal syndrome of nephrotic type.

Bibliography ’ Coster, C. & Lublin, H.: Acta medscand. 195O:supp1.234:46. - Hortling, H.: Nordisk Medicin 1946:30:1001. - Hallqvist, B.: Svenska Lakartidningen 1949:46:985. - Knutrud, C.: Tidskrift for den norske lsegeforening 1949 nr 11. - Lublin, H.: Svenska Lakartid- ningen 1949:46:1166. - Muri, J.: Nordisk Medicin 1950:43:290. - Myhrman, G.: Nordisk Medicinsk Tidskrift 1934:7:793; Nordisk Medicin 1945:28:2571; Nordisk Medicin 1948:40: 1770. - Oldberg, S.: Nordisk Medicin 1941:10:1933. - Stuhlfauth, K.: Deutsche med. Wochenschr. 1943:69:439. - Zetterholm, S. G.: Svenska Lakartidningen 1934:31:425.