Manifestations of sarcoidosis: Analysis of 145 patients, with a review of nine series selected from the literature

doi:10.1016/0002-9343(63)90165-7

The American Journal of Medicine

Volume 35, Issue 1, July 1963, Pages 67-89

https://doi.org/10.1016/0002-9343(63)90165-7 Get rights and content

Abstract

One hundred and forty-five patients with proved generalized sarcoidosis are described. The findings in these patients are compared with those of nine other selected series of proved cases from the literature, and the incidence of the various manifestations determined in the combined group of 1,254 patients.

Differing from other series were such findings in our patients as alopecia and pigmentary skin changes, a relatively high incidence of mild nervous system and joint involvement, two instances of association with lupus erythematosus, and five familial cases.

Although the onset of the disease was usually in the third decade, patients with symptoms beginning as early as age seven years and as late as age seventy-four years were observed by us. In our series 43 per cent of the patients had symptoms of a systemic nature, including fever and weight loss when the disease was active.

In the combined series, the lungs and mediastinal lymph nodes were most frequently involved (94 per cent), with the peripheral lymph nodes next in frequency (73 per cent). The other organs most commonly involved were skin (32 per cent), eye (21 per cent), liver (21 per cent), spleen (18 per cent), bone (14 per cent), salivary glands (6.1 per cent), joints (5.7 per cent), heart (5.1 per cent), nervous system (5.1 per cent) and kidneys (4.3 per cent). All other organs except the bronchi, parathyroid and ovary were found to be infrequently affected, including one case of suspected adrenal involvement seen by us.

Laboratory findings noted were leukopenia (31 per cent), anemia (31 per cent), eosinophilia (25 per cent), thrombocytopenia (1.9 per cent), increased erythrocyte sedimentation rate (61 per cent), decreased serum albumin (37 per cent), increased serum globulin (47 per cent), hypercalcemia (17 per cent), abnormal reactions to serologic tests for syphilis (14 per cent), increased serum alkaline phosphatase (35 per cent) and decreased skin reactions of the delayed type.

In our series and in the combined group, the incidence of sarcoidosis was much higher in Negro subjects than in white. Of our patients females had a higher incidence than males; thus almost half of our patients were Negro females.

The race and sex incidence of each manifestation in our patients was compared to the racesex distribution of our group as a whole. No statistically significant difference in sarcoid manifestations was found primarily due to sex or race except for a higher incidence of hypoalbuminemia and hyperglobulinemia in Negro subjects.

The mortality for the combined series was 3.4 per cent from the disease itself and 1.2 per cent from tuberculosis; however, the follow-up periods were often short.

Marked differences in the incidence of the various manifestations were noted between series, but analysis of the source of patient material explained many of them. Other factors producing differences between the various series reviewed are discussed.

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Recurrent Heerfordt-Waldenström Syndrome with thyroid and meningeal involvement in a Chinese woman
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Sarcoidosis is a multisystem granulomatous disorder of unknown etiology, manifesting with bilateral hilar adenopathy, pulmonary reticular opacities, skin, joint or eye lesions. Heerfordt-Waldenström Syndrome – a constellation of facial palsy, fever, uveitis and parotitis – is a rare presentation of this disorder.
A 47-year-old Chinese woman presented with unintentional weight loss, lethargy with mediastinal and hilar lymphadenopathy. Biopsy of the right paratracheal lymph node via mediastinoscopy showed mycobacterial granulomatous lymphadenitis consistent with tuberculosis with several acid-fast bacilli identified. Lymphoproliferative disorder was ruled out.
She was started on treatment for tuberculosis. Eleven weeks into treatment, she developed a right facial palsy accompanied with fever, uveitis and occipital headache. At this juncture, further history revealed a background of recurrent alternating facial palsy and parotid gland enlargement which was treated for Bell's palsy by three different doctors. New nodules appeared in the left lobe of the thyroid gland. Biopsy of a palpable thyroid nodule and a right supraclavicular lymph nodule showed histological features suggestive of sarcoidosis. Fungal and mycobacterial infections were ruled out. In addition, examination of her cerebral spinal fluid showed lymphocytic inflammation. The serum ACE level was not raised.
A diagnosis of sarcoidosis with incomplete features of Heerfordt-Waldenström Syndrome along with thyroid and meningeal involvement was made. The patient was commenced on prednisolone and azathioprine and her symptoms responded shortly after.
We present a rare case of Heerfordt-Waldenström Syndrome with thyroid and meningeal involvement in a Chinese woman.
Pulmonary sarcoidosis: A comprehensive review: Past to present
2023, Journal of Autoimmunity
Sarcoidosis is a sterile non-necrotizing granulomatous disease without known causes that can involve multiple organs with a predilection for the lung and thoracic lymph nodes. Worldwide it is estimated to affect 2–160/100,000 people and has a mortality rate over 5 years of approximately 7%. For sarcoidosis patients, the cause of death is due to sarcoid in 60% of the cases, of which up to 80% are from advanced cardiopulmonary failure (pulmonary hypertension and respiratory microbial infections) in all races except in Japan were greater than 70% of the sarcoidosis deaths are due to cardiac sarcoidosis.
Scadding stages for pulmonary sarcoidosis associates with clinical outcomes. Stages I and II have radiographic remission in approximately 30%–80% of cases. Stage III only has a 10%–40% chance of resolution, while stage IV has no change of resolution. Up to 40% of pulmonary sarcoidosis patients progress to stage IV disease with lung parenchyma fibroplasia, bronchiectasis with hilar retraction and fibrocystic disease. These patients are at highest risk for the development of precapillary pulmonary hypertension, which may occur in up to 70% of these patients. Sarcoid patients with pre-capillary pulmonary hypertension can respond to targeted pulmonary arterial hypertension medications. Stage IV fibrocytic sarcoidosis with significant pulmonary physiologic impairment, >20% fibrosis on HRCT or pre-capillary pulmonary hypertension have the highest risk of mortality, which can be >40% at 5-years.
First line treatment for patients who are symptomatic (cough and dyspnea) with parenchymal infiltrates and abnormal pulmonary function testing (PFT) is oral glucocorticoids, such as prednisone with a typical starting dose of 20–40 mg daily for 2 weeks to 2 months. Prednisone can be tapered over 6–18 months if symptoms, spirometry, PFTs, and radiographs improve. Prolonged prednisone may be required to stabilize disease. Patients requiring prolonged prednisone ≥10 mg/day or those with adverse effects due to glucocorticoids may be prescribed second and third line treatements. Second and third line treatments include immunosuppressive agents (e.g., methotrexate and azathioprine) and anti-tumor necrosis factor (TNF) medication; respectively. Effective treatments for advanced fibrocystic pulmonary disease are being explored. Despite different treatments, relapse rates range from 13% to 75% depending on the stage of sarcoid, number of organs involved, socioeconomic status, and geography.
The mortality rate for sarcoidosis over a 5 year follow up is approximately 7%. Unfortunately, 10%–40% of patients with sarcoidosis develop progressive pulmonary disease, and >60% of deaths resulting from sarcoidosis are due to advance cardiopulmonary disease. Oral glucocorticoids are the first line treatment, while methotrexate and azathioprine are considered second and anti-TNF agents are third line treatments that are used solely or as glucocorticoid sparing agents for symptomatic extrapulmonary or pulmonary sarcoidosis with infiltrates on chest radiographs and abnormal PFT. Relapse rates have ranged from 13% to 75% depending on the population studied.
Sarcoidosis presenting as thyromegaly
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The relationship between erythema nodosum and prognosis in systemic sarcoidosis: a retrospective cohort study
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Erythema Nodosum (EN) is the most common skin manifestation in sarcoidosis and has often been associated with a good prognosis.
To compare the clinical characteristics and treatment-related features in patients with sarcoidosis according to whether or not EN was seen as a presenting symptom at the time of diagnosis.
A 20-year single-center retrospective study was performed. The following two groups were identified: one group with EN as one of the presenting symptoms at the time of diagnosis of sarcoidosis (EN group) and a second group without EN as a presenting symptom at diagnosis (non-EN group). The clinical characteristics and treatment modalities were collected from the medical records.
A total of 122 patients (31 in the EN group, 91 in the non-EN group) were included. Radiological stages of pulmonary disease were significantly lower in the EN group. Articular involvement was more common in the EN group (p = 0.001), whereas other systemic organ involvements (p = 0.025), especially neurological involvement (p = 0.036), were significantly more common in the non-EN group. In the EN group, a higher percentage of patients were managed without systemic therapy (71.0% vs. 54.9%) and spontaneous remission was more frequent (25.0% vs. 14.1%), however, this wasn’t statistically significant.
Retrospective design.
The lower radiological stage of pulmonary sarcoidosis and lower frequency of systemic organ involvement in patients with EN augment the prognostic value of EN highlighted in the literature. However, this study couldn’t confirm that the patients with EN would need less systemic therapy in the course of their disease.
Atypical and uncommon presentation of sarcoidosis with long segment involvement of the pharynx and larynx: Case report and review of literature
2022, Radiology Case Reports
Pharynx/Larynx is an uncommon site of involvement of sarcoidosis. Isolated pharyngo-laryngeal sarcoidosis is extremely rare as most of the cases are part from multiorgan and systemic sarcoidosis. Pharyngo-laryngeal sarcoidosis is usually asymptomatic which could be attributed to its rare incidence as many cases pass unnoticed. Symptomatic cases usually present with hoarseness of voice. As the disease progress, the patient can present with progressive dysphagia to solid and liquid with globus sensation. We described an atypical involvement of almost the whole length of the pharynx with extension into the larynx in a 51-year-old woman who presented with progressive dysphagia. To the best of our knowledge, this is the first report to describe the imaging features of sarcoidosis involvement of the pharynx and larynx.

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^☆: This study was supported in part by the Pennsylvania Tuberculosis and Health Society.

¹: From the Pulmonary Disease Section, Department of Medicine, Hospital of the University of Pennsylvania and the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

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ReviewManifestations of sarcoidosis: Analysis of 145 patients, with a review of nine series selected from the literature☆

Abstract

J. Invest. Dermat.

Am. J. Med.

Am. J. Med.

New England J. Med.

New England J. Med.

Case of Mortimer's malady (lupus vulgaris multiplex non-ulcerans et non-serpiginosus)

Arch. Surg. (London)

Illustrations of Clinical Surgery

Lupus pernio de la face: synovites fangeuses (scrofulo tuberculeuses) symmetriques des extremities superieures

Ann. dermat. et syph.

Multiple benign sarcoid of skin

J. Cutaneous & Genitourinary Dis.

Local injections of hydrocortisone and cortisone into skin lesions of sarcoidosis

J. A. M. A.

Sarcoidosis and pregnancy

J. A. M. A.

Induction of allergic contact dermatitis in patients with sarcoidosis

Passive transfer of tuberculin sensitivity to patients with sarcoidosis

New England J. Med.

Boeck's sarcoid and systemic sarcoidosis (Besnier-Boeck-Schaumann disease). A study of thirty-five cases

Am. Rev. Tuberc.

Boeck's sarcoid and systemic sarcoidosis (Besnier-Boeck-Schaumann disease). A study of thirty-five cases

Am. Rev. Tuberc.

Sarcoidosis. A clinical and roentgenologic study of twenty-eight proved cases

Arch. Int. Med.

Sarcoidosis. A clinicopathologic review of three hundred cases, including twenty-two autopsies

Am. J. Clin. Path.

A study of sarcoidosis. Based on a combined investigation of one hundred and sixty cases including thirty autopsies from the Johns Hopkins Hospital and Massachusetts General Hospital

Medicine

Sarcoidosis: with special reference to diagnosis and prognosis

Quart. J. Med.

Diagnosis and treatment of sarcoidosis

Brit. M. J.

Sarcoidosis. Study of twenty-nine cases, with a review of splenic, hepatic, mucous membrane, retinal and joint manifestations

Arch. Int. Med.

Review
Manifestations of sarcoidosis: Analysis of 145 patients, with a review of nine series selected from the literature☆