Older sarcoidosis patients: experience of a medical center in Turkey.

Objectives: Although sarcoidosis is classically defined to be a disease of young adults, it might also be seen at older ages. There are very few clinical studies which focus on the features of patients diagnosed at older ages. In this study, we tried to determine the frequency of patients diagnosed at or above 50 years of age and to compare the clinical and demographic features of these subjects with other sarcoidosis patients.

Methods: We evaluated the general clinical features of sarcoidosis patients more than 50 years of age who were diagnosed at our center within a 36-year period. We also compared the clinical features of older sarcoidosis patients with the features of other patients.

Results: Of 579 sarcoidosis patients being followed up at our center, 102 (17.7%) were older than 50 years of age at the time of initial diagnosis. The female to male ratio in this group was higher than the ratio in other sarcoidosis patients (3.43 versus 1.85, P = 0.015). When the features of older patients were compared with other sarcoidosis patients, extrapulmonary involvement was observed to be more common in this group (P < 0.001). By contrast, arthritis or arthralgia (P < 0.001), clinical presentation in the form of Lofgren syndrome (P < 0.001), erythema nodosum (P < 0.001), and uveitis (P = 0.006) were less frequent.

Conclusions: Although generally presenting as a disease of the young, in many subjects sarcoidosis is diagnosed at older ages, and this study indicates that the clinical features of sarcoidosis in older subjects differ from those found among younger patients.

Key Words: erythema nodosum, Lofgren syndrome, old age, sarcoidosis, uveitis

**********

Sarcoidosis is a disease of unknown etiology that is characterized by the formation of noncaseating granulomas in many systems. Sarcoidosis might be seen at any age, however it generally occurs between 20 and 40 years of age. (1) The percentage of older sarcoidosis patients varies in different series. There are a few studies about the clinical features of subjects diagnosed with sarcoidosis at older ages. (2)

In our study, we evaluated the general clinical features of sarcoidosis patients more than 50 years of age who were diagnosed at our center within a 36 year period. We also compared the clinical features of older sarcoidosis patients with the features of other patients.

Materials and Methods

Five hundred seventy-six sarcoidosis patients being followed up at the Cerrahpasa Medical Faculty, Department of Internal Medicine, Division of Lung Diseases between 1966 and 2002 were included in the study. Demographic and clinical features, radiologic stage at initial diagnosis, presence of extrapulmonary involvement, results of Kveim and tuberculin (Mantoux) tests of 102 sarcoidosis patients who were more than 50 years of age at initial diagnosis were obtained retro-spectively from the hospital records. The features of these patients were compared with the features of 474 patients less than 50 years of age.

Clinical, radiological, and histopathological data were used to diagnose sarcoidosis. The presence of noncaseating granulomas in the histologic examination of at least one tissue specimen, the absence of mycobacteria and fungi in tissues and cultures, and the exclusion of other granulomatous diseases were deemed necessary for diagnosis. In 44 of 102 older sarcoidosis patients, the disease was diagnosed by the histologic examination of tissue obtained by transbronchial biopsy. The other methods of diagnosis are given in Table 1.

The classifications of De Remee (3) were used to describe chest radiographs. Here, stage I meant bilateral hilar lymphadenopathy (BHL); stage II, BHL plus parenchymal infiltration; and stage III, parenchymal infiltration without BHL.

[chi square] test was used for statistical evaluation of the data.

Results

Of 576 sarcoidosis patients (387 females, 189 males), 102 (17.7%) were more than 50 years of age. Seventy-nine of those were females and 23 were males. Radiologically, 8 patients had stage 0 disease, 52 stage I disease, 31 stage II disease, and 11 had stage III disease. Seventy-eight (76.5%) patients had extrapulmonary involvement. The involved sites were as follows: skin (26 patients), peripheral lymph nodes (19 patients), liver and erythema nodosum (8 patients each), parotid gland (5 patients), spleen (4 patients), bone cysts (3 patients), lacrimal gland, uvea, orbita, optic nerve, arthritis (2 patients each), muscle and bone marrow (1 patient each).

Kveim test results were available in 50 patients, and were positive in 35 (70%). Mantoux test was performed in all cases and it was positive in 31 (30.4%) patients. The results of these two tests in the older sarcoidosis patients were not significantly different from the results in the young patients (P > 0.05).

Some of the features of both younger and older sarcoidosis patients are compared in Table 2. The older patient group had a greater percentage of females than the younger patients (P = 0.015). Older patients had more frequent extrapulmonary involvement than the others (P < 0.001). However, arthritis or arthralgia (P < 0.001), Lofgren syndrome (P < 0.001), erythema nodosum (P < 0.001) and uveitis (P = 0.006) were less frequent in the older patient population. Steroid therapy was administered to 68 (67%) of the older sarcoidosis patients who had advanced stage (II, III) disease or extrapulmonary involvement at the time of initial diagnosis. Within the study period, no sarcoidosis-related deaths occurred.

Discussion

Although there are some series and case reports focusing on older sarcoidosis patients, there are only a few studies comparing the clinical features of these patients with those of younger subjects. (2,4) A recent study reported that the clinical features of sarcoidosis patients older than 50 years of age were similar to the features of other patients. (2)

In our study, 17.7% of all sarcoidosis patients were more than 50 years of age. Two series from western Europe (5,6) found frequencies similar to this, 11.5% and 13% respectively. However, in a study from the United States, (2) almost half of the patients were older than 50 years of age at the time of initial diagnosis. Genetic and environmental factors probably affect the presentation age of the disease.

Although the distribution of sex in different sarcoidosis series is variable, there is generally a female predominance. (7,8) In our study there was a predominance of females, specifically among older patients; however, there was no such data in the literature.

Our study revealed no difference between older and younger sarcoidosis patients in their distribution among the stages of disease. One previous series (9) reported that older patients had slightly more advanced disease at initial diagnosis. A recently reported series found no differences in presentation and clinical findings. (2) The results of more studies are needed to reach a more certain conclusion on this point.

The frequency of patients with extrapulmonary involvement was significantly higher among our older sarcoidosis patients. Contrary to our results, in the series of Contant et al, (4) extrathoracic findings were infrequently observed in older patients. In addition, some extrapulmonary findings--such as uveitis and arthritis or arthralgia--were quite rare in the older sarcoidosis patient population. Erythema nodosum was also quite infrequently encountered in older patients. (10) Presentation in the form of acute sarcoidosis--Lofgren syndrome--was not frequent in our older patients. It is known that presentation in the form of Lofgren syndrome is usually seen in young females and carries a good prognosis. (10,11) The lower frequency of good prognostic factors like erythema nodosum and Lofgren syndrome in older sarcoidosis patients might point out the presence of more severe and progressive disease in these subjects.

Mantoux test, which is mostly negative in sarcoidosis, was positive at a frequency of nearly 30% in both our older and younger sarcoidosis patients. We think it notable that the Mantoux test yielded results at a certain frequency in all age groups here in Turkey, where tuberculosis is frequent. As a result, the positivity of this test should not lead us to exclude the diagnosis of sarcoidosis in areas where tuberculosis is common.

Uveitis was also less frequent in our older patients. In one report (12) it is stated that ocular sarcoidosis was more frequently diagnosed in young female patients. Although some series (4) reported an increased incidence of malignancy among older patients, none of our patients had malignancy.

Conclusion

We observed that our sarcoidosis patients who were more than 50 years of age had more frequent extrapulmonary involvement and had clinical presentation in the form of Lofgren syndrome only rarely. Our study was retrospective, and therefore provided insufficient data concerning the outcome of the patients. However, we should be more careful in the follow up of older sarcoidosis patients, because they have more frequent extrapulmonary symptoms and fewer good prognostic parameters, like erythema nodosum and Lofgren syndrome. More clinical studies need to be performed to evaluate sarcoidosis patients diagnosed at an older age, and to determine whether diagnostic and therapeutic approaches to this patient population should differ.

Table 1. The various diagnostic methods by which tissues for histologic
examination were obtained in older sarcoidosis patients

Diagnostic methods            n

Transbronchial biopsy         44
Skin biopsy                   19
Mediastinoscopic biopsy       16
Peripheral lymph node biopsy  13
Liver biopsy                   4
Thoracotomy                    2
Lacrimal gland biopsy          2
Parotid gland biopsy           2

Table 2. Comparison of the clinical features of older sarcoidosis
patients to those of other patients (a)

                        Older
                        patients            Younger
                        (> 50)              patients             P

n                       102                 474
Female                   79 (77.5) (b)      308 (65)               0.015
Female/Male               3.43                1.85
Age
  (mean [+ or -] SD)     56.4 [+ or -] 5.7   42.9 [+ or -] 14.4
  (range)               (50-70)              (6-49)
Stage 0 + 1 at
  diagnosis, n (%)       60 (58.8)          289 (61)             NS
Stage II + III at
  diagnosis, n (%)       42 (41.2)          185 (39)             NS
Kveim test positivity,
  n (%) (c)              35 (70)            192 (77.7)           NS
Mantoux test
  positivity, (d)
  n (%)                  31 (30.4)          139 (29.3)           NS
Extrapulmonary inv.,
  n (%)                  78 (76.5)          202 (46.5)           < 0.001
Erythema nodosum, n
  (%)                     8 (7.8)           125 (26.4)           < 0.001
Arthritis or
  arthralgia, n (%)       2 (2)              86 (18.1)           < 0.001
Lofgren syndrome, n
  (%)                     2 (2)              98 (20.7)           < 0.001
Cutaneous involvement,
  n (%)                  26 (25.5)          154 (32.5)           NS
Uveitis, n (%)            2 (2)              47 (9.9)              0.006
Lacrimal gland inv.,
  n (%)                   2 (2)               7 (1.5)            NS

(a) NS, not significant.
(b) Results are n (%) unless otherwise noted.
(c) In the older age group, Kveim test was performed in 50 patients; in
other sarcoidosis patients, it was performed in 247 patients.
(d) Mantoux test was performed in all sarcoidosis patients of older age
and it was available in 449 of the other sarcoidosis patients.

Accepted December 8, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9705-0472

References

1. Merten DF, Kirks DR, Grossman H. Pulmonary sarcoidosis in childhood. AJR 1980;135:673-639.

2. Lenner R, Schilero GJ, Padilla ML, et al. Sarcoidosis presenting in patients older than 50 years. Sarcoidosis Vasc Diffuse Lung Dis 2002; 19:143-147.

3. De Remee RA. The roentgenographic staging of sarcoidosis. Historic and contemporary perspectives. Chest 1983;1:128-133.

4. Conant EF, Glickstein MF, Mahar P. et al. Pulmonary sarcoidosis in the older patient: conventional radiographic features. Radiology 1988; 169:315-319.

5. Loddenkemper R, Kloppenborg A, Schoenfeld N, et al. (WATL Study Group). Clinical findings in 715 patients with newly detected pulmonary sarcoidosis--results of a cooperative study in former West Germany and Switzerland. Sarcoidosis Vasc Diffuse Lung Dis 1998;15:178-182.

6. Romer FK, Hommelgaard P, Schou G. Sarcoidosis and cancer revisited: a long term follow-up study of 555 Danish sarcoidosis patients. Eur Respir J 1998; 12:906-912.

7. Milman N, Selroos O. Pulmonary sarcoidosis in the Nordic countries 1950-1982; epidemiology and clinical picture. Sarcoidosis 1990;7:50-57.

8. Pietinalho A, Hiraga Y, Hosoda Y, et al. The frequency of sarcoidosis in Finland and Hokkaido, Japan: a comparative epidemiological study. Sarcoidosis 1995;12:61-67.

9. Hillerdal G, Nou E, Osterman K, et al. Sarcoidosis: epidemiology and prognosis. Am Rev Respir Dis 1984;130:29-32.

10. Hunninghake GW, Costabel U, Ando M, et al. Statement on sarcoidosis. Am J Respir Crit Care Med 1999;160:736-755.

11. Mana J, Gomez-Vaquero C, Montero A, et al. Lofgren's syndrome revisited: a study of 186 patients. Am J Med 1999; 107:240-245.

12. Faller M, Purohit A. Kennel N, et al. Systemic sarcoidosis initially presenting as an orbital tumour. Eur Respir J 1995;8:474-476.

RELATED ARTICLE: Key Points

* The frequency of advanced-stage disease at the time of initial diagnosis did not differ between young sarcoidosis patients and patients diagnosed when they were more than 50 years of age.

* Clinical presentation in the form of acute sarcoidosis--Lofgren syndrome-is rarely encountered in older patients.

* Erythema nodosum is a skin lesion associated with sarcoidosis, but it is not commonly seen in older patients.

* Uveitis is a feature of sarcoidosis patients diagnosed at younger ages.

Halil Yanardag, MD, and Omer Nuri Pamuk, MD

From the Department of Lung Diseases, Cerrahpasa Medical Facility, University of Istanbul, Istanbul, Turkey, and the Department of Rheumatology, Trakya Medical Faculty, University of Trakya, Edirne, Turkey.

Reprint requests to Halil Yanardag, MD, Istanbul Universitesi, Cerrahpasa Tip Fakultesi, Ic Hastaliklari Ana Bilim Dali, Akciger Hastaliklari Bolumu, Aksaray, Istanbul, Turkey. Email: [e-mail]