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Arthritis and hypergammaglobulinemic purpura in hypersensitivity pneumonitis
BRIEF CLINICAL OBSERVATIONS
Arthritis and -Hypergammaglobulinemic Purpura in Hypersensitivity Pneumonitis
n hypersensitivity pneumonitis or extrinsic allergic alveolitis, both systemic and respiratory symptoms may occur. l Two patients are reported with systemic manifestations of this disease that have not been described previously.
dard laboratory tests were normal. Serum protein was 80 gk (31%gammaglobulins).Circulating immune complexes were present. Antinuclear antibody and rheumatoid factor were negative. Chest roentgenogram showed a reticulonodular pattern. Antibodies to pigeon antigen were strongly positive. Pulmonary function tests revealed normal values except for impaired diffusion capacity (D&,, 43%). The BAL fluid showed 43% lymphocytes with a CD4KD8 ratio of 0.4. In the transbronchial biopsies, interstitial pneumonitis was seen and biopsies of the purpura revealed a leukocytoclastic vasculitis. The diagnosis of bird-breeder’s lung was made. After cessation of the exposure and initiation of prednisone therapy, clinical improvement was noted.
CASE REPORTS
DISCUSSION
Hendrika Maria Oosterkamp, MD, Hans van der Pijl, MD, Jan Derksen, MD, PhD, Luuk N.A. Willems, MD, PhD, Paul H.E.M de Meijer, MD, PhD, Leiden University Hospital,Leiden, the Netherlands
I
Case I
Besides the well-known features of hypersensitivA 51-year-old man was admitted because of dysp- ity pneumonitis, the 2 patients reported here had adnea, thoracic pain, dry cough, and weight loss of 1 ditional symptoms. Both patients exhibited hypermonth duration. He had been holding parakeets for gammaglobulinemia and purpura on the legs, while 40 years, Physical examination revealed dorsobasal the fit patient also exhibited a perivascular infiltrate pulmonary r-ales, palpable purpura on the legs, and and developed oligoarthritis and the secolnd patient also exhibited a leukocytoclastic vasculitis. swelling of both knees and the right ankle. Besides an erythrocyte sedimentation rate (ESR) Although hypergammaglobulinemia is a well of 80 mm/h, standard laboratory tests were normal. known feature of hypersensitivity pneumonitis,’ the The serum protein concentration was elevated (85 development of pm-pm-ahas not been mentioned beg/L) due to hypergammaglobulinemia with raised im- fore. Waldenstroem2 described a syndrome consistmunoglobulin A &A) (13.3 g/L) and IgG (44.9 g/L). ing of recurrent pm-pm-a, hypergammaglobulinemia, There were circulating immune complexes and com- elevated ESR, and mild anemia. The purpura seen in plement activation. Antinuclear antibody and rheu- hypergammaglobulinemia are petechial, scattered, matoid factor were negative. The arterial blood gas and usually on the legs and are brought on by standwas unremarkable. ing, walking, tight-fitting garments, and healt. The purChest roentgenogram demonstrated fine reticulopura are often accompanied by arthralgia, low-grade fever, and edema of the lower extremities.3 nodular shadows throughout both lungs. Antibodies to parakeet antigen were strongly positive. PulmoHypergammaglobulinemic purpura (HGP) is divided nary function tests revealed decreases in volume and in a primary type and a secondary type associated with an underlying disease.4Laboratory abnormalities in diffusion capacity. The bronchoalveolar lavage (BAL) fluid showed 60%lymphocytes with a CD4XD8 ratio HGP are elevated gamma globulins, elevated ESR, and of 1. Transbronchial biopsies demonstrated intersti- mild anemia.2,3Rheumatoid factor, antinuclear antitial pneumonitis. Biopsy of the purpura revealed a body, or cryoglobulinemia may be preser~t.3 Inflammation of the superficial dermal blood vessels, with perivascular infiltrate and extravasation of erythroa polymorphonuclear leucocyte infiltrate in the cytes. Joint fluid of the right knee showed 0.2 X 10a/mm3leucocytes, and synovial biopsy showed a hy- acute phase, followed by a mononuclear infiltrate is found. Red blood cell extravasation, leukocytoclaperplastic synovium. sis, and blood vessel damage have been describedThe diagnosis bird-breeder’s lung was made. After cessation of the exposure, the clinical signs disap- from arteriolar necrosis to fibrinoid degeneration.3 Olmstead et al4 found IgM and C3 deposition in peared. The chest roentgenogram and the pulmonary blood vessel walls and elevated levels of IgM and IgG function tests improved after starting prednisone. immune complexes, which supports the concept that HGP is mediated by immune complexes. I3ecause of Case II A 59year-old pigeon breeder was admitted because the clinical and laboratory abnormalities in our paof dyspnea, productive cough, general malaise, and tients, we think the pathogenesis of the purpura is night sweats of 6 months duration. There were fine identical to that described for HGP. Several concomitant phenomena (eg, arthralgia5) rales over both lungs and palpable purpura on the distal part of the legs. Besides the ESR (116 mm/h), stan- have been reported in hypersensitivity pneumonitis. 478
April
1996
The American
Journal
of Medicine@
Volume
100
BRIEF CLINICAL OBSERVATIONS
A recent case report mentions myositis and arthritis in 1 patient with this disea.se.(jIn our opinion, however, the clinical features described do not justify the diagnosis of arthritis in this patient. To our knowledge, our patient therefore, is the first described with frank arthritis. The immunologic process in the pathogenesis of HGP may also be the explanation for the development of arthritis in hypersensitivity pneumonitis. We suggest HGP and arthritis in our patients resulted from an immunologic process in which hypergammaglobulinemia and high levels of circulating immune complexes lead to deposition of immune complexes and complement with subsequent inflammation in skin vessels and joints.
REFERENCES 1. Fink JN. Hypersensitivity
pneumonitis. Clin Chest Med. 1992;13:303-309. 2. Waldenstroem J. Clinical methods for determination of hyperproteinemia their practical value for diagnosis. Nord Med. 1943;20:2288-2295.
and
3. Kyle RA, Gleich GJ, Bayrd ED, Vaughan JH. Benign hypergammaglobulinemic purpura of Waldenstroem. Medicine. 1971;50:113-123. 4. Olmstead AD, Zone JJ, LaSalle B, Krueger GG. Immune complexes in the pathogenesis
of hypergammaglobulinemic
purpura.
J Am Acad
Dermatof.
1980;3:174-179. 5. Pitcher
WD. Southwestern
Internal
Medicine
Conference:
hypersensitivity
pneumonitls. Am J Med SCI. 1990;300:251-266. 6. Lonneux M, Nolard N, PhIlIppart I, et al. A case of lymphocytic pneumonitis, myosltls and arthritis associated with exposure to Aspergrllus nlger. J Allergy Clan Immunol.
1995;95:1047-1049. Manuscript submitted August 17, 1995 and accepted in revised form October 31, 1995.
swelling, and warmth of the left forearm.. Erythema spread proximally to the olecranon bursa The patient stated that she had been increasingly leaning on her forearms and elbows to provide ventilatory support. Medications included prednisone (10 to 20 mg daily), oral theophylline, and three mini-dose inhalers. Her temperature was 98.6”F. ExtremiQv examination revealed warmth, erythema, and swelling of the left mid-forearm to the elbow. The olecranon bursa was distended, warm, and tender, with no visible skin wound or laceration. Complete blood count was remarkable for an elevated white blood cell (WBC) count of 18.2 X log/L with 88% polymoq)honuclear leukocytes. Left olecranon bursa aspiration revealed a bursal fluid WBC of 11.4 X log/L. Bursal fluid Gram’s stain showed rare intra- and extracellular gram-positive cocci with culture positive for Staphylococcus aureus. Treatment with intravenous nafcillin sodium (Unipen, Wyeth-Aye& Laboratories, Philadelphia, Pennsylvania) resulted in prompt symptom improvement. Patients with severe COPD frequently lean forward, bracing themselves on their forearms.4 .A forward, “bent” posture increases the capacity for sustained hyperpnea.5 Such a posture, with its concominant sustained pressure over the olecranon bursae, could also predispose patients with severe COPD to septic ok+ cranon bursitis.
DISCUSSION
Septic Olecranon Bursitis in Patients With Chronic Obstructive Pulmonary Disease Raymond J. Enzenauer, MD, LTC, MC, Jerry L. PIUS, DO, FCCP, LTC, MC, FitzsimonsArmy Medical Center,Aurora, Colorado eptic olecranon bursitis is seen in patients with frequent elbow trauma,’ especially middle-aged men involved in manual labor.” While immunocompromised patients with alcoholism or diabetes may be at increased risk for septic olecranon bursitis: large series do not include chronic obstructive pulmonary disease (COPD) as a risk factor for disease.‘.” We report a 74-yearald woman with severe COPD and septic olecranon bursitis. The forward-leaning posture in patients with severe COPD may be a risk factor predisposing to olecranon bursal infection.
S
CASE REPORT A 74year-old woman with severe oxygen-dependent COPD was admitted with 1 week of increasing pain,
The case presented is clearly atypical demographically. Septic bursitis is a diseaseof middle-aged manual laborers.’ Mean age is 47 years,’ with up to 100% of patients being men.” Typically patients with severe COPD are older, with no significant male predominance. Other factors, such as uremia, diabetes, and alcoholism may increase host susceptibility to bursal infection.’ Corticosteroid therapy may increase the risk of septic olecranon bursitis in patients without COPD. ‘13Accidental trauma, be it direct, repetitive minor trauma or constant pressure, appears to be the common demoninator. ’ Hemorrhagic olecranon bursitis, or “dialysis elbow” has been reported in uremic patients as a result of prolonged pressure against the olecranon process during dialysis.6 Local or distant skin disruption may not be present in 42%.’ Even when visible skin wounds are not apparent, the avenue of bacterial introduction is presumed to be through the skin. ’ A high index of suspicion should prompt bursal aspiration when the diagnosis of septic olecranon bursitis is entertained. Bursal fluid WBC counts in septic bursitis are lower than those in septic arthritis.2 Bacteria may be seen on Gram’s stain smears in only 65% of culture-positive bursal fluids.’ S auwus is tlne infecting organism in the majority of cases.2 April
1996
The American
Journal
of Medicine@
Volume
100
479
Arthritis and -Hypergammaglobulinemic Purpura in Hypersensitivity Pneumonitis
n hypersensitivity pneumonitis or extrinsic allergic alveolitis, both systemic and respiratory symptoms may occur. l Two patients are reported with systemic manifestations of this disease that have not been described previously.
dard laboratory tests were normal. Serum protein was 80 gk (31%gammaglobulins).Circulating immune complexes were present. Antinuclear antibody and rheumatoid factor were negative. Chest roentgenogram showed a reticulonodular pattern. Antibodies to pigeon antigen were strongly positive. Pulmonary function tests revealed normal values except for impaired diffusion capacity (D&,, 43%). The BAL fluid showed 43% lymphocytes with a CD4KD8 ratio of 0.4. In the transbronchial biopsies, interstitial pneumonitis was seen and biopsies of the purpura revealed a leukocytoclastic vasculitis. The diagnosis of bird-breeder’s lung was made. After cessation of the exposure and initiation of prednisone therapy, clinical improvement was noted.
CASE REPORTS
DISCUSSION
Hendrika Maria Oosterkamp, MD, Hans van der Pijl, MD, Jan Derksen, MD, PhD, Luuk N.A. Willems, MD, PhD, Paul H.E.M de Meijer, MD, PhD, Leiden University Hospital,Leiden, the Netherlands
I
Case I
Besides the well-known features of hypersensitivA 51-year-old man was admitted because of dysp- ity pneumonitis, the 2 patients reported here had adnea, thoracic pain, dry cough, and weight loss of 1 ditional symptoms. Both patients exhibited hypermonth duration. He had been holding parakeets for gammaglobulinemia and purpura on the legs, while 40 years, Physical examination revealed dorsobasal the fit patient also exhibited a perivascular infiltrate pulmonary r-ales, palpable purpura on the legs, and and developed oligoarthritis and the secolnd patient also exhibited a leukocytoclastic vasculitis. swelling of both knees and the right ankle. Besides an erythrocyte sedimentation rate (ESR) Although hypergammaglobulinemia is a well of 80 mm/h, standard laboratory tests were normal. known feature of hypersensitivity pneumonitis,’ the The serum protein concentration was elevated (85 development of pm-pm-ahas not been mentioned beg/L) due to hypergammaglobulinemia with raised im- fore. Waldenstroem2 described a syndrome consistmunoglobulin A &A) (13.3 g/L) and IgG (44.9 g/L). ing of recurrent pm-pm-a, hypergammaglobulinemia, There were circulating immune complexes and com- elevated ESR, and mild anemia. The purpura seen in plement activation. Antinuclear antibody and rheu- hypergammaglobulinemia are petechial, scattered, matoid factor were negative. The arterial blood gas and usually on the legs and are brought on by standwas unremarkable. ing, walking, tight-fitting garments, and healt. The purChest roentgenogram demonstrated fine reticulopura are often accompanied by arthralgia, low-grade fever, and edema of the lower extremities.3 nodular shadows throughout both lungs. Antibodies to parakeet antigen were strongly positive. PulmoHypergammaglobulinemic purpura (HGP) is divided nary function tests revealed decreases in volume and in a primary type and a secondary type associated with an underlying disease.4Laboratory abnormalities in diffusion capacity. The bronchoalveolar lavage (BAL) fluid showed 60%lymphocytes with a CD4XD8 ratio HGP are elevated gamma globulins, elevated ESR, and of 1. Transbronchial biopsies demonstrated intersti- mild anemia.2,3Rheumatoid factor, antinuclear antitial pneumonitis. Biopsy of the purpura revealed a body, or cryoglobulinemia may be preser~t.3 Inflammation of the superficial dermal blood vessels, with perivascular infiltrate and extravasation of erythroa polymorphonuclear leucocyte infiltrate in the cytes. Joint fluid of the right knee showed 0.2 X 10a/mm3leucocytes, and synovial biopsy showed a hy- acute phase, followed by a mononuclear infiltrate is found. Red blood cell extravasation, leukocytoclaperplastic synovium. sis, and blood vessel damage have been describedThe diagnosis bird-breeder’s lung was made. After cessation of the exposure, the clinical signs disap- from arteriolar necrosis to fibrinoid degeneration.3 Olmstead et al4 found IgM and C3 deposition in peared. The chest roentgenogram and the pulmonary blood vessel walls and elevated levels of IgM and IgG function tests improved after starting prednisone. immune complexes, which supports the concept that HGP is mediated by immune complexes. I3ecause of Case II A 59year-old pigeon breeder was admitted because the clinical and laboratory abnormalities in our paof dyspnea, productive cough, general malaise, and tients, we think the pathogenesis of the purpura is night sweats of 6 months duration. There were fine identical to that described for HGP. Several concomitant phenomena (eg, arthralgia5) rales over both lungs and palpable purpura on the distal part of the legs. Besides the ESR (116 mm/h), stan- have been reported in hypersensitivity pneumonitis. 478
April
1996
The American
Journal
of Medicine@
Volume
100
BRIEF CLINICAL OBSERVATIONS
A recent case report mentions myositis and arthritis in 1 patient with this disea.se.(jIn our opinion, however, the clinical features described do not justify the diagnosis of arthritis in this patient. To our knowledge, our patient therefore, is the first described with frank arthritis. The immunologic process in the pathogenesis of HGP may also be the explanation for the development of arthritis in hypersensitivity pneumonitis. We suggest HGP and arthritis in our patients resulted from an immunologic process in which hypergammaglobulinemia and high levels of circulating immune complexes lead to deposition of immune complexes and complement with subsequent inflammation in skin vessels and joints.
REFERENCES 1. Fink JN. Hypersensitivity
pneumonitis. Clin Chest Med. 1992;13:303-309. 2. Waldenstroem J. Clinical methods for determination of hyperproteinemia their practical value for diagnosis. Nord Med. 1943;20:2288-2295.
and
3. Kyle RA, Gleich GJ, Bayrd ED, Vaughan JH. Benign hypergammaglobulinemic purpura of Waldenstroem. Medicine. 1971;50:113-123. 4. Olmstead AD, Zone JJ, LaSalle B, Krueger GG. Immune complexes in the pathogenesis
of hypergammaglobulinemic
purpura.
J Am Acad
Dermatof.
1980;3:174-179. 5. Pitcher
WD. Southwestern
Internal
Medicine
Conference:
hypersensitivity
pneumonitls. Am J Med SCI. 1990;300:251-266. 6. Lonneux M, Nolard N, PhIlIppart I, et al. A case of lymphocytic pneumonitis, myosltls and arthritis associated with exposure to Aspergrllus nlger. J Allergy Clan Immunol.
1995;95:1047-1049. Manuscript submitted August 17, 1995 and accepted in revised form October 31, 1995.
swelling, and warmth of the left forearm.. Erythema spread proximally to the olecranon bursa The patient stated that she had been increasingly leaning on her forearms and elbows to provide ventilatory support. Medications included prednisone (10 to 20 mg daily), oral theophylline, and three mini-dose inhalers. Her temperature was 98.6”F. ExtremiQv examination revealed warmth, erythema, and swelling of the left mid-forearm to the elbow. The olecranon bursa was distended, warm, and tender, with no visible skin wound or laceration. Complete blood count was remarkable for an elevated white blood cell (WBC) count of 18.2 X log/L with 88% polymoq)honuclear leukocytes. Left olecranon bursa aspiration revealed a bursal fluid WBC of 11.4 X log/L. Bursal fluid Gram’s stain showed rare intra- and extracellular gram-positive cocci with culture positive for Staphylococcus aureus. Treatment with intravenous nafcillin sodium (Unipen, Wyeth-Aye& Laboratories, Philadelphia, Pennsylvania) resulted in prompt symptom improvement. Patients with severe COPD frequently lean forward, bracing themselves on their forearms.4 .A forward, “bent” posture increases the capacity for sustained hyperpnea.5 Such a posture, with its concominant sustained pressure over the olecranon bursae, could also predispose patients with severe COPD to septic ok+ cranon bursitis.
DISCUSSION
Septic Olecranon Bursitis in Patients With Chronic Obstructive Pulmonary Disease Raymond J. Enzenauer, MD, LTC, MC, Jerry L. PIUS, DO, FCCP, LTC, MC, FitzsimonsArmy Medical Center,Aurora, Colorado eptic olecranon bursitis is seen in patients with frequent elbow trauma,’ especially middle-aged men involved in manual labor.” While immunocompromised patients with alcoholism or diabetes may be at increased risk for septic olecranon bursitis: large series do not include chronic obstructive pulmonary disease (COPD) as a risk factor for disease.‘.” We report a 74-yearald woman with severe COPD and septic olecranon bursitis. The forward-leaning posture in patients with severe COPD may be a risk factor predisposing to olecranon bursal infection.
S
CASE REPORT A 74year-old woman with severe oxygen-dependent COPD was admitted with 1 week of increasing pain,
The case presented is clearly atypical demographically. Septic bursitis is a diseaseof middle-aged manual laborers.’ Mean age is 47 years,’ with up to 100% of patients being men.” Typically patients with severe COPD are older, with no significant male predominance. Other factors, such as uremia, diabetes, and alcoholism may increase host susceptibility to bursal infection.’ Corticosteroid therapy may increase the risk of septic olecranon bursitis in patients without COPD. ‘13Accidental trauma, be it direct, repetitive minor trauma or constant pressure, appears to be the common demoninator. ’ Hemorrhagic olecranon bursitis, or “dialysis elbow” has been reported in uremic patients as a result of prolonged pressure against the olecranon process during dialysis.6 Local or distant skin disruption may not be present in 42%.’ Even when visible skin wounds are not apparent, the avenue of bacterial introduction is presumed to be through the skin. ’ A high index of suspicion should prompt bursal aspiration when the diagnosis of septic olecranon bursitis is entertained. Bursal fluid WBC counts in septic bursitis are lower than those in septic arthritis.2 Bacteria may be seen on Gram’s stain smears in only 65% of culture-positive bursal fluids.’ S auwus is tlne infecting organism in the majority of cases.2 April
1996
The American
Journal
of Medicine@
Volume
100
479