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Eosinophilic vasculitis with atypical features
Allergy
grand rounds
Eosinophilic vasculitis with atypical features Michael J. Chandler, M.D., Leslie C. Grammer, Roy Patterson, M.D. Chicago, Ill.
Dr. Grammer: The systemic necrotizing vasculitides are a group of uncommon diseases of undetermined causes that have been classified into categories or syndrom’es based on clinical features, pathologic findings, and prognosis. In many patients with vasculitis, the pattern of disease defies ready classification. This is especially true of patients with vasculitis and eosinophilia. The differential diagnosis of these disorders can be quite extensive, and a given patient may have f;:atures pathognomonic of several d&orders. The prognosis of some may be grave, whereas others are self-limited. We present a patient with systemic necrotizing vasculitis and eosinophilia who demonstrated clinical features atypical of the well-described vasculitis syndromes. Psychosocial factors hindered the establishment of the correct diagnosis and seriously complicated the management of the patient. We will review the differential diagnosis of vasculitis and describe a therapeutic strategy designed to treat an unreliable and noncompliant patient with a life-threatening disease. CASE PRESENTATION
Dr. Chandler: A 35-year-old black man was admitted to the Oral Surgery Service of the Veterans Administration Lakeside Medical Center for treatment of a traumatic fracture of the mandible. Routine preoperative complete blood count revealed a total leukocyte count of 22,000/mm3 with 54% eosinophils. After surgery the patient was transferred to the Medical Service for evaluation of eosinophilia. The patient described dyspnea on exertion, night
From the Section of Allergy-Immunology, Department of Medicine, Northwestern University Medical School, Chicago, 111. Supported by United States Public Health Service Grant AI 11403 and the Ernest S. Bazley grant. Received for publication May 13, 1985. Accepted for publication Oct. 16, 1985. Reprint requests: Roy Patterson, M.D., 303 E. Chicago Ave., Chicago, IL 6061 I.
M.D., and
sweats, myalgias, knee pain, and an f£ weight loss during the previous 3 months. He said he had used intravenous cocaine during the previous 10 years, but opiates were also found in his urine on admission. He told of alcohol abuse and of smoking one pack of cigarettes a day for 10 years. He was heterosexual and denied recent hepatitis. There was no history of asthma nor were there any known allergies. Physical examination at this time revealed a thin black man in no acute distress. Blood pressure was 108/60, pulse was 108, and respiration was 16. Temperature was 98”. Examination of the head and neck disclosed wires in the mandibular region, a left posterior cervical lymph node, and shotty anterior cervical adenopathy. Ophthalmoscopic examination was recorded as unremarkable. His chest was clear to auscultation and percussion. The heart tones were normal, and the peripheral pulses were full and equal. There was no cyanosis or clubbing of the digits nor was there peripheral edema. The abdomen was of normal contour. The liver span was estimated at 10 cm in the midclavicular line. A spleen tip was not felt. The rectal examination was normal, and tests for occult blood in the stool were negative. Neurologitally, the patient was found to have no deficits. The complete blood count was repeated, and the total leukocyte count was 22,70O/mm’ with 68% eosinophils, 16% polymorphs, 2% bands, 11% lymphocytes, and 3% monocytes. The hemoglobin was 10.2 gm/dl, and the hematocrit was 32%. The erythrocyte sedimentation rate was 137 mm/hr Westergren. Coagulation studies were normal. A sickle cell screen was normal. His blood chemistries were normal except for an elevated total protein of 8.3 gm/dl, and a lactic dehydrogenase of 254 units. The blood urea nitrogen was 14 mg/dl, and the serum creatinine was 0.9 mg/dl. The electrocardiogram fulfilled voltage cri741
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teria for left ventricular hypertrophy with a sinus rhythm. Urinalysis was normal. Chest x-ray film demonstrated apical bullous changes with bibasilar infiltrates absent on films taken 2 years before. Arterial blood gases were pH, 7.44; PcoZ, 44; and PO,, 83 while room air was breathed. The patient was believed to have a systemic disorder with an eosinophilic component. No organisms grew in three bacterial blood cultures. Three specimens of stool contained no ova or parasites. A bone marrow aspirate was interpreted as normal with increased eosinophils. Bacterial, fungal, and mycobacterial cultures of the bone marrow aspirate were sterile. Two sputum samples were stain and culture negative for mycobacteria. A 5 unit purified protein derivative was negative at 48 hours with a positive reaction to mumps antigen. A rheumatoid factor was positive in a 1: 80 titer. An antinuclear antibody test was negative. Cold agglutinins were present in a 1: 64 titer. A hepatitis B surface antigen was present. The Veneral Disease Research Laboratory test was positive in two dilutions, but the fluorescent treponemal antibody was negative. CH,, was 50 units, C3, 127 (80 to 140); and C4, 26 (20 to 60). Immunoglobulins were as follows: IgG, 2483 mg/dl (800 to 1800); IgA, 254 mg/dl (90 to 145); IgM, 1361 mg/dl (60 to 250); and IgE, 8500 rig/ml (50 to 1000). Pulmonary function tests were performed. The FEV, was 83% of predicted; FVC, 75% of predicted; and the flow volume loop, functional residual capacity, total lung capacity, and diffusing capacity were all normal. An M-mode and two-dimensional echocardiogram documented concentric left ventricular hypertrophy, but no valvular or endocardial lesions were observed. The patient was seen by the Allergy-Immunology Service of Northwestern Memorial Hospital 3 weeks after admission. No allergic problem was identified by history or skin tests to a panel of common inhalant allergens. There were no signs of asthma. Allergic bronchopulmonary aspergillosis was excluded by a negative intradermal test with Aspergillus antigen. Systemic vasculitis was suspected, and a skin, muscle, and nerve biopsy was performed. Although samples of skin, muscle, and nerve were sampled, only skin and fibrovascular tissue was observed histologically. The skin revealed no vasculitis. Immunofluorescence of the skin biopsy specimen demonstrated weak nonspecific binding of complement, fibrinogen, IgE, and IgM. The fibrovascular tissue contained small muscular arteries with necrosis as well as eosinophilic and plasma cell infiltration in
J. ALLERGY CLIN. IMMUNOL. MAY 1986
all layers of the vessel wall. No involvement of vessels of other types or size was noted. No foreign material was found. The serious, life-threatening nature of this disease was explained to the patient who was started on a course of prednisone, 60 mglday. Shortly after starting the prednisone, the patient left the hospital on a 48-hour pass. When he returned, he gave a history of anginal-type chest pain. Electrocardiogram demonstrated ischemic ST-T wave changes. Cardiac isoenzymes were negative, and repeat echocardiogram demonstrated no discrete wall-motion abnormalities. There were no recurrent episodes of chest pain, but the cardiogram remained abnormal. A thallium stress test was recommended to follow-up possible coronary artery disease. After 1 week of daily prednisone of 60 mg/day, the patient reported improved exercise tolerance, diminished arthralgias, and slight improvement of distal extremity paresthesias. The sedimentation rate declined to 47 mm/hr, and the infiltrates on chest x-ray film and the eosinophilia disappeared. The patient was discharged with weekly follow-up visits in the Al1ergylImmunology Clinic of Northwestern. Our initial therapeutic goal was to continue highdose daily steroids until the eosinophil count and sedimentation rate normalized and there was amelioration of the systemic symptoms. At that point we intended to try to convert the patient to an alternate day regimen of prednisone. The patient failed to keep two clinic appointments as well as the appointment for the stress test. He did appear in the clinic 3 weeks after discharge complaining of anorexia, 2-pound weight loss, knee arthralgias, myalgias, and cold-induced acrocyanosis of the fingers. His sedimentation rate was 47 mm/hr. Ophthalmoscopic examination revealed retinal pigmentary disruption. The muscle biopsy site on his leg had not healed. Noncompliance with medical management was obvious. The serious, life-threatening nature of his disease was again explained to the patient who promised to follow our medical advice faithfully. The patient was instructed to take 60 mg of prednisone daily and return in 1 week. The patient next appeared 2 weeks later. He had run out of prednisone shortly after his last visit, resulting in worsened systemic symptoms, acrocyanosis, and pedal edema. Ophthalmoscopic examination revealed arteriovenous nicking with segmentation of some retinal veins along with the pigmentary disruption already described. No hemorrhages or exudates were observed. Noncompliance with medical care was obvious, and the patient was administered an injection of depot
VOLUME 77 NUMBER 5
methylprednisolone, 360 mg, intramuscularly. Five days later the patient, who had allegedly stolen a computer, was brought to the emergency room at Northwestern Memorial Hospital by the Chicago police for medical evaluation before imprisonment. His sedimentation rate was 25 mm/hr, and his leukocyte count was 11,700/mm3 with 0% eosinophils. His dyspnea and arthralgias had improved. Depot methylprednisolone, 400 mg, was administered. Two weeks later he reported sustained improvement of his dyspnea and arthralgias but still has significant cold-induced acrocyanosis. There were no new retinal changes. Depot methylprednisolone, 300 mg intramuscularly, was administered. The patient was observed 3 weeks later in the Veterans Administration Lakeside Medical Center where he was admitted to have his mandibular wires removed. He complained of dyspnea on exertion, intermittent arthralgias, and cold-induced blanching of the digits without cyanosis. His sedimentation rate was 44 mmihr, and his total leukocyte count was 78OO/mm’ with no eosinophils. The chest x-ray film was clear, but the cardiogram was persistently abnormal. In preparation for surgery, hydrocortisone, 40 mg, intramuscularly, twice daily, was administered for 5 days. By this time the sedimentation rate had fallen to 22 mm/hr. Arterial flow studies in upper and lower extremities were normal. Blood was collected for cryoglobulin determination, which was positive. Quantitative immunoglobulins were repeated. Immunoglobulins were as follows: IgG, 1014 mg/dl; IgA, 141 mg/dl; IgM, 627 mg/dl; and IgE, 1325 rig/ml. Assay of the cryoglobulin demonstrated that it contained monoclonal IgM kappa, 1.1 mg/dl, and polyclonal IgG, 0.07 mg/ dl. Opthalmologic evaluation and fluorescein angiography disclosed talc deposition in the retina, presumably related to intravenous drug abuse. ’ He was discharged after receiving depot methylprednisolone, 400 mg, intramuscularly. He was observed I month later, symptomatic again with a sedimentation rate of 72 mm/hr. Depot methylprednisolone, 400 mg intramuscularly, was administered again, and the sedimentation rate 2 weeks later was 40 mm/hr. The patient continues to appear erratically in our clinics. The injections of depot methylprednisolone provide symptomatic relief for approximately 2 weeks. The patient continues to inject intravenous cocaine. Discussion with the patient about the seriousness of his problems along with offers of free medical care has not resulted in adherence to a conventional medical regimen. We concluded that the use of
Eosinophilic
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atypical
features
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depot methylprednisolone was demonstrably effective, although it is not an ideal method to treat systemic vasculitis. DISCUSSION
Dr. Patterson: The patient described above had a multisystem disorder characterized by constitutional symptoms of weight loss and malaise accompanied by arthalgias, myalgias, dyspnea, and cold-induced acrocyanosis. Diagnosis should be made as rapidly as possible in these cases because vasculitis may progress rapidly. A histologic diagnosis could have been made more rapidly in this case. If the skin and muscle biopsy specimens had been negative, a lung biopsy would have been done. A tissue diagnosis is of major value in the subsequent management. Prednisone administered empirically without a tissue diagnosis would have resulted in improvement in clinical and laboratory abnormalities; however, the long-term medical management of this patient with his psychosocial deprivation would have been difficult or impossible without a tissue diagnosis. Eosinophilia was prominent. Biopsy material revealed a necrotizing eosinophilic vasculitis without granulomata. Classification of the various vasculitic disorders has been difficult, in part, because of the considerable overlap often observed in the clinical and laboratory features of these diseases. Fauci has proposed a classification scheme for the various vasculitides including the PAN group of systemic necrotizing vasculitis, which has caused the most difficulty in categorization according to Fauci . ‘-4 Dr. Chandler: Classic PAN is a necrotizing vasculitis of small and medium sized muscular arteries. There is infiltration of the vessel wall by polymorphonuclear leukocytes followed by mononuclear cell infiltration in all layers of the vessel wall. Intimal proliferation, vessel-wall degeneration, fibrinoid necrosis, and thrombosis with end organ ischemia are observed in varying degrees. Visceral and renal involvement along with mononeuritis multiplex is common. The lung is not characteristically involved. Allergic histories, eosinophilia, and eosinophilic tissue infiltrates are unusual.’ A second category of this group of necrotizing vasculitis is the syndrome of allergic angiitis and granulomatosis often called the Churg-Strauss syndrome.‘-’ This is a rare disease whose incidence is unknown. It is characterized by granulomatous vasculitis of multiple organ systems, although lesions identical to classic polyarteritis can be observed. This disease is unique for the frequency of involvement of pulmonary vessels, the presence of intra and extravascular gran-
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uloma formation, vasculitis of blood vessels of various sizes, and eosinophilic tissue infiltration in association with severe asthma and peripheral eosinophilia.3 This patient had the pulmonary infiltrates, eosinophilia, cardiac disease, and small vessel involvement characteristic of allergic angiitis without the allergic diathesis, granulomata, or asthma. He also had the hepatitis B surface antigenemia and monoclonal IgM cryoglobulin without the hypertension or renal disease that is more characteristic of classic polyarteritis
J. ALLERGY CLIN. IMMUNOL. MAY 1996
et al.
2-4, 6, 7
This patient falls into the category of a group of systemic necrotizing vasculitides, the ‘ ‘polyangiitis overlap syndrome.” There are patients who manifest clinical and pathologic characteristics of both classic PAN and allergic angiitis/granulomatosis and thus do not fit exactly into either of the first two categories. This form of systemic necrotizing vasculitis is more common than either classic PAN or Churg-Strauss syndrome.4 It has multisystem involvement with associated clinical manifestations. Lesions of arterioles, venules, and muscular arteries may be present. The recognition of this “overlap syndrome” underscores the fact that there is a continuum of disease between PAN and Churg-Strauss syndrome. Despite the difficulty in distinguishing among these disorders, it is critical to recognize that they are equally likely to cause devastating and life-threatening clinical manifestations. Thus, as emphasized earlier, appropriate diagnostic and therapeutic intervention must not be delayed.4. 5 Dr. Grammer: The differential diagnosis of eosinophilia of the magnitude observed in this patient (> 10,000 eosinophils per cubic millimeter) consists of eosinophilic leukemia, hypereosinophilic syndrome, parasitic diseases, eosinophilic pneumonia, drug reactions, and systemic necrotizing vasculitis of the Churg-Strauss syndrome or polyangiitis overlap type.‘, 9 Considering the patient’s history and multisystem organ involvement, the most likely diagnoses were eosinophilic leukemia, hypereosinophilic syndrome, systemic necrotizing vasculitis, and mainline pulmonary granulomatosis.” Whenever systemic necrotizing vasculitis is a major diagnostic consideration, it is imperative that a tissue diagnosis be obtained as quickly as possible so that appropriate, lifesaving therapy can be instituted. The biopsy site that is chosen should be the involved site that would cause the least morbidity. For instance, in this patient we chose a skin and muscle biopsy site rather than an open lung biopsy site. The prognosis of untreated PAN or Churg-Strauss syndrome is very poor with 5-year survival rates of
about 10% being reported.3 Death in PAN usually results from renal failure or cardiovascular- or gastrointestinal-related causes, whereas death in ChurgStrauss syndrome is usually from cardiovascular or pulmonary causes.4, ” The appropriate use of corticosteroids has been reported to have improved the 5year survival to about 50% in PAN and Churg-Strauss syndrome. Although corticosteroids can clearly induce remissions in some cases of PAN and ChurgStrauss syndrome, they may also induce only partial remission, so that insidious, relentless organ damage may still occur. The use of cytotoxic agents has resulted in major advantages in the treatment of some cases of systemic necrotizing vasculitis. In general, the 5-year survival has increased from about 50% with corticosteroids alone to 80% with corticosteroids and immunosuppressive agents.3 Our patient responded to corticosteroids alone and has been maintained on corticosteroids without cytotoxic agents. The typical corticosteroid regimens that are useful in systemic necrotizing vasculitis begin with daily corticosteroids like prednisone in the range of 1 mg/ kg/day.3 Once the disease has gone into remission, the steroid dose is tapered and converted to an alternate day regimen, if it is possible. Alternate day steroid regimens provide the requisite anti-inflammatory effects while undesirable side effects are minimized. The steroids are slowly tapered and eventually stopped, provided that the remission is maintained. In this drug addict, who was eventually convicted and put on probation for stealing a computer, the usual prednisone regimen was unsuccessful because of the patient’s inability to comply with it. We have reported schizophrenic patients with asthma with similar compliance problems in whom depot methylprednisolone has been essential.12 We have also used a depot methylprednisolone regimen for this noncompliant patient. Although this is a suboptimal therapy, it has resulted in the best control obtainable in this patient. Because of the inability of this patient to comply with reasonable medical management, we cannot risk the use of cytotoxic agents. REFERENCES I. Atlee WE: Talc and cornstarch emboli in eyes of drug abusers. JAMA 219:49, 1972 2. Fauci AS, Haynes BF, Katz P: The spectrum of vasculitis. Ann Intern Med 89560, 1978 3. Cupps TR, Fauci AS: The vasculitides. Philadelphia, 1981, WB Saunders Co, pp 26-49 4. Fauci AS: Vasculitis. J ALLERGY CLIN IMMUNOL 72:211, 1983 5. Churg J, Strauss L: Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Path01 27:277, 1951 6. Lanham JG, Elkon KB, Pusey CD, Hughes GR: Systemic
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vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine 63:65, 1984 7. Bruet J-C, Clauvel J-P, Danon F, Klein M, Seligmann M: Biological and clinical significance of cryglobulins. Am J Med 57775, 1974 8. Patterson R, Irons JS, Kelly JF, Mattson JR, Oh SH: Pulmonary infiltrates with eosinophilia. J ALLERGY CLIN IMMUNOI. 53:245, 1973 9. Schatz M. Wasserman S, Patterson R: Eosinophils and immunologic lung disease. Med Clin North Am 65:1055, 1981
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10. Pare JAP, Fraser RG, Hogg JC, Howlett JG, Murphy SB: Pulmonary “mainline” granulomatosis: tdlcosis of intravenous methadone abuse. Medicine 58229, 1979 11. Chumbley LC, Harrison EC Jr, DeRemee RA: Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Mayo Clin Proc 521477, 1977 12. Sonin L, Patterson R: Corticosteroid-dependent asthma and schizophrenia. Arch Intern Med 144554, 1984
Prevalence of house dust mites in nursing homes in southwest Ohio 13. L. Vyszenski-Moher, M.Sc., L. G. Arlian, Ph.D., I. L. Bernstein, .J. S. Gallagher, Ph.D. Dayton and Cincinnati, Ohio
M.D., and
1)etmatophagoides spp house dust mites were found to be prevalent in geriatric nursing homes in southwestern Ohio. Mite density was lower in nursing homes than in private homes in comparable dust-sampling areas and at similar times of the year. Generally, fewer mattresses, floors, and articles ofjiirniture were mite positive in nursing homes by comparison to private homes. Lower institutional mite levels were attributed to frequent linen and mattress cover changes and rigorous cleaning practices, coupled with the lack of a favorable mite environment provided by high ambient temperatures, low relative humidity, tiled or vinyl-covered floors and furniture, and covered or encased mattresses. (J ALLERGY CLIN IMMUNOL 77:745-a, 1986.)
The house dust mites, Dermatophagoides farinae and D. ptermyssinus, have been established as the sources of major allergens for patients sensitive to house dust. These mites are most prevalent in homes in more humid geographic areas where mite density may range from a few to >18,OOO/gm of dust in specific locations within the home.’ Within the home mites are more prevalent in carpeted floor areas, fabric-upholstered furniture, and mattresses that are used most frequently, and they are rare or absent in other areas. Although this distribution and dependence on
From the Departments of Biological Sciences and Physiology, College of Science and Engineering and School of Medicine, Wright State University, Dayton, Ohio, and Department of Medicine, Division of Immunology, University of Cincinnati Medical Center, Cincinnati, Ohio. Supported by Grant ROI AI I3702 from the National Institute of Allergy and Infectious Diseases. Received for publication Sept. 24, 1985. Accepted for publication Nov. 20, 1985. Reprint requests: ;L. G. Arlian, Department of Biological Sciences and Physiology and Biophysics, Wright State University, Dayton, OH 45435.
I
I Abbreviation RH:
I
Relative
used humidity I
humans is not clearly understood, when sufficiently high RH exists in the mite microhabitat, presumably, accumulating skin scales that are shed during constant or frequent use of these areas or furniture serve as food to support mite-population development. In homes where RH is not continually or sufficiently high to support mite populations, human use of beds and furniture may provide sufficient moisture to these microhabitats to support significant mite levels, and these locations may become the major foci in the home. ’ Because of these ecologic relationships and the large amount of time institutionalized patients are confined to beds and other furniture, they could potentially provide enough dander and moisture to support large mite populations in these settings. In hospitals, despite the fact that patients are confined primarily to beds, mite prevalence is generally Iow,~-’ probably because of the high hygienic standards, plastic mat745
grand rounds
Eosinophilic vasculitis with atypical features Michael J. Chandler, M.D., Leslie C. Grammer, Roy Patterson, M.D. Chicago, Ill.
Dr. Grammer: The systemic necrotizing vasculitides are a group of uncommon diseases of undetermined causes that have been classified into categories or syndrom’es based on clinical features, pathologic findings, and prognosis. In many patients with vasculitis, the pattern of disease defies ready classification. This is especially true of patients with vasculitis and eosinophilia. The differential diagnosis of these disorders can be quite extensive, and a given patient may have f;:atures pathognomonic of several d&orders. The prognosis of some may be grave, whereas others are self-limited. We present a patient with systemic necrotizing vasculitis and eosinophilia who demonstrated clinical features atypical of the well-described vasculitis syndromes. Psychosocial factors hindered the establishment of the correct diagnosis and seriously complicated the management of the patient. We will review the differential diagnosis of vasculitis and describe a therapeutic strategy designed to treat an unreliable and noncompliant patient with a life-threatening disease. CASE PRESENTATION
Dr. Chandler: A 35-year-old black man was admitted to the Oral Surgery Service of the Veterans Administration Lakeside Medical Center for treatment of a traumatic fracture of the mandible. Routine preoperative complete blood count revealed a total leukocyte count of 22,000/mm3 with 54% eosinophils. After surgery the patient was transferred to the Medical Service for evaluation of eosinophilia. The patient described dyspnea on exertion, night
From the Section of Allergy-Immunology, Department of Medicine, Northwestern University Medical School, Chicago, 111. Supported by United States Public Health Service Grant AI 11403 and the Ernest S. Bazley grant. Received for publication May 13, 1985. Accepted for publication Oct. 16, 1985. Reprint requests: Roy Patterson, M.D., 303 E. Chicago Ave., Chicago, IL 6061 I.
M.D., and
sweats, myalgias, knee pain, and an f£ weight loss during the previous 3 months. He said he had used intravenous cocaine during the previous 10 years, but opiates were also found in his urine on admission. He told of alcohol abuse and of smoking one pack of cigarettes a day for 10 years. He was heterosexual and denied recent hepatitis. There was no history of asthma nor were there any known allergies. Physical examination at this time revealed a thin black man in no acute distress. Blood pressure was 108/60, pulse was 108, and respiration was 16. Temperature was 98”. Examination of the head and neck disclosed wires in the mandibular region, a left posterior cervical lymph node, and shotty anterior cervical adenopathy. Ophthalmoscopic examination was recorded as unremarkable. His chest was clear to auscultation and percussion. The heart tones were normal, and the peripheral pulses were full and equal. There was no cyanosis or clubbing of the digits nor was there peripheral edema. The abdomen was of normal contour. The liver span was estimated at 10 cm in the midclavicular line. A spleen tip was not felt. The rectal examination was normal, and tests for occult blood in the stool were negative. Neurologitally, the patient was found to have no deficits. The complete blood count was repeated, and the total leukocyte count was 22,70O/mm’ with 68% eosinophils, 16% polymorphs, 2% bands, 11% lymphocytes, and 3% monocytes. The hemoglobin was 10.2 gm/dl, and the hematocrit was 32%. The erythrocyte sedimentation rate was 137 mm/hr Westergren. Coagulation studies were normal. A sickle cell screen was normal. His blood chemistries were normal except for an elevated total protein of 8.3 gm/dl, and a lactic dehydrogenase of 254 units. The blood urea nitrogen was 14 mg/dl, and the serum creatinine was 0.9 mg/dl. The electrocardiogram fulfilled voltage cri741
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et al.
teria for left ventricular hypertrophy with a sinus rhythm. Urinalysis was normal. Chest x-ray film demonstrated apical bullous changes with bibasilar infiltrates absent on films taken 2 years before. Arterial blood gases were pH, 7.44; PcoZ, 44; and PO,, 83 while room air was breathed. The patient was believed to have a systemic disorder with an eosinophilic component. No organisms grew in three bacterial blood cultures. Three specimens of stool contained no ova or parasites. A bone marrow aspirate was interpreted as normal with increased eosinophils. Bacterial, fungal, and mycobacterial cultures of the bone marrow aspirate were sterile. Two sputum samples were stain and culture negative for mycobacteria. A 5 unit purified protein derivative was negative at 48 hours with a positive reaction to mumps antigen. A rheumatoid factor was positive in a 1: 80 titer. An antinuclear antibody test was negative. Cold agglutinins were present in a 1: 64 titer. A hepatitis B surface antigen was present. The Veneral Disease Research Laboratory test was positive in two dilutions, but the fluorescent treponemal antibody was negative. CH,, was 50 units, C3, 127 (80 to 140); and C4, 26 (20 to 60). Immunoglobulins were as follows: IgG, 2483 mg/dl (800 to 1800); IgA, 254 mg/dl (90 to 145); IgM, 1361 mg/dl (60 to 250); and IgE, 8500 rig/ml (50 to 1000). Pulmonary function tests were performed. The FEV, was 83% of predicted; FVC, 75% of predicted; and the flow volume loop, functional residual capacity, total lung capacity, and diffusing capacity were all normal. An M-mode and two-dimensional echocardiogram documented concentric left ventricular hypertrophy, but no valvular or endocardial lesions were observed. The patient was seen by the Allergy-Immunology Service of Northwestern Memorial Hospital 3 weeks after admission. No allergic problem was identified by history or skin tests to a panel of common inhalant allergens. There were no signs of asthma. Allergic bronchopulmonary aspergillosis was excluded by a negative intradermal test with Aspergillus antigen. Systemic vasculitis was suspected, and a skin, muscle, and nerve biopsy was performed. Although samples of skin, muscle, and nerve were sampled, only skin and fibrovascular tissue was observed histologically. The skin revealed no vasculitis. Immunofluorescence of the skin biopsy specimen demonstrated weak nonspecific binding of complement, fibrinogen, IgE, and IgM. The fibrovascular tissue contained small muscular arteries with necrosis as well as eosinophilic and plasma cell infiltration in
J. ALLERGY CLIN. IMMUNOL. MAY 1986
all layers of the vessel wall. No involvement of vessels of other types or size was noted. No foreign material was found. The serious, life-threatening nature of this disease was explained to the patient who was started on a course of prednisone, 60 mglday. Shortly after starting the prednisone, the patient left the hospital on a 48-hour pass. When he returned, he gave a history of anginal-type chest pain. Electrocardiogram demonstrated ischemic ST-T wave changes. Cardiac isoenzymes were negative, and repeat echocardiogram demonstrated no discrete wall-motion abnormalities. There were no recurrent episodes of chest pain, but the cardiogram remained abnormal. A thallium stress test was recommended to follow-up possible coronary artery disease. After 1 week of daily prednisone of 60 mg/day, the patient reported improved exercise tolerance, diminished arthralgias, and slight improvement of distal extremity paresthesias. The sedimentation rate declined to 47 mm/hr, and the infiltrates on chest x-ray film and the eosinophilia disappeared. The patient was discharged with weekly follow-up visits in the Al1ergylImmunology Clinic of Northwestern. Our initial therapeutic goal was to continue highdose daily steroids until the eosinophil count and sedimentation rate normalized and there was amelioration of the systemic symptoms. At that point we intended to try to convert the patient to an alternate day regimen of prednisone. The patient failed to keep two clinic appointments as well as the appointment for the stress test. He did appear in the clinic 3 weeks after discharge complaining of anorexia, 2-pound weight loss, knee arthralgias, myalgias, and cold-induced acrocyanosis of the fingers. His sedimentation rate was 47 mm/hr. Ophthalmoscopic examination revealed retinal pigmentary disruption. The muscle biopsy site on his leg had not healed. Noncompliance with medical management was obvious. The serious, life-threatening nature of his disease was again explained to the patient who promised to follow our medical advice faithfully. The patient was instructed to take 60 mg of prednisone daily and return in 1 week. The patient next appeared 2 weeks later. He had run out of prednisone shortly after his last visit, resulting in worsened systemic symptoms, acrocyanosis, and pedal edema. Ophthalmoscopic examination revealed arteriovenous nicking with segmentation of some retinal veins along with the pigmentary disruption already described. No hemorrhages or exudates were observed. Noncompliance with medical care was obvious, and the patient was administered an injection of depot
VOLUME 77 NUMBER 5
methylprednisolone, 360 mg, intramuscularly. Five days later the patient, who had allegedly stolen a computer, was brought to the emergency room at Northwestern Memorial Hospital by the Chicago police for medical evaluation before imprisonment. His sedimentation rate was 25 mm/hr, and his leukocyte count was 11,700/mm3 with 0% eosinophils. His dyspnea and arthralgias had improved. Depot methylprednisolone, 400 mg, was administered. Two weeks later he reported sustained improvement of his dyspnea and arthralgias but still has significant cold-induced acrocyanosis. There were no new retinal changes. Depot methylprednisolone, 300 mg intramuscularly, was administered. The patient was observed 3 weeks later in the Veterans Administration Lakeside Medical Center where he was admitted to have his mandibular wires removed. He complained of dyspnea on exertion, intermittent arthralgias, and cold-induced blanching of the digits without cyanosis. His sedimentation rate was 44 mmihr, and his total leukocyte count was 78OO/mm’ with no eosinophils. The chest x-ray film was clear, but the cardiogram was persistently abnormal. In preparation for surgery, hydrocortisone, 40 mg, intramuscularly, twice daily, was administered for 5 days. By this time the sedimentation rate had fallen to 22 mm/hr. Arterial flow studies in upper and lower extremities were normal. Blood was collected for cryoglobulin determination, which was positive. Quantitative immunoglobulins were repeated. Immunoglobulins were as follows: IgG, 1014 mg/dl; IgA, 141 mg/dl; IgM, 627 mg/dl; and IgE, 1325 rig/ml. Assay of the cryoglobulin demonstrated that it contained monoclonal IgM kappa, 1.1 mg/dl, and polyclonal IgG, 0.07 mg/ dl. Opthalmologic evaluation and fluorescein angiography disclosed talc deposition in the retina, presumably related to intravenous drug abuse. ’ He was discharged after receiving depot methylprednisolone, 400 mg, intramuscularly. He was observed I month later, symptomatic again with a sedimentation rate of 72 mm/hr. Depot methylprednisolone, 400 mg intramuscularly, was administered again, and the sedimentation rate 2 weeks later was 40 mm/hr. The patient continues to appear erratically in our clinics. The injections of depot methylprednisolone provide symptomatic relief for approximately 2 weeks. The patient continues to inject intravenous cocaine. Discussion with the patient about the seriousness of his problems along with offers of free medical care has not resulted in adherence to a conventional medical regimen. We concluded that the use of
Eosinophilic
vasculitis
with
atypical
features
743
depot methylprednisolone was demonstrably effective, although it is not an ideal method to treat systemic vasculitis. DISCUSSION
Dr. Patterson: The patient described above had a multisystem disorder characterized by constitutional symptoms of weight loss and malaise accompanied by arthalgias, myalgias, dyspnea, and cold-induced acrocyanosis. Diagnosis should be made as rapidly as possible in these cases because vasculitis may progress rapidly. A histologic diagnosis could have been made more rapidly in this case. If the skin and muscle biopsy specimens had been negative, a lung biopsy would have been done. A tissue diagnosis is of major value in the subsequent management. Prednisone administered empirically without a tissue diagnosis would have resulted in improvement in clinical and laboratory abnormalities; however, the long-term medical management of this patient with his psychosocial deprivation would have been difficult or impossible without a tissue diagnosis. Eosinophilia was prominent. Biopsy material revealed a necrotizing eosinophilic vasculitis without granulomata. Classification of the various vasculitic disorders has been difficult, in part, because of the considerable overlap often observed in the clinical and laboratory features of these diseases. Fauci has proposed a classification scheme for the various vasculitides including the PAN group of systemic necrotizing vasculitis, which has caused the most difficulty in categorization according to Fauci . ‘-4 Dr. Chandler: Classic PAN is a necrotizing vasculitis of small and medium sized muscular arteries. There is infiltration of the vessel wall by polymorphonuclear leukocytes followed by mononuclear cell infiltration in all layers of the vessel wall. Intimal proliferation, vessel-wall degeneration, fibrinoid necrosis, and thrombosis with end organ ischemia are observed in varying degrees. Visceral and renal involvement along with mononeuritis multiplex is common. The lung is not characteristically involved. Allergic histories, eosinophilia, and eosinophilic tissue infiltrates are unusual.’ A second category of this group of necrotizing vasculitis is the syndrome of allergic angiitis and granulomatosis often called the Churg-Strauss syndrome.‘-’ This is a rare disease whose incidence is unknown. It is characterized by granulomatous vasculitis of multiple organ systems, although lesions identical to classic polyarteritis can be observed. This disease is unique for the frequency of involvement of pulmonary vessels, the presence of intra and extravascular gran-
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uloma formation, vasculitis of blood vessels of various sizes, and eosinophilic tissue infiltration in association with severe asthma and peripheral eosinophilia.3 This patient had the pulmonary infiltrates, eosinophilia, cardiac disease, and small vessel involvement characteristic of allergic angiitis without the allergic diathesis, granulomata, or asthma. He also had the hepatitis B surface antigenemia and monoclonal IgM cryoglobulin without the hypertension or renal disease that is more characteristic of classic polyarteritis
J. ALLERGY CLIN. IMMUNOL. MAY 1996
et al.
2-4, 6, 7
This patient falls into the category of a group of systemic necrotizing vasculitides, the ‘ ‘polyangiitis overlap syndrome.” There are patients who manifest clinical and pathologic characteristics of both classic PAN and allergic angiitis/granulomatosis and thus do not fit exactly into either of the first two categories. This form of systemic necrotizing vasculitis is more common than either classic PAN or Churg-Strauss syndrome.4 It has multisystem involvement with associated clinical manifestations. Lesions of arterioles, venules, and muscular arteries may be present. The recognition of this “overlap syndrome” underscores the fact that there is a continuum of disease between PAN and Churg-Strauss syndrome. Despite the difficulty in distinguishing among these disorders, it is critical to recognize that they are equally likely to cause devastating and life-threatening clinical manifestations. Thus, as emphasized earlier, appropriate diagnostic and therapeutic intervention must not be delayed.4. 5 Dr. Grammer: The differential diagnosis of eosinophilia of the magnitude observed in this patient (> 10,000 eosinophils per cubic millimeter) consists of eosinophilic leukemia, hypereosinophilic syndrome, parasitic diseases, eosinophilic pneumonia, drug reactions, and systemic necrotizing vasculitis of the Churg-Strauss syndrome or polyangiitis overlap type.‘, 9 Considering the patient’s history and multisystem organ involvement, the most likely diagnoses were eosinophilic leukemia, hypereosinophilic syndrome, systemic necrotizing vasculitis, and mainline pulmonary granulomatosis.” Whenever systemic necrotizing vasculitis is a major diagnostic consideration, it is imperative that a tissue diagnosis be obtained as quickly as possible so that appropriate, lifesaving therapy can be instituted. The biopsy site that is chosen should be the involved site that would cause the least morbidity. For instance, in this patient we chose a skin and muscle biopsy site rather than an open lung biopsy site. The prognosis of untreated PAN or Churg-Strauss syndrome is very poor with 5-year survival rates of
about 10% being reported.3 Death in PAN usually results from renal failure or cardiovascular- or gastrointestinal-related causes, whereas death in ChurgStrauss syndrome is usually from cardiovascular or pulmonary causes.4, ” The appropriate use of corticosteroids has been reported to have improved the 5year survival to about 50% in PAN and Churg-Strauss syndrome. Although corticosteroids can clearly induce remissions in some cases of PAN and ChurgStrauss syndrome, they may also induce only partial remission, so that insidious, relentless organ damage may still occur. The use of cytotoxic agents has resulted in major advantages in the treatment of some cases of systemic necrotizing vasculitis. In general, the 5-year survival has increased from about 50% with corticosteroids alone to 80% with corticosteroids and immunosuppressive agents.3 Our patient responded to corticosteroids alone and has been maintained on corticosteroids without cytotoxic agents. The typical corticosteroid regimens that are useful in systemic necrotizing vasculitis begin with daily corticosteroids like prednisone in the range of 1 mg/ kg/day.3 Once the disease has gone into remission, the steroid dose is tapered and converted to an alternate day regimen, if it is possible. Alternate day steroid regimens provide the requisite anti-inflammatory effects while undesirable side effects are minimized. The steroids are slowly tapered and eventually stopped, provided that the remission is maintained. In this drug addict, who was eventually convicted and put on probation for stealing a computer, the usual prednisone regimen was unsuccessful because of the patient’s inability to comply with it. We have reported schizophrenic patients with asthma with similar compliance problems in whom depot methylprednisolone has been essential.12 We have also used a depot methylprednisolone regimen for this noncompliant patient. Although this is a suboptimal therapy, it has resulted in the best control obtainable in this patient. Because of the inability of this patient to comply with reasonable medical management, we cannot risk the use of cytotoxic agents. REFERENCES I. Atlee WE: Talc and cornstarch emboli in eyes of drug abusers. JAMA 219:49, 1972 2. Fauci AS, Haynes BF, Katz P: The spectrum of vasculitis. Ann Intern Med 89560, 1978 3. Cupps TR, Fauci AS: The vasculitides. Philadelphia, 1981, WB Saunders Co, pp 26-49 4. Fauci AS: Vasculitis. J ALLERGY CLIN IMMUNOL 72:211, 1983 5. Churg J, Strauss L: Allergic granulomatosis, allergic angiitis, and periarteritis nodosa. Am J Path01 27:277, 1951 6. Lanham JG, Elkon KB, Pusey CD, Hughes GR: Systemic
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vasculitis with asthma and eosinophilia: a clinical approach to the Churg-Strauss syndrome. Medicine 63:65, 1984 7. Bruet J-C, Clauvel J-P, Danon F, Klein M, Seligmann M: Biological and clinical significance of cryglobulins. Am J Med 57775, 1974 8. Patterson R, Irons JS, Kelly JF, Mattson JR, Oh SH: Pulmonary infiltrates with eosinophilia. J ALLERGY CLIN IMMUNOI. 53:245, 1973 9. Schatz M. Wasserman S, Patterson R: Eosinophils and immunologic lung disease. Med Clin North Am 65:1055, 1981
vasculitis
with
atypical
features
10. Pare JAP, Fraser RG, Hogg JC, Howlett JG, Murphy SB: Pulmonary “mainline” granulomatosis: tdlcosis of intravenous methadone abuse. Medicine 58229, 1979 11. Chumbley LC, Harrison EC Jr, DeRemee RA: Allergic granulomatosis and angiitis (Churg-Strauss syndrome). Mayo Clin Proc 521477, 1977 12. Sonin L, Patterson R: Corticosteroid-dependent asthma and schizophrenia. Arch Intern Med 144554, 1984
Prevalence of house dust mites in nursing homes in southwest Ohio 13. L. Vyszenski-Moher, M.Sc., L. G. Arlian, Ph.D., I. L. Bernstein, .J. S. Gallagher, Ph.D. Dayton and Cincinnati, Ohio
M.D., and
1)etmatophagoides spp house dust mites were found to be prevalent in geriatric nursing homes in southwestern Ohio. Mite density was lower in nursing homes than in private homes in comparable dust-sampling areas and at similar times of the year. Generally, fewer mattresses, floors, and articles ofjiirniture were mite positive in nursing homes by comparison to private homes. Lower institutional mite levels were attributed to frequent linen and mattress cover changes and rigorous cleaning practices, coupled with the lack of a favorable mite environment provided by high ambient temperatures, low relative humidity, tiled or vinyl-covered floors and furniture, and covered or encased mattresses. (J ALLERGY CLIN IMMUNOL 77:745-a, 1986.)
The house dust mites, Dermatophagoides farinae and D. ptermyssinus, have been established as the sources of major allergens for patients sensitive to house dust. These mites are most prevalent in homes in more humid geographic areas where mite density may range from a few to >18,OOO/gm of dust in specific locations within the home.’ Within the home mites are more prevalent in carpeted floor areas, fabric-upholstered furniture, and mattresses that are used most frequently, and they are rare or absent in other areas. Although this distribution and dependence on
From the Departments of Biological Sciences and Physiology, College of Science and Engineering and School of Medicine, Wright State University, Dayton, Ohio, and Department of Medicine, Division of Immunology, University of Cincinnati Medical Center, Cincinnati, Ohio. Supported by Grant ROI AI I3702 from the National Institute of Allergy and Infectious Diseases. Received for publication Sept. 24, 1985. Accepted for publication Nov. 20, 1985. Reprint requests: ;L. G. Arlian, Department of Biological Sciences and Physiology and Biophysics, Wright State University, Dayton, OH 45435.
I
I Abbreviation RH:
I
Relative
used humidity I
humans is not clearly understood, when sufficiently high RH exists in the mite microhabitat, presumably, accumulating skin scales that are shed during constant or frequent use of these areas or furniture serve as food to support mite-population development. In homes where RH is not continually or sufficiently high to support mite populations, human use of beds and furniture may provide sufficient moisture to these microhabitats to support significant mite levels, and these locations may become the major foci in the home. ’ Because of these ecologic relationships and the large amount of time institutionalized patients are confined to beds and other furniture, they could potentially provide enough dander and moisture to support large mite populations in these settings. In hospitals, despite the fact that patients are confined primarily to beds, mite prevalence is generally Iow,~-’ probably because of the high hygienic standards, plastic mat745