Clinical characteristics of patients in a case control study of sarcoidosis.

Sarcoidosis may be affected by sex, race, and age. A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled 736 patients with sarcoidosis within 6 mo of diagnosis from 10 clinical centers in the United States. Using the ACCESS sarcoidosis assessment system, we determined organ involvement for the whole group and for subgroups differentiated by sex, race, and age (less than 40 yr or 40 yr and older). The study population was heterogeneous in terms of race (53% white, 44% black), sex (64% female, 36% male), and age (46% < 40 yr old, 54% > or = 40 yr old). Women were more likely to have eye and neurologic involvement (chi(2) = 4.74, p < 0.05 and chi(2) = 4.60, p < 0.05 respectively), have erythema nodosum (chi(2) = 7.28, p < 0.01), and to be age 40 yr or over (chi(2) = 6.07, p < 0.02) whereas men were more likely to be hypercalcemic (chi(2) = 7.38, p < 0.01). Black subjects were more likely to have skin involvement other than erythema nodosum (chi(2) = 5.47, p < 0.05), and eye (chi(2) = 13.8, p < 0.0001), liver (chi(2) = 23.3, p < 0.0001), bone marrow (chi(2) = 18.8, p < 0.001), and extrathoracic lymph node involvement (chi(2) = 7.21, p < 0.01). We conclude that the initial presentation of sarcoidosis is related to sex, race, and age.

The clinical management of sarcoidosis. A 50-year experience at the Johns Hopkins Hospital.

Sarcoidosis is an enigmatic disease with extremely variable manifestations in pattern, severity and course. Since Longcope and Freiman's descriptive monograph in 1952 (50) summarizing the clinical findings of the first half of this century, new dimensions of assessing the disease and treatment have been added. The impact of corticosteroids is central. The present review extends the studies to the second half of this century. Earlier diagnosis is facilitated and treatment often reverses many of the disease manifestations and improves the quality and extent of life for the patient. The management issues and guidelines outlined in this paper for both intrathoracic and extrathoracic disease are based on several longitudinal studies of the sarcoidosis patients summarized here, and 50 years of clinical experience by the senior author (CJJ) at Johns Hopkins Hospital, a tertiary referral center with an active Sarcoid Clinic. Case reports are presented in the appendix. It is clear that corticosteroids are the most effective therapeutic agent for sarcoidosis, usually with impressive and prompt response. This represents the dramatic difference in this disease after 1950. No more specific or effective immunosuppressive or antiinflammatory agents have been identified. Undesirable side effects are minimal if excessive doses are avoided. The effectiveness of "steroid-sparing agents" such as methotrexate is uncertain. Although irreversible tissue damage from the disease may limit the effectiveness of treatment, benefits of corticosteroids greatly exceed the negative side effects. Since spontaneous remissions without treatment do occur, a period of observation of 2 years are more is warranted if the patient is relatively asymptomatic. Gradual radiographic progression for 2 or more years, even without major symptoms or reduction in pulmonary function, indicates the need for a trial of corticosteroid treatment, especially in white patients where symptoms may lag behind the radiographic changes. Relapses as treatment is withdrawn are frequent, especially in African-American patients, who tend to have more severe and more prolonged disease than white patients. A minimum of 1 year of treatment is recommended unless no improvement is noted after 3 months. Continued low-dose prednisone at daily doses of 10-15 mg is helpful in preventing relapses and further progression of disease. Periodic attempts at tapering are justified. Repeated relapses may indicate the need for life-long treatment. When irreversible changes are present, especially in the presence of chronic fibrotic disease, changing goals of treatment to provide optimal supportive care may represent better management than having unrealistic expectations from increased corticosteroid dosage or the addition of other potentially toxic immunosuppressive agents. Many agents related to sarcoidosis require further research. The most important question facing sarcoid researchers today is etiology. It is difficult to design specific therapy when the fundamental causes and disease mechanisms are not established. Rather than being a single disease with a single cause, it is possible that a number of genetic factors and environmental or infectious agents may result in an immune response that is manifested as sarcoidosis. Understanding basic causal mechanisms may help explain the varied disease manifestations and aid in designing curative treatments. Such etiologic questions should be explored from both a basic science and an epidemiologic approach. Therapeutic trials of new drugs such as pentoxyfylline and possibly thalidomide are needed to address their potential as well as limitations of steroid therapy. Finally, for patients who have progressed to organ failure, the problems of sarcoid recurrence in transplanted tissue, increased allograft rejection, and long-term prognosis of solid organ transplants have yet to be resolved. (ABSTRACT TRUNCATED)

Sarcoidosis and common variable immunodeficiency. Report of 8 cases and review of the literature.

The true incidence of sarcoidosis in common variable immunodeficiency (CVID) is unknown. We report here 8 cases of sarcoidosis among 80 patients with CVID followed in our clinics, along with 22 well-documented cases reported in the literature. Sarcoidosis, therefore, represents an important entity to consider among patients with CVID who exhibit clinical, radiographic, laboratory, and biopsy findings compatible with sarcoidosis. Conversely, the diagnosis of CVID should be considered in patients with sarcoidosis who do not exhibit the characteristic hypergammaglobulinemia and who have a history of recurrent infections. Although many features of sarcoidosis are similar in patients with CVID to those in patients with sarcoidosis alone, there are many important differences. Patients with CVID in whom sarcoidosis develops present with hypogammaglobulinemia rather than hypergammaglobulinemia and have a higher prevalence of recurrent infections, thrombocytopenia, and splenic involvement. Steroids, in most cases, appeared helpful in reducing adenopathy and splenomegaly, improving uveitis, lowering serum alkaline phosphatase, and reversing hematologic abnormalities. The underlying pathophysiology responsible for the association of these 2 disorders in the same patient remains obscure. However, as more patients are identified, it may be possible to gain a better understanding of the immunologic defect responsible for the dual presentation of these 2 relatively uncommon diseases.

Woman, M.D.: issues, perceptions and choices.

I would end with some summarizing points and questions. 1. A majority of women identify gender-related issues influencing their career choices and pathways. 2. Women are diverse in their choices and priorities, with varying balances of personal and professional life. 3. Eighty-three percent of the women responding to the survey have married, and 82% of those married have children. They thus are likely to have two sets of seriously competing responsibilities. 4. It is possible to identify especially promising women during residency or fellowship. Exploring their priorities and values with good mentors will be important to avoid short-changing academic medicine of competent women. 5. Men and women need to be SUPERCHOOSERS in making the choices right for that individual, rather than superwomen or supermen. 6. We can question whether the development and potential of women (and some men) in academic medicine could be enhanced by: a. Consideration of guidance or support for child care resources? b. Flexibility in the system (tenure clock, etc.)? c. Identification of limited full-time clinical or research opportunities for faculty with young children or unusual family demands? d. Facilitation of bridging after a period of part-time activity or re-entry after limited participation? e. Consideration of part-time work at home and flexible on-site work hours for periods of special family demands? Finally, a supportive work environment is important for both men and women in medicine and is an essential priority in academic medicine. Medicine is a wonderful field. Academic medicine on my terms, to include family, has been very rewarding. Sometimes there also have been disappointments, in that I have fallen short of some of my aspirations. However, I must accept the responsibility for my choices. I owe a great debt to many of the men and women of the American Clinical and Climatological Association and of Johns Hopkins who are both friends and colleagues and especially to my husband, Dick Johns. After 42 years of marriage, I am still learning about the balance of personal and professional life. May we all be Superchoosers!

Flexible transbronchial needle aspiration for the diagnosis of sarcoidosis.

To determine the value of transbronchial needle aspiration biopsy in the diagnosis of sarcoidosis, we reviewed a 1-year experience of consecutive patients with sarcoidosis presenting with hilar and/or paratracheal adenopathy. The sensitivity of transbronchial needle aspiration biopsy in obtaining specimens of noncaseating granulomas was 90%. This yield exceeds that of most published reports of transbronchial lung biopsy and bronchial mucosal biopsy and suggests that transbronchial needle aspiration biopsy may be a valuable diagnostic tool in the evaluation of these forms of sarcoidosis.

Sarcoidosis.

Sarcoidosis continues to be a disease defined descriptively rather than by etiology. Bronchoalveolar lavage has brought new understandings of the pulmonary inflammatory process and its pathogenesis and defects in immunoregulation. Much is known of the clinical characteristics of sarcoidosis, its diagnosis and management. Spontaneous remissions are common, but when treatment is required, the response to corticosteroids is often dramatic, although long-term treatment may be required. The appropriate use of corticosteroids is discussed fully, as are special clinical problems.

Neurosarcoidosis: cerebrospinal fluid lymphocyte subpopulations.

CSF lymphocyte subpopulations of eight patients with neurosarcoidosis were examined. CSF or CT was abnormal in all. The CSF T4/T8 (helper/suppressor) ratio was elevated at 6.8 and 7.6 in two patients; in one, there were only CSF T4 cells. The ratio was normal in five patients.

Neurosarcoidosis: the long-term clinical course.

We reviewed 25 patients with neurosarcoidosis followed for at least 5 years or until death. Seventeen patients (68%) had a monophasic illness. Eight (32%) had a relapsing course, with recurrences similar to the original manifestations months later. Patients with cerebral manifestations or hydrocephalus were most likely to relapse. Seven of eight patients with relapsing disease had exacerbations while taking 10 mg prednisone or less.

Typical and atypical CT manifestations of pulmonary sarcoidosis.

Chest CT of 36 patients with proven sarcoidosis were reviewed retrospectively. In all cases CT was obtained in an attempt to answer a diagnostic dilemma, either a patient with abnormal chest radiography and no clinical diagnosis or a patient with a history of known sarcoidosis and an atypical presentation on chest radiography. Computed tomography was superior to chest radiography in detecting and defining the presence of adenopathy. In addition, CT was more accurate in detecting the presence and extent of infiltrates. Secondary findings in sarcoidosis including pleural effusions, bullous disease, bronchiectasis, cavitation with and without mycetoma, and fibrosing mediastinitis were detected using CT. Using the information obtained from CT, we were able to arrive at the correct diagnosis in the majority of cases and to decide which modality would be most useful to secure tissue confirmation (bronchoscopy, transtracheal biopsy, or percutaneous needle biopsy of a solitary mass).

Ocular involvement in chronic sarcoidosis.

Although spontaneous remissions often occur in sarcoidosis, chronic persistent disabling disease is also observed. Of a series of 183 patients with chronic sarcoidosis, 47 (26%) had ophthalmic involvement. In this series, chronic sarcoid was defined as disease for a minimum of five years. Patients were followed primarily for their systemic disease for a mean of 13 years. Uveitis developed in 35 patients (19%) and was an early manifestation in 32 (91%). The course of the ocular disease did not necessarily parallel that of the systemic disease. Despite the chronic nature of the underlying disease, the anterior uveitis did not pursue a chronic course in 15 of 33 patients (45%) and was generally characterized by a single episode at the onset of disease. Chronic uveitis and secondary glaucoma were poor prognostic signs, as eight of 11 patients with uveitis and glaucoma suffered severe visual loss.

Longitudinal study of chronic sarcoidosis with low-dose maintenance corticosteroid therapy. Outcome and complications.

A series of 181 patients with chronic persistent sarcoidosis for more than 5 years have been reviewed, with a mean follow-up period of 14 years, and 77% followed for more than 10 years. Efforts to identify more white patients meeting the criteria of such persistent disease were unsuccessful. Seventy-eight percent were black, and 69% were women. Pulmonary disease was the major manifestation in 70% and was present in 88%. The early major disease feature predicts the nature of the long-term manifestation in 94%. Ninety-four percent were treated with prednisone, with 63% for more than 5 years. Fifty-three percent required continued treatment, and of those receiving continued treatment, 91% were maintained on doses of no more than 15 mg daily and 65% on no more than 10 mg of prednisone daily. Relapses were frequent as prednisone was withdrawn, occurring at least once in 75% and several times in 51%. Low-dose prednisone treatment with 5-15 mg daily provides significant benefit. A mean treatment period of 8 years was observed (range: 10 days to 24 years). The benefits of treatment greatly exceed the infrequent complications. In Baltimore, chronic sarcoidosis with persistent disease seems to be more frequently encountered in black patients than in white patients.

The longitudinal study of chronic sarcoidosis.

Although spontaneous remissions are frequent in sarcoidosis, chronic persistent disabling disease is also observed. This feature seems more frequent and more severe in black patients, as has been previously reported (10). The more extensive and severe the initial disease manifestations, the more likely it is that the disease will continue. Corticosteroids are usually beneficial and complications are infrequent. Delayed or interrupted treatment seems to allow progression or irreversible disease or both. Patient compliance is an obvious important factor. Relapses are frequent as treatment is withdrawn but are usually at least partially reversible. Some deterioration is observed with repeated relapses. Low dose daily prednisone (5-15 mg) seems to prevent relapses. Patient compliance is facilitated with daily treatment rather than alternate day therapy. Prolonged treatment for 10 to 15 or more years is often required. Chloroquine is particularly helpful in skin and mucosal disease. The necessity for long-term thoughtful management is obvious.

Mycetomas in pulmonary sarcoidosis: non-surgical management.

The course and prognosis of all patients with mycetomas in the setting of pulmonary sarcoidosis from 1960 to 1978 were reviewed. Twelve patients were identified. All patients were managed conservatively without surgery or antifungal agents. Three patients died; however, only one death could be attributed to the presence of a mycetoma and all deaths were associated with severe pulmonary insufficiency. Episodes of both major and minor hemoptysis were managed successfully with supportive therapy alone in the remaining nine patients. Survival after the diagnosis of a mycetoma was 10-14 years in three patients, 5-7 years in three patients and 3-4 years in three patients. All nine surviving patients have required corticosteroids for control of their underlying sarcoidosis. Extracavitary invasive disease due to Aspergillus organisms was not seen in this group. In the setting of chronic pulmonary sarcoidosis with mycetoma formation, fatal hemoptysis is infrequent and episodes of hemorrhage may be safely managed with supportive medical therapy alone.

Low cost ambulatory medical information system.

A simple, low-cost computerized minirecord system (minimal essential record) has been in operation at the Johns Hopkins Medical Clinic since mid-1975. The system has three primary components: (a) the Minirecord which contains a listing of problems and medications, plus information about visits to other clinics, (b) an appointment system used to organize materials prior to clinic encounters and assist in the follow-up of high risk special patients, and (c) an encounter data system to prepare reports used for management, quality assurance and training. This paper describes the system's operation, and reports on its utility and cost.