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Twenty-six symptomatic subjects with clinical evidence plus either high-resolution computed tomography (HRCT, n = 25) or open-lung biopsy (OLB, n = 1) patterns typical for idiopathic usual interstitial pneumonia (idiopathic UIP) were entered into a randomized prospective treatment trial using high-dose prednisone (n = 12) versus colchicine (n = 14). The minimum dose of prednisone used was 60 mg/d for 1 mo, tapered to 40 mg/d over the second month, tapered to 40 mg every other day during the third month, with subsequent doses adjusted as clinically indicated. The dose of colchicine was 0.6-1.2 mg/d, as tolerated. The presence of a rim of subpleural honeycomb change was present in all of the 25 subjects who had HRCT. Subjects treated with high-dose prednisone alone experienced a higher incidence of serious side effects and also exhibited a trend (not statistically significant, p = 0.391) to more rapid decline of pulmonary function and shortened survival than did those treated with colchicine alone. In most subjects with typical clinical and HRCT features of idiopathic UIP, neither prednisone nor colchicine resulted in objective improvement, and the disease continued to progress in the majority. Colchicine appears to be a safer alternative to a trial of high-dose prednisone but may be no different than no therapy.

Objective To attempt to determine whether a relationship exists between carcinoid tumors and sarcoidosis. Material and Methods We present a series of seven case reports and discuss hypotheses about possible disease associations. Results Certain malignant lesions have tended to occur in patients with sarcoidosis. Seven patients who were encountered at Mayo Clinic Rochester between 1950 and 1994 had both sarcoidosis and carcinoid tumors. These patients ranged in age from 31 to 66 years, and three of the patients had a history of benign thyroid disorders. Malignant tumors have been thought to be related to sarcoidosis in one of two ways: (1) immunologic abnormalities in sarcoidosis may promote the development of neoplasms or (2) malignant disease may promote the onset of sarcoidosis either by causing local sarcoid reactions that progress or by directly initiating the manifestations of systemic sarcoidosis. Because the chronology of events differed in our seven cases, various mechanisms of action may have a role in the manifestations of these two disease entities. Our cases emphasize the importance of avoiding the diagnosis of disseminated malignant disease in patients with cancer and associated hilar and mediastinal lymphadenopathy without biopsy confirmation of metastatic disease. Conclusion Application of the knowledge gained about the mechanisms of disease in sarcoidosis will perhaps facilitate identification of the pathogenesis of carcinoid tumors and other neuroendocrine tumors.

Objective To determine the frequency and the types of neurologic involvement in a series of patients with Churg-Strauss syndrome (CSS). Design We reviewed the medical records of 47 consecutive patients with CSS who were examined at the Mayo Clinic between January 1974 and June 1992. Material and Methods The study patients were classified into two groups: (1) those with a histopathologically confirmed diagnosis of CSS who had evidence of either vasculitis or Churg-Strauss granuloma, the presence of asthma, and peripheral eosinophilia (more than 10% eosinophils) on at least one differential leukocyte count (N = 33) and (2) those with a clinical diagnosis of CSS who had evidence of vasculitis based on either multiple mononeuropathy or necrotizing cutaneous lesions, the presence of asthma, and peripheral eosinophilia (more than 10% eosinophils) on at least one differential leukocyte count (N = 14). Results Of the 47 patients, 29 (62%) had neurologic involvement. Peripheral neuropathy was detected in 25 patients: 17 had multiple mononeuropathy, 7 had distal symmetric polyneuropathy, and 1 had an asymmetric polyneuropathy. Three patients had cerebral infarctions. Less commonly identified problems included radiculopathies, ischemic optic neuropathy, and bilateral trigeminal neuropathy. Asthma preceded the onset of neurologic involvement in all cases (mean duration, 6.7 years). Follow-up data, when available, showed that corticosteroid therapy usually yielded improvement or stabilization. Conclusion Neurologic involvement is common in CSS, usually manifesting as peripheral neuropathy. In this series of patients, asthma preceded the neurologic manifestations.

This study was designed to characterize the clinical spectrum and course of tracheobronchial involvement in Wegener's granulomatosis (WG). Of the 51 patients with biopsy-proven WG who underwent bronchoscopy at least once at our institution between January 1982 and November 1993, 30 (59%) had endobronchial abnormalities due to WG. Initial findings included subglottic stenosis in five (17%), ulcerating tracheobronchitis with or without inflammatory pseudotumors in 18 (60%), tracheal or bronchial stenosis without inflammation in four (13%), and hemorrhage without identifiable source in two (4%) patients. Nine patients with ulcerating tracheobronchitis on initial study had subsequent bronchoscopies for continued symptoms, which in seven cases documented the progression from ulcerating tracheobronchitis to stenosis without inflammation. Bronchoscopic interventions included dilation by rigid bronchoscope in three, YAG-laser treatment in one, and placement of silastic airway stents in three patients. Only the stents provided persistent airway patency. Endobronchial biopsies were performed on 21 occasions in 17 patients. Half of the specimens were helpful in establishing the diagnosis and in all but three in assessing disease activity. While antineutrophil cytoplasmic antibody titers reflect overall disease activity, no correlation with endobronchial inflammatory activity was apparent.

Objective To characterize the clinicopathologic spectrum of respiratory tract involvement in patients with positive results of immunofluorescence microscopy for anti-neutrophil cytoplasmic autoantibodies with a perinuclear staining pattern (p-ANCA) and to assess the clinical value of p-ANCA testing. Design We retrospectively reviewed the medical records of all patients at Mayo Clinic Rochester in whom p-ANCA were detected by indirect immunofluorescence microscopy during 1992. Material and Methods Additional target antigen identification was performed with use of enzyme-linked immunosorbent assays for antibodies against myeloperoxidase (MPO) and proteinase 3. We summarized the clinical findings in MPO-positive and MPO-negative patients. Results Sera were positive for p-ANCA in 42 of 2,381 patients (1.8%). In 13 of these 42 patients (31%), the respiratory tract was involved. Twelve patients had chest roentgenographic abnormalities, including a diffuse alveolar filling pattern (N = 8), a diffuse interstitial pattern (N = 2), and a combined interstitial and alveolar pattern (N = 2); three others had nasal inflammation. Ten of 16 sera tested were positive for MPO, and proteinase 3 antibodies were detected in 1 specimen. All patients with alveolar hemorrhage were positive for MPO antibodies. Conclusion Testing for p-ANCA by immunofluorescence microscopy discloses a wide range of clinical disorders distinct from the main cytoplasmic-staining ANCA-associated disease—namely, Wegener's granulomatosis. In particular, the respiratory tract is affected much less frequently. Further evaluation of positive p-ANCA immunofluorescence test results by enzyme-linked immunosorbent assay to determine whether MPO is the target antigen is necessary to obtain clinically useful information from this test.

Progressive dyspnea that developed in a 52-year-old woman with a lifelong history of asthma did not respond to high-dose orally administered glucocorticoids. Initially, a diagnosis of allergic broncho-pulmonary aspergillosis or hypersensitivity pneumonia was suggested as the cause of the worsening dyspnea. Pulmonary function tests demonstrated severe airway obstruction; substantial improvement was noted after bronchodilator therapy. Maximal inspiratory pressure was decreased, and the diffusing capacity of the lungs was abnormal. Computed tomography of the chest showed no parenchymal or mediastinal abnormalities. During a sniff test, fluoroscopy of her diaphragm disclosed paradoxical motion of both hemidiaphragms during inspiration, consistent with bilateral hemidiaphragmatic paralysis. Parsonage-Turner syndrome was diagnosed. The dose of glucocorticoids was tapered. Follow-up of the patient by telephone contact in March 1994 (9 months after her initial examination at our clinic) revealed that the dyspnea was still severe.

Sarcoidosis is a chronic inflammatory disease of unknown cause characterized by the formation of nonnecrotizing granulomas in affected tissues, most notably the lungs. Granuloma healing may result in pulmonary fibrosis and respiratory impairment in some patients. Transforming growth factor-beta 1 (TGF-beta 1) is a potent cytokine that promotes fibrosis by enhancing the synthesis of extracellular matrix components, including fibronectin and the alpha 5 beta 1 fibronectin receptor. The role of TGF-beta 1 in promoting lung fibrosis in the setting of pulmonary sarcoidosis has not yet been investigated. Accordingly, we determined the extent and distribution of TGF-beta 1 in lung tissue obtained from seven patients with clinical and histologic features of pulmonary sarcoidosis. The tissue distributions of TGF-beta 1, the TGF-beta 1 binding proteoglycan decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor were assessed immunohistochemically. In all cases, the epithelioid histiocytes comprising nonnecrotizing granulomas of pulmonary sarcoidosis contained abundant TGF-beta 1. We further demonstrated decorin, fibronectin, and the alpha 5 beta 1 fibronectin receptor within nonnecrotizing granulomas and in the fibrous tissue surrounding the lesions. TGF-beta 1 staining was also observed in bronchiolar epithelial cells, hyperplastic Type II pneumocytes, and occasional alveolar macrophages. This study demonstrates enhanced tissue localization of TGF-beta 1 and related extracellular matrix proteins associated with the nonnecrotizing granulomas of pulmonary sarcoidosis. Through its actions on matrix protein synthesis, TGF-beta 1 may modulate the fibrotic repair process accompanying granuloma healing in sarcoidosis.

Between January 1973 and October 1991 at the Mayo Clinic, 5 of 345 patients with Wegener's granulomatosis initially had features suggestive of giant cell arteritis and subsequently were found to have biopsy-proven vasculitis of the temporal artery. All five patients were older than 60 years of age and had jaw claudication, sudden loss of vision, severe headache with or without diplopia, or polymyalgia rheumatica at the time of initial examination. The erythrocyte sedimentation rate was high at the time of onset of symptoms in four patients (and unavailable in one patient). A temporal artery biopsy specimen revealed giant cell arteritis in one patient and non-giant cell arteritis in four patients. All five patients subsequently had pulmonary and renal lesions characteristic of Wegener's granulomatosis, with typical histopathologic features on biopsy or positive cytoplasmic staining antineutrophil cytoplasmic antibodies. Thus, overlapping features of giant cell arteritis and Wegener's granulomatosis do occur in some patients.

The development of the antineutrophil cytoplasmic autoantibody (ANCA) test has lent support to the concept of Wegener's granulomatosis as a spectrum that may affect one or more of the major anatomic sites: upper respiratory tract (E), lung (L), or kidney (K). It is C-ANCA that has high specificity for Wegener's granulomatosis (WG). The sensitivity is highest in the fully expressed Wegener's triad, or ELK, and less in local regional disease. It is possible that isolated manifestations such as episcleritis, subglottic stricture, or diffuse alveolar hemorrhage associated with C-ANCA may be considered in the Wegener's spectrum, although traditional histopathologic criteria are lacking. Until specific etiologic agents are uncovered for the various ANCA-associated entities, classification schemes should continue to employ previously established clinicopathologic syndromes such as WG using the ANCA test to better define their clinical spectrums.

Wegener's granulomatosis is a multisystem disease often with protean manifestations. Eye signs and symptoms can be prominent and may be the patient's initial complaint. For a definitive diagnosis of Wegener's granulomatosis, a tissue biopsy specimen must show vasculitis and necrotizing granuloma. The presence of anticytoplasmic autoantibodies in the serum of patients has been found to be highly specific for Wegener's granulomatosis and can considerably facilitate early diagnosis and be used to monitor disease activity. In two illustrative cases, the utility of this laboratory test in the differential diagnosis of scleritis and orbital pseudotumor is demonstrated.

Wegener's granulomatosis and the Churg-Strauss syndrome are both syndromes that appear to begin with a phase of regionally limited symptomatology before they progress at unpredictable rate to a generalized phase characterized by symptoms of systemic vasculitis. The clinical features of atopy, peripheral blood eosinophilia, and tissue eosinophilia distinguish CSS from WG, with its typical necrotizing granulomatous respiratory tract lesions. Whereas in generalized WG with renal involvement the use of cyclophosphamide usually cannot be avoided, the generalized systemic vasculitis phase of CSS appears to respond well to glucocorticoids alone. For the more limited forms of WG, adapted therapy regimens including trimethoprim-sulfamethoxazole have been reported to be successful. Anticytoplasmic autoantibodies (c-ANCA = ACPA) are a new diagnostic serum test with high specificity for WG. Serial determinations of c-ANCA are a promising tool to monitor disease activity.

Objective To assess the results with colchicine and prednisone as initial single-drug therapy in patients with usual interstitial pneumonia (UIP). Material and Methods We reviewed the serial pulmonary function test results in 22 patients with typical clinical and high-resolution computed tomographic features of UIP who were treated with colchicine as initial single-agent therapy and compared them with a group of 22 historical patients with UIP of similar severity diagnosed by open-lung biopsy who were given prednisone as initial single-drug therapy. Results No significant difference was detected in the rate of decline of pulmonary function or in the time to "failure" between the two study groups. A trend was suggested for more rapid decline of pulmonary function in the prednisone-treated than in the colchicine-treated group. The design of this study does not allow distinction between a possible beneficial effect of colchicine and a possible adverse effect related to weaning from high-dose prednisone. Colchicine was well tolerated; few side effects other than mild diarrhea were noted in those patients able to take the drug long enough to return for pulmonary function testing at 3 months. In comparison, the side effects of prednisone were more serious and were not always reversible with cessation of therapy. Conclusion This study lends further support to the assumption that colchicine may be a satisfactory and less hazardous substitute for prednisone in the treatment of patients with UIP.

Cyclophosphamide-induced lung toxicity may be difficult to recognize because of the presence of confounding variables such as concomitant use of other cytotoxic drugs, opportunistic infections, diffuse pulmonary malignancy, radiation pneumonitis, and oxygen toxicity. The purpose of this retrospective analysis was to identify the clinical spectrum of pulmonary toxicity of cyclophosphamide. In our review of case records, we sought to identify patients in whom cyclophosphamide was the only identifiable etiologic factor for lung toxicity. In a 20-yr period six patients were identified with cyclophosphamide-induced lung disease, including five men and one woman ranging in age from 42 to 78 yr. Clinical features of toxicity include dyspnea, fever, cough, new parenchymal infiltrates, gas exchange abnormalities on pulmonary function tests, and pleural thickening on chest roentgenogram. Two patterns of cyclophosphamide-induced lung toxicity were identified. A single patient presented with early-onset pneumonitis and responded to discontinuation of the drug. Five patients with late-onset pneumonitis developed progressive pulmonary fibrosis associated with bilateral pleural thickening. Patients with late-onset pneumonitis showed no response to cessation of cyclophosphamide and institution of corticosteroid therapy. Three of these patients died of respiratory failure. Careful review of the individual cases reported in the literature as cyclophosphamide lung toxicity revealed only 12 cases in whom none of the additional confounding factors could be identified. These could easily be divided in the same two categories. Early-onset pneumonitis is reversible and may respond to corticosteroid therapy. Late-onset pneumonitis, frequently associated with pleural thickening, is clinically distinct from idiopathic pulmonary fibrosis but has a chronically progressive course. It appears unresponsive to corticosteroid therapy.

Thirty patients (24 men and 6 women) with a median age of 44.5 years who had angiocentric T-cell lymphoma were studied. The neoplastic cells in each had a T-cell phenotype. Epstein-Barr virus RNA was detected in the neoplastic cells in 29 of 30 patients. The most common presenting symptom was nasal obstruction followed by purulent rhinorrhea. Patients with early presentation had only a friable nasal or nasopharyngeal mucosa ; late clinical signs included septal perforation in 40%. Twenty-one of 30 patients received radiation therapy as initial treatment ; 22 of 30 patients achieved a complete remission. Fifteen patients relapsed : 10 with local recurrence and 5 with systemic disease. In long-term follow-up, 10 patients were alive and disease free, 6 patients died of unrelated causes, and 12 patients died of disease.

Sarcoidosis is a systemic granulomatous process of unknown cause. Pathologically, it is characterized by noncaseous granuloma, and in more than 90% of patients, the lung or intrathoracic lymph nodes are affected. A roentgenographic staging system (stages I, II, and III), based on the appearance of the plain chest roentgenogram, conveys important information about prognosis, degree of symptoms, and pulmonary function abnormalities. The diagnosis should be confirmed by histopathologic examination and exclusion of known causes for the noncaseous granulomatous reaction. When indicated, treatment with alternate-day regimens of prednisone is highly effective. Serial chest roentgenography, pulmonary function studies, and the serum angiotensin-converting enzyme level are useful for monitoring the course of the disease.

Neurological involvement in Wegener's granulomatosis was studied by reviewing the charts of 324 consecutive patients in whom the diagnosis was made at the Mayo Clinic. One hundred nine patients (33.6%) had neurological involvement. Peripheral neuropathy occured in 53; cranial neuropathy, in 21; external ophthalmoplegia, in 16; cerebrovascular events, in 13; seizures, in 10; cerebritis, in 5; and miscellaneous involvement, in 25. The mean age and sex ratio were similar in the patients with and those without neurological involvement. Among the patients with peripheral neuropathy, 42 had mononeuropathy multiplex; 6, distal symmetrical polyneuropathy; and 5, unclassified peripheral neuropathy. Multiple mononeuropathy was a major presenting symptom in 8 patients. A significantly higher percentage of patients with peripheral neuropathy, compared to those without peripheral neuropathy, had kidney involvement (p < 0.001). The second, sixth, and seventh cranial nerves were most frequently affected. Multiple cranial nerves were affected in 8 patients. Unusual neurological manifestations in the miscellaneous group were spastic paraparesis, temporal arteritis, Horner's syndrome, and papilledema.

There is no standard or known optimal treatment for idiopathic pulmonary fibrosis. Corticosteroids have been used with widely variable benefit. Colchicine has been reported to suppress fibroblast growth factors and to inhibit collagen deposition. A potential role has been proposed for colchicine in the treatment of fibrotic pulmonary diseases. We retrospectively assessed the outcome of 23 patients with idiopathic pulmonary fibrosis in whom colchicine was used as empiric treatment. Eighteen patients had received prior corticosteroid therapy. By clinical and pulmonary function criteria, five patients (22 percent) improved following colchicine, nine (39 percent) remained stable, and nine (39 percent) worsened. The average duration of follow-up was 22 months. Despite limitations of this retrospective analysis, colchicine may be of benefit in pulmonary fibrosis and should be considered for further clinical trials.

The clinical spectrum of seventy-six consecutive c-ANCA positive patients is described and its relation to clinical classification schemes for Wegener’s granulomatosis (WG) is investigated. c-ANCA detection by immunofluorescence (IF) is compared to detection by two different ELISA systems.

Before discussing the role of anticytoplasmic autoantibodies (ANCA) in the diagnosis of Wegener’s granulomatosis (WG), it is instructive to consider the subject of nosology in general, which will clarify the usefulness and limitations of various systems of classification.

Review of 411 patients with Wegener’s granulomatosis showed that involvement of the head and neck region is extremely common Early diagnosis and prompt treatment resulted in better survival rates--75% alive at 5.8 years.

Friedrich Wegener was born April 7, 1907, in Varel and died July 9, 1990, in Lubeck. Between these historical brackets is the story of a life worth telling.

• Salivary gland involvement is a rare clinical feature of Wegener's granulomatosis. We report a series of five cases in which submandibular or parotid gland swelling was part of the initial manifestation of the disease. All patients had limited forms of Wegener's granulomatosis. The value of determination of serum anti-neutrophil cytoplasmic autoantibodies is demonstrated in four of the cases, and its use as a new diagnostic adjunct and promising tool to monitor disease activity is discussed. The use of trimethoprim-sulfamethoxazole as part of alternative treatment regimens for limited Wegener's granulomatosis is advocated. ( Arch Otolaryngol Head Neck Surg . 1991;117:218-223)

We reviewed the epidemiologic, laboratory, roentgenographic, pulmonary function, and survival data from 28 patients who had a histologic diagnosis of lymphomatoid granulomatosis (LG) with involvement of the lungs. The mean age at the time of diagnosis was 51 years, and the male-to-female ratio was 3:2. Ten patients had other underlying diseases before LG was diagnosed. The most prominent symptoms were cough, dyspnea, fever, and rash, which were usually present for several months before diagnosis of LG. Multiple nodules were detected on a chest roentgenogram in 68% of the patients. Immunoglobulin concentrations were abnormal in 8 of 12 patients studied. Although bronchoscopy established the diagnosis in approximately a third of the patients who underwent this procedure, open-lung biopsy was uniformly diagnostic. The median survival was 72 months, with follow-up through 12 years. In 11 patients, the original diagnosis of LG was eventually changed to lymphoma. In five of these patients, the change in diagnosis was based on immunohistologic data obtained shortly after LG was discovered. Lymphoma diagnosed in this way was associated with a better prognosis than lymphoma diagnosed on the basis of conventional histopathologic findings. In three patients, solid tumors eventually developed. The diversity of clinical outcomes and frequent revisions of the diagnosis led us to consider the possibility that LG may also represent a histopathologic finding that occurs transiently in several disease processes.

Since its first description by Wegener in 1936, Wegener's granulomatosis has undergone significant changes in terms of clinical scope, diagnosis, and treatment. It is no longer tenable to insist on the fulfillment of the Wegener's triad to make the diagnosis. The wide range of clinical presentations is encompassed by the ELK (ear, nose, and throat; lung; kidney) classification in which any combination or singular involvement of the major sites can be considered within the Wegener's spectrum if supported by the appropriate pathologic findings or the presence of a cytoplasmic antineutrophil cytoplasmic antibody pattern. Treatment is based on the extent of involvement and clinical tempo. Trimethoprim-sulfamethoxazole may be used for patients with localized disease. Systemic disease, including involvement of the kidney, mononeuritis multiplex, and skin vasculitis, is treated with systemic glucocorticoids and cyclophosphamide. Research into the antineutrophil cytoplasmic antibody phenomenon is yielding new insights into possible pathogenic mechanisms.

Many medical treatments are based on sheer empiricism. In 1975 I noted that trimethoprim–sulfamethoxazole had a salutary effect in a woman with Wegener's granulomatosis involving all major sites, i...

For over 25 years, glucocorticoids have been the chief agents used in the treatment of pulmonary sarcoidosis. Most authorities agree that such treatment is effective, but much controversy exists about the indications for administration. Presented herein is a method of treatment using an alternate-day regimen of administration of prednisone; this approach is based on a synthesis of personal experience and findings in the literature.

A review of 52 recent cases of Wegener's granulomatosis has clarified the clinical manifestations and has emphasized the otolaryngologist's role in its early diagnosis. All the cases satisfied the currently accepted criteria for the condition: the presence of primary necrotizing vasculitis in a patient with a typical clinical course. Among the 52 patients, 31 patients had nasal lesions. The typical manifestation was persistent nasal obstruction in a middle-aged patient with no history of nasal disorder. In the early stages, intranasal examination may reveal only diffuse nasal mucosal swelling, without tissue destruction. Systemic symptoms are malaise, night sweats, intermittent pyrexia, and migratory arthralgias; an abnormally high sedimentation rate is also frequent. Later, the typical nasal findings are diffuse destruction of the mucosa and foul-smelling crusts. The tissue underlying the crusts is extremely friable. Perforations of the nasal septum are also common. Adequate biopsy of representative tissue is important. The condition is treatable; currently, corticosteroids with or without cyclophosphamide are being used. Of the 52 patients, 31 are alive; 10 are dead, and current information is unavailable on 11 patients. Polymorphic reticulosis (PMR, lethal midline granuloma, or malignant midline reticulosis) was noted in 16 other patients during the same period. Differentiation between PMR and Wegener's granulomatosis is important because, although they can resemble each other clinically, they are morphologically distinct and respond to different forms of therapy (Wegener's granulomatosis to immunosuppressive drugs and PMR to irradiation). The otolaryngologist has an important role in the early diagnosis of Wegener's granulomatosis because of the high incidence of nasal involvement and because of the variations in clinical manifestations, which depend on the stage of the disease.

We describe two patients with diffuse non-Hodgkin's lymphoma, hypercalcemia, and increased activity of serum angiotensin-converting enzyme. A mechanism similar to that operative in sarcoidosis is speculated to have caused the hypercalcemia. A lymphokine elaborated by the malignant lymphoma may cause activated macrophages to produce 1,25-dihydroxyvitamin D3.

Twelve patients with Wegener's granulomatosis were treated with antimicrobial agents, chiefly trimethoprim-sulfamethoxazole. The clinical course improved in 11 of the 12 patients who received this treatment. The success of antimicrobial treatment suggests the possibility of a microbial infection as the inciting cause of Wegener's granulomatosis in some patients. Alternatively, these agents--in particular, trimethoprim-sulfamethoxazole--may possess immunosuppressant activity.

A population-based study was conducted among residents of Rochester, Minnesota from 1935-1984 to examine the influence of diagnostic access bias on the incidence and mode of presentation of clinically recognized sarcoidosis. Immigrants had an elevated risk of sarcoidosis and were more likely to present with asymptomatic sarcoidosis diagnosed on routine screening chest radiographs. Similar patterns were observed for health professionals, a group with markedly greater access to the diagnostic procedures which label them as having sarcoidosis. Sarcoidosis exhibits a spectrum of manifestations, ranging from a totally asymptomatic process discernible only by specific diagnostic scrutiny to a clinically obvious presentation with significant morbidity. For disease entities such as this, apparent patterns of occurrence may depend on differential access in the study population to the maneuvers necessary for diagnosis. Diagnostic access bias, in addition to other diagnostic biases, deserves more careful scrutiny in epidemiologic research.

Serum angiotensin-converting enzyme (SACE) levels were measured in 44 subjects six weeks after acute pulmonary histoplasmosis. All patients were infected in a common-source outbreak of histoplasmosis which occurred on one day. All patients had both strictly defined clinical and serologic evidence of infection. The SACE activity was elevated at six weeks compared to normal controls, and seven of the 44 had levels more than 2 SD above the normal mean. SACE levels were also measured at three and 24 weeks after acute infection in a smaller number of the same subjects. Serial observations demonstrated that all subjects (including those with normal and elevated SACE at six weeks) had a rise and fall in SACE activity following symptomatic acute pulmonary histoplasmosis. Our findings suggest that elevated SACE does not reliably separate sarcoidosis from histoplasmosis, although elevations in histoplasmosis are much less common and may occur only briefly following acute pulmonary histoplasmosis. More important, it seems that SACE activity rises acutely in all patients with symptomatic acute histoplasmosis and then falls gradually toward baseline over several months, coinciding temporally with the granulomatous response.

The awareness that sarcoidosis can involve intrathoracic lymph nodes and lung parenchyma in sequential fashion evolved during the first half of this century. This awareness resulted in a roentgenographic staging system that has relevance to the course and prognosis, pulmonary function changes, and the symptom of dyspnea. The following definition or roentgenographic staging is proposed as the simplest, most reproducible system based solely on the roentgenographic appearance, avoiding histopathologic and pathophysiologic inferences. Stage I: bilateral hilar lymphadenopathy; stage II: bilateral hilar lymphadenopathy plus parenchymal infiltration; and stage IQ: parenchymal infiltration without bilateral hilar lymphadenopathy. The early data concerning bronchoalveolar lavage, determination of serum angiotensin-converting enzyme, and gallium 67 citrate scanning appear to have no clear relationships to staging, suggesting that staging continues to have unique value to the clinician in the classification of sarcoidosis and in the delineation of its clinical course and prognosis.

Twenty-four patients with sarcoidosis had normal serum angiotensin converting enzyme (SACE) values at time of diagnosis. Sixteen patients were in stage I and eight of these underwent complete remission and four followed a stable course. Seven of eight patients in stages II and III experienced improvement while receiving glucocorticoid treatment. In six, serial SACE measurements fell significantly, paralleling the clinical improvement. The data suggest that a normal SACE in stage I indicates a good prognosis. Patients in stages II and III with normal SACE levels may still have active disease potentially responsive to glucocorticoid treatment. The reduction of SACE while receiving treatment may be viewed as the "suppressible" SACE compartment, representing that portion of the enzyme elaborated by the granuloma or its cellular precursors. The level remaining after suppression by glucocorticoids may be considered "basal" SACE, probably related to normal turnover of SACE producing cells in vascular endothelium.

Allergic granulomatosis is a distinct clinical syndrome occurring in adults with asthma, eosinophilia, and multisystem vasculitis. Atopy and drug sensitivity are other important features. The skin reactions are most commonly nodular and inflammatory lesions. A unique feature is the deep papulonodules, which may occur singly on the scalp or symmetrically on the extremities. Cutaneous findings may range from purpura to urticaria and ulceration. The most common histologic finding is the extravascular granuloma; however, necrotizing vasculitis of small vessels is seen, as well as periarteritis nodosa involving larger vessels of the skin. This varied histologic and clinical spectrum seen in patients with systemic allergic granulomatosis is a reflection of a unique host response to multiple antigens. The cutaneous findings imply that allergic granulomatosis probably represents a unique host response to the same causative and pathogenetic factors as are usually found in periarteritis nodosa and necrotizing vasculitis.

Five patients with Wegner's granulomatosis were found to have significantly raised serum immunoglobulin E (IgE) levels. The rise in IgE was not related to the extent of clinical involvement, was not part of a generalized serum immunoglobulin rise, and was not associated with eosinophilia. Raised serum IgE may be a clue to the pathogenesis of this disease.

• Our experience with 50 patients with Wegener's granulomatosis and 40 patients with polymorphic reticulosis allowed us to compare these two disorders both clinically and histopathologically. Although these conditions are similar in some respects, they are separate and separable entities. The histologic features may be the most useful criteria for differentiation. Wegener's granulomatosis is characterized by the presence of vasculitis and necrotizing granulomas, whereas polymorphic reticulosis is typified by a mixed lymphoid infiltrate with an angiocentric growth pattern. The physician should be aware of the differences between these two disorders and should understand the implications of both conditions. ( Arch Otolaryngol 1981;107:141-144)

140 patients with biopsy-proven Wegener's granulomatosis were examined during a 16-year period at the Mayo Clinic. Forty patients had diverse and explosive ophthalmic involvement, including conjunctivitis, episcleritis, scleritis, corneal ulceration, uveitis, retinal vasculitis, optic neuropathy, orbital mass, orbital cellulitis, and obstruction of the nasolacrimal duct. The multiple ophthalmic and systemic complications in these 40 patients and the importance of establishing the pathologic diagnosis are discussed. Treatment with corticosteroids and immunosuppressive agents has dramatically improved the prognosis, although substantial mortality (four patients died of Wegener's granulomatosis) and ocular morbidity (three eyes were enucleated) are still associated with this disease.