Multiple Aortic Aneurysms
PAUL R CIPRIANO, DANIEL R ALONSO, HAROLD
A
BALTAXE,
WILLIAM A GAY, JAMES P SMITH, New
MD* MD
JR, MD
MD MD
York. New York
in Relapsing Polychondritis
A patient with relapsing polychondritis and thoracic and abdominal aortic aneurysms is described. The aortic changes were due to aortitis, which primarily involved the media, with increased vascularization, perivascular infiltration of mononuclear cells, increased amounts of collagen and decreased amounts of elastic tissue and sulfated acid mucopolysaccharides. Aortic aneurysms frequently occur in relapsing polychondritis; they are usually in the ascending aorta but may be multiple and involve the abdominal aorta; involvement of the ascending aorta results in aortic regurgitation and left ventricular failure, and involvement of the abdominal aorta may be clinically silent and result in fatal rupture.
Relapsmg polychondritlsi is an uncommon but climcally distinctive systemic disease characterized by intermittent inflammation of cartilaginous structures in the ears, nose, Joints, larynx and trachea. Its onset usually occurs in the 3rd through 6th decades, and it is often fatal within several years. 2p3Since Pearson et a1.4 recogmzed aortic disease as a complication of this disorder m 1967, nine patients with relapsing polychondritis and aortic aneurysm have been described.3mg This communication (1) describes a patient who had coexisting thoracic and abdominal aortic aneurysms shortly after the onset of relapsing polychondritis, and (2) reviews the clinical and pathologic features of aortic disease associated with relapsing polychondritls.
Case Report
From the Departments of RadIology, Pathology, Surgery and Medlclne, New York Hospital-Cornell Medtcal Center, New York, N Y This study was partially supported by Grant 1 TO 1 HL05966-02 CAR from the Natlonal lnstltutes of Health, Bethesda, Md Manuscript accepted April 2, 1975 * Present address and address for reprints Paul R Ciprlano, MD, Stanford University School of Medicine, Dlvlsron of Cardiovascular Radiology, Stanford, Callf 94305
A 37 year old woman was hosprtahzed at New York Hosprtal m December 1972 after an acute febrrle illness of 3 weeks’ duration characterized by fever to 102 “F, severe migratory arthralglas and myalgias and pharyngitis with pam radiating to the right ear She complained primarily of pam m the right side of the neck and face and noted auditory impairment on the rrght side, postural drzzmess and mild photophobia She had undergone radical mastectomy m 1964 for infiltrating duct carcmoma but had no evidence of recurrent disease A stepsister had rheumatoid arthritis Exammatron revealed an absent right gag reflex, tender right sternoclerdomastold and trapezrus muscles, and a Weber’s test with locahzatioh to the right side Laboratory studies revealed an elevated erythrocyte sedimentation rate (34 to 44 mm m 1 hour, Wmtrobe), slightly low gamma-M globulm (44 mg/lOO ml of plasma) and elevated alpha2 globulin levels with no monoclonal component Other studies, including complete blood count, urinalysis, Venereal Disease Research Laboratory study antinuclear antibodies, latex fixation, direct and indirect Coombs tests, lupus erythematosus preparations, chest roentgenograms, lumbar puncture, audiogram and electroencephalogram revealed normal or negative findings An electromyogram demonstrated mild partial denervatron of the right sternocleidomastord and trapezms muscles. Biopsy of the temporal artery was performed, although the vessel was not tender. The media of the temporal artery was focally absent, which allowed approxrmatron of the internal and external elastrc lammae (Fig 1A). The internal elastic lamma was focally interrupted m some areas and reduplicated m others The intrma was focally thickened No grant cells or thrombl were seen These morphologic features were interpreted as consistent with healed vasculitrs Her symptoms responded to predmsone, 40 mg/day
June 1976
The American Journal of CARDIOLOGY
Volume 37
1097
RELAPSING POLYCHONDRITIS -CIPRIANO
ET At
FIGURE 1. Hlstologlc sectlons A, temporal artery with focal atrophy of the media, interruptlon of the internal elastic lamina and intlmal thickening B, subcutaneous nodule demonstrating an acute necrotizlng panarterltls (Elastica-van Gleson stain. X40, reduced by 47 percent )
FIGURE 2 Photograph showing saddle deformity of the nose and ring of scleromalacia of the left eye
Clinical course: After admmlstratlon of predmsone was dlscontmued, migratory arthralglas recurred m January 1973, accompanied by a low grade fever and small painful subcutaneous nodules over the volar surface of both arms, the posterior surface of both legs and the heels In March 1973, a tender nodule, similar m character to the subcutaneous nodules on the arms and legs, appeared on the bridge of the nose Eplsclerltls of the left eye followed shortly thereafter Biopsy of a subcutaneous nodule on the right ankle revealed an acute necrotlzmg panvascuhtls that prlmarlly involved arteries (Fig 1B) With admmlstratlon of large doses of cortlcosterolds (predmsone, 80 mg/day), the fever and subcutaneous nodules disappeared Predmsone therapy was decreased gradually but not dlscontmued In May 1973, the patlent was hospltahzed at another hospital with eplsclerltls of the left eye, recurrent fever and painful knees and ankles By then she had a saddle deformity of the nose and scleromalacla Results of extensive laboratory studies were normal except for a white blood count of 14,700 (70 percent polymorphonuclear leukocytes, 25 percent lym-
1098
June 1976
the
Amencan
Journal
of CARDIOLOGY
Volume
phocytes and 5 percent monocytes), an erythrocyte sedlmentatlon rate of 66 mm m 1 hour and a blood glucose level of 228 mg/lOO ml She was treated with predmsone (60 mg/ day), chloroqume (500 mg/day) and lsomazlde (300 mg/day) In January 1974, while she was St.111receiving predmsone therapy, the left vocal cord became paralyzed Chest roentgenograms demonstrated a small aneurysm of the proximal descending thoraclc aorta Recurrent sharp substernal pain developed m April 1974 and m June 1974 she was readmitted to New York Hospital with severe pam m the left side of the chest She was afebrlle Physzcal examnat~on revealed a blood pressure of 112/74 mm Hg, a blue rmg of scleromalacla of the left eye, an early cataract of the right eye and a saddle nose (Fig 2), there was no deformity of the ears The erythrocyte sedlmentatlon rate was 38 mm m 1 hour, results of all other laboratory tests were normal Chest roentgenograms demonstrated a round mass, approximately 5 cm m diameter, at the aortlc arch and a poorly clrcumscrlbed density m the left upper lung An aortogram demonstrated a saccular aneurysm of the proximal descendmg thoraclc aorta that measured 5 cm m diameter (Fig 3A), and a fuslform aneurysm of the abdominal aorta below the renal arteries that measured 9 by 3 5 cm (Fig 38) The aortlc valve functioned normally, and the unmvolved aorta was normal m cahber and had a smooth lumen At operatzon, the saccular aneurysm commumcated with the aorta through a 1 by 2 cm elhpsold opening opposite the left subclavlan artery The aneurysm was incised and Its opening mto the aorta was patched with Dacron@, no aortlc tissue was removed The edge of the orlflce of the aneurysm felt thick and fibrotic, but the remainder of the vlsuabzed aorta appeared normal Biopsy of the radlographlcally demonstrated density m the left lung showed that it was a pulmonary infarct without evidence of pulmonary vasculltls After an uneventful postoperative recovery, the patient was discharged on a regimen of predmsone (25 mg/day), chloroqume (500 mg/day) and lsomazide (300 mg/day) In August 1974 she was readmitted because of contmuous lower abdominal pam that radiated to the back Retroperltoneal bleeding was found at operation, and the posterior wall of the abdominal aortlc aneurysm was necrotic and ulcerated The remainder of the abdominal aorta appeared normal A Dacron aortlc graft was successfully inserted, and to date her recovery has been uneventful
37
RELAPSING POLYCHONDRIT~S-CIPRIANO ET AL
FIGURE 3. Aortograms. A, thoracic aortogram in the left anterior oblique projection demonstrating a 5 cm saccular aneurysm in the proximal descending thoracic aorta. 6, abdominal aortogram demonstrating a 9 by 3.5 cm fusiform aneurysm of the abdominal aorta below the renal arteries.
FIGURE 4. Histologic sections of the abdominal aortic aneurysm. A, media demonstrating extensive loss and fragmentation of elastic fibers, deposition of collagen and mononuclear cell infiltrates. B, outer media demonstrating perivascular mononuclear cell infiltrates and dense collagenous scarring. C, scarred adventitia showing prominent mononuclear cell infiltrates adjacent to patent vasa vasorum. (Elastica-van Gieson (A) and hematoxylin-eosin stains; all X40, reduced by 46 percent .)
June 1976
The American Journal of CARDIOLOGY
Volume 37
1099
I
M
M
M
M
F
F
M
M
5
4
3
4
9
8
7
5
*
2
3
4
5
6
7
8
9
10
37
89
57
39
35
33
29
22
21
19
At Onset of RPC ______
38 2
92
573
48
36 7
39 7
44
23 7
25
19 2
+
+
+
+
+
_
+ _
+
+
_
+
_
__
+
+
+
_
_
_ _
+ _
+ _
f _
_
Dlastollc
systollc
Cardlomegaly ~~.___ +
Aortlc Valve Murmur
and Aortlc
_
_
0
?“A-V block 0
_
+
+
0
+
+ 1” and 2’ A-V block
0
+
-
1’ A-V block _
ECG
+
LV Failure
Aneurysms
Desc Th Ao and Lower Abd Ao
Asc Ao dlssectlon Desc Th Ao
Asc, Ao, arch and Desc Ao Desc Th Ao and upper Abd Ao
Asc Ao
Asc Ao and lower Abd Ao
Asc Ao and arch
Prox Asc Ao Lowe1 Abd Ao
site of Aneurysm ____ ~~
ears
Nose
Ears
Ears
ear, costochondrltls Ears, nose, trachea
Nose,
Nose,
Nose, ears, costochondrltls Nose, eats
Nose. ears
Nose, knees
Sttesof Chondrltts I_. __-
Eplsclerltls, retlnal detach ment,rheumatold arthrltls Eplsclerltls, scleromalacla, subcutaneous nodules, mlgratory arthralglas, cataract __--
tts
ConJunctlvl-
Eplsclerltls, muscle atrophy
Eplsclerms, migratory arthralglas Eplsclerltls
Eplscterltls, subcutaneous nodule, arthropathy, amputatlon of leg due to vasculltls Eplsclerltls, vertigo, deafness Serous otltls media, vertigo, eplsclerltls
Eplsclerltls
Associated Involvement ~_
dtd
CS, CLQ, Th and Abd Ao aneurysms repalred, doing well
CS, reportedly did well Aneurysm repaired, reportedly did well
CS, reportedly well
CS, 6MP. AVR, doing well 6 mo later CS. AZT. AVR, died 22 mo later of ruptured Abd Ao aneurysm CS, AVP, died suddenly 18 mo later CS, IMC, reportedly did well
CS, dted of LV failure CS, died of ruptured Abd Ao aneurysm
Treatment and ClInIcal Course __-___
+ = present, - = absent, 0 = data not available, Abd = abdoml?al, AO = aorta, Asc = ascending, AVP = Aoltlc valvuloplasty, AVR = aortlc valve replacement, A - V = atrIoventrlcular, AZT = azathloprlne, CLQ = chloroqulne, CS = cortlcosterold, Desc = descending, ECG = electrocardiogram, IMC = Indomethacln, LV = left ventricular, 6MP = 6 mercaptopurlne, mo = months, prox = proximal, RPC = relapsing polychondrltcs, Th = thoraclc
F
M
Sex __.~.
6
Reference
Aor t&c Aneurysm Detected
(yr)
Relapsmg Polychondrltls
Age
Features of Patients With _
1
CaSe “0
TABLE Clmlcal
RELAPSING
The media of the abdomuzal aortlc &sue removed atoperatlon was thinned and distorted by extensive loss and fragmentation of elastic fibers (Fig 4A) and deposltlon of collagen (Fig 4, A and B) The outer media showed increased vascularlzatlon and perlvascular mononuclear cell infiltrates (Fig 4B) The adventltla was densely scarred with collagen and it contained focal mononuclear cell infiltrates adjacent to patent vasa vasorum (Fig 4C) These hlstologlc findings are similar to those described In patients with relapsing polychondrltls and aortltls 3,4,10~11
Discussion The development of aortic aneurysms is a potentially fatal complication of relapsing polychondrltls, occurring in approximately 10 percent of patients,” and fatal rupture of clinically unsuspected aortic aneurysms has been found m this dlsease.3,5 Destruction of the media of the aorta, without aortlc dilatation, also has been reported m relapsing polychondritis lo,11
Histopathology: Relapsing polychondritls 1s characterized morphologically by inflammation of cartilage and by vascubtls localized to tissues with high concentrations of glycosammoglycans 3 Grossly, the aortic lesions appear to be focal, however, loss of all classes of glycosaminoglycans has been demonstrated histochemically throughout aortlc tissue that grossly and histologically appeared normal. The aortltis primarily mvolves the media, with increased vascularlzatlon, perlvascular mflltratlon of mononuclear cells, increased amounts of collagen and decreased amounts of elastic tissue and sulfated acid mucopolysaccharldes 4 The hlstopathologlc appearance of the aortic lesions m relapsing polychondrltls is distinct from that m Erdhelm’s cystic medial necrosis, Marfan’s syndrome, syphilitic aortltls and giant cell aortltls.4J’ The loss of glycosaminoglycans and the inflammatory reaction m the aorta have been considered secondary to the release of lysosomal enzymes from damaged cells 4 This concept has been supported by work showing that destructlon of cartilage and aortic media can be produced in rabbits by the intravenous mJectlon of crude papain 13Although the factors leading to cell damage m relapsing polychondritls remam unknown, It has been proposed that antlcartilage antlbodies,ni preclpitms against chondroitm sulfatel” and lymphocyte sensltlzatlon to chondromucoprotems15 are involved m the mechanism of the disease process Clinical features: Including our patient, 10 patients (7 men and 3 women aged 19 to 92 years, average 38 years) have been described as having aortlc aneurysms due to relapsing polychondrltls (Table I) J-g Aortlc disease became apparent from 3 months to 15 years (average 4.5 years) after the onset of symptoms of relapsing polychondritls, in five patients it was noted within 2 years Aortlc aneurysms developed most frequently m the ascending aorta (SIX patients: Cases 1,3, 4,5,6 and 8) Four of these SIX patients (Cases 1,3,5 and 6) were less than 40 years old when the aneurysms were detected. Three of the six patients with relapsing polychondritis and aneurysms of the ascending aorta also
POLYCHONDRITIS-CIPRIANO
ET
AL
had aneurysms of the abdominal aorta (Cases 1 and 2) or of the descending thoracic aorta (Case 6). All six patients with aneurysms of the ascending aorta had aortlc diastolic murmurs and left ventricular failure, five (Cases 1, 3, 4, 5 and 8) had cardlomegaly, and three (Cases 1, 4 and 8) had first or second degree atnoventrlcular block. None of these physical findings developed in the remaining four patients, who had mvolvement of the descending thoracic aorta (Case 9), the abdominal aorta (Case 2), or both (Cases 7 and lo), but not of the ascending aorta Thus, the cardiac clinical findings m patients with relapsing polychondrltls and aortlc aneurysms clearly differ depending upon whether or not the ascending aorta 1s involved The aortlc regurgitation is usually due to dilatation of the aortlc valve ring,3*4.11J6 alth ough thickening and retraction of the aortlc valve leaflets have been reported,” I7 and leads to left ventricular failure The conduction disturbances are probably due to extension of aortltls into the area of the bundle of His Treatment: Of the six patients with relapsing polychondritls and aneurysms of the ascending aorta, three (Cases 1, 6 and 8) were treated medically and three (Cases 3 to 5) underwent operation Of the three patients treated medically, one (Case 1) died of left ventricular failure and the other two (Cases 6 and 8) survived although Patient 8 had dissection of the ascending aorta. Two patients (Cases 3 and 4) underwent aortlc valve replacement, and the other (Case 5) had aortlc valvuloplasty Patient 4 died of rupture of a clinically unsuspected abdominal aortlc aneurysm 22 months after aortic valve replacement Patient 5 died suddenly of unknown cause 18 months after operation and Patient 3 was reported to be doing well 6 months after operation Of the four patients with relapsing polychondrltis and aneurysms not mvolvmg the ascending aorta, two (Cases 2 and 7) were treated medically. Patient 2 died of rupture of an abdominal aortlc aneurysm that had not been suspected clmically and Patient 7 had aneurysms m the descending thoraclc aorta and abdominal aorta and was reported to survive The other two of these four patients (Cases 9 and 10) survived surgical repair of aneurysms that involved the descending thoracic aorta m both and also the abdominal aorta m Case 10 Thus, four of the 10 patients with relapsing polychondrltls and aortlc aneurysms died. Two patients died of rupture of unsuspected aneurysms of the abdominal aorta, one of left ventricular failure and one of unknown cause No operative deaths or comphcatlons of surgery were reported The follouxng conclusions can be drawn from the data reuewed above (1) Aortic aneurysms are a relatively frequent complication of relapsing polychondntls; (2) these aneurysms occur most frequently m the as-
cending aorta but may be multiple and involve the abdominal aorta, (3) mvolvement of the ascending aorta results m aortlc regurgltatlon and left ventricular fallure; and (4) involvement of the abdominal adrta may be clmlcally silent and may result in fatal rupture
June 1976
The American Journal of CARDIOLOGY
Volume 37
1101
RELAPSING POLYCHONDRITIS-CIPRIANO
ET AL
Addendum In April 1975 the patient was readmitted to New York Hospital with sharp thoracolumbar pam of 4 days’ duration and a low grade fever A complete blood count was normal, but an erythrocyte sedimentation rate was 99 mm m 1 hour She had been taking predmsone (35 mg/day) before admission Thoracic and abdominal
aortlc arterlograms demonstrated the site of the patched thoraclc aortic aneurysm and a fusiform aneurysm of the abdommal aorta that began at the lower border of the abdommal aortic graft and involved both the left and the right common iliac arteries This new abdominal aortic aneurysm was repaired with a Y-shaped Dacron graft, without complication
References Pearson CM, Kkne HM, Newcomer VD Relapsrng polychondrrbs N Engl J Med 263 51-58, 1960 Dolan DL, Lemmon GB Jr, Teitelbaum SL: Relapsrng polychondrrtrs analytrcal literature revrew and studies on pathogenesrs Am J Med 41 285-299, 1966 Hughes RAC, Berry CL, Setfert M, et al: Relapsing polychondrrtrs three cases with a clrnrco-pathologrcal study and literature review 0 J Med 163 363-380, 1972 Pearson CM, Droening R, Verity MA, et al. Aorbc rnsuffrcrency and aor-bc aneurysm In relapsing polychondrrtrs Trans Assoc Am Physrcrans 80 71-90, 1967 Anderson B .Sr Ocular lessonsIn relapsrng polychondritrsand other rheumatord syndromes Am J Ophthalmol 64 35-50, 1967 Marquis Y, Rrchardson JB, Ritchre AC, et al. ldropathrc medial aortopathy and arteropathy Am J Med 44 939-954, 1968 Harner JW, Hamilton GW Aortrc abnormalities in relapsing polychondrrtrs report of a case wrth drssectrngaortrc aneurysm N Engl J Med 280 1166-l 168, 1969 Lang HD, Muller D, Ftnke J: Rezrdrvrerende Polychondrrtrs mrt Aortenaneurysrmen Dtsch Med Wochenschr 94 2033-2040, 1969 Owens DS Jr, lrby R, Toone EmRelapsng polychondrrtrswith aortrc involvement Arthritis Rheum 13 877-881, 1970
1102
June 1976
The American Journal of CARDIOLOGY
IO
11 12 13
14
15
16
17
Volume 37
Self J, Hammarsteln JF, Lyne B, et al: Relapsing polychondrrbs Arch Intern Med 120 109-112, 1967 Pappas G, Johnson M- Mitral and aot-bc valvular rnsuffrcrency In chronic relapsing polychondrrtrs Arch Surg 104 712-714, 1972 Hunder GG, Ward LE, Burbank MK: Grant cell arterrtrs producing an aortrc arch syndrome Ann Intern Med 66 578-582, 1967 Thomas L. Reversible collapse of rabbit ears after Intravenous papain, and prevention of recovery by cortrsone J Exp Med 104 245-252, 1956 Glynn LE, Holborow EJ: Conversion of trssue polysaccharides to auto-antigens by group A beta hemolytrc streptococcr Lancet 2 449-451.1952 Herman JH, Hess EV: lmmunopathologrc studres In relapsing polychondrrtrs (abstr 12 4) Abstracts of the VII European Rheumatology Congress, Brrghton, England, 1971 Yamazakt N, Garvata K, Hannya H, et al* A case of relapsing polychondrrtrs associated with aorbc tnsuffrciency Jap Heart J 7 188-195, 1966 Alexander CS, Derr RF, Sako Y. Abnormal ammo acrd composrtron of mitral and aortic valves replaced In a patient wrth chronrc relapsing polychrondrrtrs (abstr) Am J Cardrol 25 81, 1970
PAUL R CIPRIANO, DANIEL R ALONSO, HAROLD
A
BALTAXE,
WILLIAM A GAY, JAMES P SMITH, New
MD* MD
JR, MD
MD MD
York. New York
in Relapsing Polychondritis
A patient with relapsing polychondritis and thoracic and abdominal aortic aneurysms is described. The aortic changes were due to aortitis, which primarily involved the media, with increased vascularization, perivascular infiltration of mononuclear cells, increased amounts of collagen and decreased amounts of elastic tissue and sulfated acid mucopolysaccharides. Aortic aneurysms frequently occur in relapsing polychondritis; they are usually in the ascending aorta but may be multiple and involve the abdominal aorta; involvement of the ascending aorta results in aortic regurgitation and left ventricular failure, and involvement of the abdominal aorta may be clinically silent and result in fatal rupture.
Relapsmg polychondritlsi is an uncommon but climcally distinctive systemic disease characterized by intermittent inflammation of cartilaginous structures in the ears, nose, Joints, larynx and trachea. Its onset usually occurs in the 3rd through 6th decades, and it is often fatal within several years. 2p3Since Pearson et a1.4 recogmzed aortic disease as a complication of this disorder m 1967, nine patients with relapsing polychondritis and aortic aneurysm have been described.3mg This communication (1) describes a patient who had coexisting thoracic and abdominal aortic aneurysms shortly after the onset of relapsing polychondritis, and (2) reviews the clinical and pathologic features of aortic disease associated with relapsing polychondritls.
Case Report
From the Departments of RadIology, Pathology, Surgery and Medlclne, New York Hospital-Cornell Medtcal Center, New York, N Y This study was partially supported by Grant 1 TO 1 HL05966-02 CAR from the Natlonal lnstltutes of Health, Bethesda, Md Manuscript accepted April 2, 1975 * Present address and address for reprints Paul R Ciprlano, MD, Stanford University School of Medicine, Dlvlsron of Cardiovascular Radiology, Stanford, Callf 94305
A 37 year old woman was hosprtahzed at New York Hosprtal m December 1972 after an acute febrrle illness of 3 weeks’ duration characterized by fever to 102 “F, severe migratory arthralglas and myalgias and pharyngitis with pam radiating to the right ear She complained primarily of pam m the right side of the neck and face and noted auditory impairment on the rrght side, postural drzzmess and mild photophobia She had undergone radical mastectomy m 1964 for infiltrating duct carcmoma but had no evidence of recurrent disease A stepsister had rheumatoid arthritis Exammatron revealed an absent right gag reflex, tender right sternoclerdomastold and trapezrus muscles, and a Weber’s test with locahzatioh to the right side Laboratory studies revealed an elevated erythrocyte sedimentation rate (34 to 44 mm m 1 hour, Wmtrobe), slightly low gamma-M globulm (44 mg/lOO ml of plasma) and elevated alpha2 globulin levels with no monoclonal component Other studies, including complete blood count, urinalysis, Venereal Disease Research Laboratory study antinuclear antibodies, latex fixation, direct and indirect Coombs tests, lupus erythematosus preparations, chest roentgenograms, lumbar puncture, audiogram and electroencephalogram revealed normal or negative findings An electromyogram demonstrated mild partial denervatron of the right sternocleidomastord and trapezms muscles. Biopsy of the temporal artery was performed, although the vessel was not tender. The media of the temporal artery was focally absent, which allowed approxrmatron of the internal and external elastrc lammae (Fig 1A). The internal elastic lamma was focally interrupted m some areas and reduplicated m others The intrma was focally thickened No grant cells or thrombl were seen These morphologic features were interpreted as consistent with healed vasculitrs Her symptoms responded to predmsone, 40 mg/day
June 1976
The American Journal of CARDIOLOGY
Volume 37
1097
RELAPSING POLYCHONDRITIS -CIPRIANO
ET At
FIGURE 1. Hlstologlc sectlons A, temporal artery with focal atrophy of the media, interruptlon of the internal elastic lamina and intlmal thickening B, subcutaneous nodule demonstrating an acute necrotizlng panarterltls (Elastica-van Gleson stain. X40, reduced by 47 percent )
FIGURE 2 Photograph showing saddle deformity of the nose and ring of scleromalacia of the left eye
Clinical course: After admmlstratlon of predmsone was dlscontmued, migratory arthralglas recurred m January 1973, accompanied by a low grade fever and small painful subcutaneous nodules over the volar surface of both arms, the posterior surface of both legs and the heels In March 1973, a tender nodule, similar m character to the subcutaneous nodules on the arms and legs, appeared on the bridge of the nose Eplsclerltls of the left eye followed shortly thereafter Biopsy of a subcutaneous nodule on the right ankle revealed an acute necrotlzmg panvascuhtls that prlmarlly involved arteries (Fig 1B) With admmlstratlon of large doses of cortlcosterolds (predmsone, 80 mg/day), the fever and subcutaneous nodules disappeared Predmsone therapy was decreased gradually but not dlscontmued In May 1973, the patlent was hospltahzed at another hospital with eplsclerltls of the left eye, recurrent fever and painful knees and ankles By then she had a saddle deformity of the nose and scleromalacla Results of extensive laboratory studies were normal except for a white blood count of 14,700 (70 percent polymorphonuclear leukocytes, 25 percent lym-
1098
June 1976
the
Amencan
Journal
of CARDIOLOGY
Volume
phocytes and 5 percent monocytes), an erythrocyte sedlmentatlon rate of 66 mm m 1 hour and a blood glucose level of 228 mg/lOO ml She was treated with predmsone (60 mg/ day), chloroqume (500 mg/day) and lsomazlde (300 mg/day) In January 1974, while she was St.111receiving predmsone therapy, the left vocal cord became paralyzed Chest roentgenograms demonstrated a small aneurysm of the proximal descending thoraclc aorta Recurrent sharp substernal pain developed m April 1974 and m June 1974 she was readmitted to New York Hospital with severe pam m the left side of the chest She was afebrlle Physzcal examnat~on revealed a blood pressure of 112/74 mm Hg, a blue rmg of scleromalacla of the left eye, an early cataract of the right eye and a saddle nose (Fig 2), there was no deformity of the ears The erythrocyte sedlmentatlon rate was 38 mm m 1 hour, results of all other laboratory tests were normal Chest roentgenograms demonstrated a round mass, approximately 5 cm m diameter, at the aortlc arch and a poorly clrcumscrlbed density m the left upper lung An aortogram demonstrated a saccular aneurysm of the proximal descendmg thoraclc aorta that measured 5 cm m diameter (Fig 3A), and a fuslform aneurysm of the abdominal aorta below the renal arteries that measured 9 by 3 5 cm (Fig 38) The aortlc valve functioned normally, and the unmvolved aorta was normal m cahber and had a smooth lumen At operatzon, the saccular aneurysm commumcated with the aorta through a 1 by 2 cm elhpsold opening opposite the left subclavlan artery The aneurysm was incised and Its opening mto the aorta was patched with Dacron@, no aortlc tissue was removed The edge of the orlflce of the aneurysm felt thick and fibrotic, but the remainder of the vlsuabzed aorta appeared normal Biopsy of the radlographlcally demonstrated density m the left lung showed that it was a pulmonary infarct without evidence of pulmonary vasculltls After an uneventful postoperative recovery, the patient was discharged on a regimen of predmsone (25 mg/day), chloroqume (500 mg/day) and lsomazide (300 mg/day) In August 1974 she was readmitted because of contmuous lower abdominal pam that radiated to the back Retroperltoneal bleeding was found at operation, and the posterior wall of the abdominal aortlc aneurysm was necrotic and ulcerated The remainder of the abdominal aorta appeared normal A Dacron aortlc graft was successfully inserted, and to date her recovery has been uneventful
37
RELAPSING POLYCHONDRIT~S-CIPRIANO ET AL
FIGURE 3. Aortograms. A, thoracic aortogram in the left anterior oblique projection demonstrating a 5 cm saccular aneurysm in the proximal descending thoracic aorta. 6, abdominal aortogram demonstrating a 9 by 3.5 cm fusiform aneurysm of the abdominal aorta below the renal arteries.
FIGURE 4. Histologic sections of the abdominal aortic aneurysm. A, media demonstrating extensive loss and fragmentation of elastic fibers, deposition of collagen and mononuclear cell infiltrates. B, outer media demonstrating perivascular mononuclear cell infiltrates and dense collagenous scarring. C, scarred adventitia showing prominent mononuclear cell infiltrates adjacent to patent vasa vasorum. (Elastica-van Gieson (A) and hematoxylin-eosin stains; all X40, reduced by 46 percent .)
June 1976
The American Journal of CARDIOLOGY
Volume 37
1099
I
M
M
M
M
F
F
M
M
5
4
3
4
9
8
7
5
*
2
3
4
5
6
7
8
9
10
37
89
57
39
35
33
29
22
21
19
At Onset of RPC ______
38 2
92
573
48
36 7
39 7
44
23 7
25
19 2
+
+
+
+
+
_
+ _
+
+
_
+
_
__
+
+
+
_
_
_ _
+ _
+ _
f _
_
Dlastollc
systollc
Cardlomegaly ~~.___ +
Aortlc Valve Murmur
and Aortlc
_
_
0
?“A-V block 0
_
+
+
0
+
+ 1” and 2’ A-V block
0
+
-
1’ A-V block _
ECG
+
LV Failure
Aneurysms
Desc Th Ao and Lower Abd Ao
Asc Ao dlssectlon Desc Th Ao
Asc, Ao, arch and Desc Ao Desc Th Ao and upper Abd Ao
Asc Ao
Asc Ao and lower Abd Ao
Asc Ao and arch
Prox Asc Ao Lowe1 Abd Ao
site of Aneurysm ____ ~~
ears
Nose
Ears
Ears
ear, costochondrltls Ears, nose, trachea
Nose,
Nose,
Nose, ears, costochondrltls Nose, eats
Nose. ears
Nose, knees
Sttesof Chondrltts I_. __-
Eplsclerltls, retlnal detach ment,rheumatold arthrltls Eplsclerltls, scleromalacla, subcutaneous nodules, mlgratory arthralglas, cataract __--
tts
ConJunctlvl-
Eplsclerltls, muscle atrophy
Eplsclerms, migratory arthralglas Eplsclerltls
Eplscterltls, subcutaneous nodule, arthropathy, amputatlon of leg due to vasculltls Eplsclerltls, vertigo, deafness Serous otltls media, vertigo, eplsclerltls
Eplsclerltls
Associated Involvement ~_
dtd
CS, CLQ, Th and Abd Ao aneurysms repalred, doing well
CS, reportedly did well Aneurysm repaired, reportedly did well
CS, reportedly well
CS, 6MP. AVR, doing well 6 mo later CS. AZT. AVR, died 22 mo later of ruptured Abd Ao aneurysm CS, AVP, died suddenly 18 mo later CS, IMC, reportedly did well
CS, dted of LV failure CS, died of ruptured Abd Ao aneurysm
Treatment and ClInIcal Course __-___
+ = present, - = absent, 0 = data not available, Abd = abdoml?al, AO = aorta, Asc = ascending, AVP = Aoltlc valvuloplasty, AVR = aortlc valve replacement, A - V = atrIoventrlcular, AZT = azathloprlne, CLQ = chloroqulne, CS = cortlcosterold, Desc = descending, ECG = electrocardiogram, IMC = Indomethacln, LV = left ventricular, 6MP = 6 mercaptopurlne, mo = months, prox = proximal, RPC = relapsing polychondrltcs, Th = thoraclc
F
M
Sex __.~.
6
Reference
Aor t&c Aneurysm Detected
(yr)
Relapsmg Polychondrltls
Age
Features of Patients With _
1
CaSe “0
TABLE Clmlcal
RELAPSING
The media of the abdomuzal aortlc &sue removed atoperatlon was thinned and distorted by extensive loss and fragmentation of elastic fibers (Fig 4A) and deposltlon of collagen (Fig 4, A and B) The outer media showed increased vascularlzatlon and perlvascular mononuclear cell infiltrates (Fig 4B) The adventltla was densely scarred with collagen and it contained focal mononuclear cell infiltrates adjacent to patent vasa vasorum (Fig 4C) These hlstologlc findings are similar to those described In patients with relapsing polychondrltls and aortltls 3,4,10~11
Discussion The development of aortic aneurysms is a potentially fatal complication of relapsing polychondrltls, occurring in approximately 10 percent of patients,” and fatal rupture of clinically unsuspected aortic aneurysms has been found m this dlsease.3,5 Destruction of the media of the aorta, without aortlc dilatation, also has been reported m relapsing polychondritis lo,11
Histopathology: Relapsing polychondritls 1s characterized morphologically by inflammation of cartilage and by vascubtls localized to tissues with high concentrations of glycosammoglycans 3 Grossly, the aortic lesions appear to be focal, however, loss of all classes of glycosaminoglycans has been demonstrated histochemically throughout aortlc tissue that grossly and histologically appeared normal. The aortltis primarily mvolves the media, with increased vascularlzatlon, perlvascular mflltratlon of mononuclear cells, increased amounts of collagen and decreased amounts of elastic tissue and sulfated acid mucopolysaccharldes 4 The hlstopathologlc appearance of the aortic lesions m relapsing polychondrltls is distinct from that m Erdhelm’s cystic medial necrosis, Marfan’s syndrome, syphilitic aortltls and giant cell aortltls.4J’ The loss of glycosaminoglycans and the inflammatory reaction m the aorta have been considered secondary to the release of lysosomal enzymes from damaged cells 4 This concept has been supported by work showing that destructlon of cartilage and aortic media can be produced in rabbits by the intravenous mJectlon of crude papain 13Although the factors leading to cell damage m relapsing polychondritls remam unknown, It has been proposed that antlcartilage antlbodies,ni preclpitms against chondroitm sulfatel” and lymphocyte sensltlzatlon to chondromucoprotems15 are involved m the mechanism of the disease process Clinical features: Including our patient, 10 patients (7 men and 3 women aged 19 to 92 years, average 38 years) have been described as having aortlc aneurysms due to relapsing polychondrltls (Table I) J-g Aortlc disease became apparent from 3 months to 15 years (average 4.5 years) after the onset of symptoms of relapsing polychondritls, in five patients it was noted within 2 years Aortlc aneurysms developed most frequently m the ascending aorta (SIX patients: Cases 1,3, 4,5,6 and 8) Four of these SIX patients (Cases 1,3,5 and 6) were less than 40 years old when the aneurysms were detected. Three of the six patients with relapsing polychondritis and aneurysms of the ascending aorta also
POLYCHONDRITIS-CIPRIANO
ET
AL
had aneurysms of the abdominal aorta (Cases 1 and 2) or of the descending thoracic aorta (Case 6). All six patients with aneurysms of the ascending aorta had aortlc diastolic murmurs and left ventricular failure, five (Cases 1, 3, 4, 5 and 8) had cardlomegaly, and three (Cases 1, 4 and 8) had first or second degree atnoventrlcular block. None of these physical findings developed in the remaining four patients, who had mvolvement of the descending thoracic aorta (Case 9), the abdominal aorta (Case 2), or both (Cases 7 and lo), but not of the ascending aorta Thus, the cardiac clinical findings m patients with relapsing polychondrltls and aortlc aneurysms clearly differ depending upon whether or not the ascending aorta 1s involved The aortlc regurgitation is usually due to dilatation of the aortlc valve ring,3*4.11J6 alth ough thickening and retraction of the aortlc valve leaflets have been reported,” I7 and leads to left ventricular failure The conduction disturbances are probably due to extension of aortltls into the area of the bundle of His Treatment: Of the six patients with relapsing polychondritls and aneurysms of the ascending aorta, three (Cases 1, 6 and 8) were treated medically and three (Cases 3 to 5) underwent operation Of the three patients treated medically, one (Case 1) died of left ventricular failure and the other two (Cases 6 and 8) survived although Patient 8 had dissection of the ascending aorta. Two patients (Cases 3 and 4) underwent aortlc valve replacement, and the other (Case 5) had aortlc valvuloplasty Patient 4 died of rupture of a clinically unsuspected abdominal aortlc aneurysm 22 months after aortic valve replacement Patient 5 died suddenly of unknown cause 18 months after operation and Patient 3 was reported to be doing well 6 months after operation Of the four patients with relapsing polychondrltis and aneurysms not mvolvmg the ascending aorta, two (Cases 2 and 7) were treated medically. Patient 2 died of rupture of an abdominal aortlc aneurysm that had not been suspected clmically and Patient 7 had aneurysms m the descending thoraclc aorta and abdominal aorta and was reported to survive The other two of these four patients (Cases 9 and 10) survived surgical repair of aneurysms that involved the descending thoracic aorta m both and also the abdominal aorta m Case 10 Thus, four of the 10 patients with relapsing polychondrltls and aortlc aneurysms died. Two patients died of rupture of unsuspected aneurysms of the abdominal aorta, one of left ventricular failure and one of unknown cause No operative deaths or comphcatlons of surgery were reported The follouxng conclusions can be drawn from the data reuewed above (1) Aortic aneurysms are a relatively frequent complication of relapsing polychondntls; (2) these aneurysms occur most frequently m the as-
cending aorta but may be multiple and involve the abdominal aorta, (3) mvolvement of the ascending aorta results m aortlc regurgltatlon and left ventricular fallure; and (4) involvement of the abdominal adrta may be clmlcally silent and may result in fatal rupture
June 1976
The American Journal of CARDIOLOGY
Volume 37
1101
RELAPSING POLYCHONDRITIS-CIPRIANO
ET AL
Addendum In April 1975 the patient was readmitted to New York Hospital with sharp thoracolumbar pam of 4 days’ duration and a low grade fever A complete blood count was normal, but an erythrocyte sedimentation rate was 99 mm m 1 hour She had been taking predmsone (35 mg/day) before admission Thoracic and abdominal
aortlc arterlograms demonstrated the site of the patched thoraclc aortic aneurysm and a fusiform aneurysm of the abdommal aorta that began at the lower border of the abdommal aortic graft and involved both the left and the right common iliac arteries This new abdominal aortic aneurysm was repaired with a Y-shaped Dacron graft, without complication
References Pearson CM, Kkne HM, Newcomer VD Relapsrng polychondrrbs N Engl J Med 263 51-58, 1960 Dolan DL, Lemmon GB Jr, Teitelbaum SL: Relapsrng polychondrrtrs analytrcal literature revrew and studies on pathogenesrs Am J Med 41 285-299, 1966 Hughes RAC, Berry CL, Setfert M, et al: Relapsing polychondrrtrs three cases with a clrnrco-pathologrcal study and literature review 0 J Med 163 363-380, 1972 Pearson CM, Droening R, Verity MA, et al. Aorbc rnsuffrcrency and aor-bc aneurysm In relapsing polychondrrtrs Trans Assoc Am Physrcrans 80 71-90, 1967 Anderson B .Sr Ocular lessonsIn relapsrng polychondritrsand other rheumatord syndromes Am J Ophthalmol 64 35-50, 1967 Marquis Y, Rrchardson JB, Ritchre AC, et al. ldropathrc medial aortopathy and arteropathy Am J Med 44 939-954, 1968 Harner JW, Hamilton GW Aortrc abnormalities in relapsing polychondrrtrs report of a case wrth drssectrngaortrc aneurysm N Engl J Med 280 1166-l 168, 1969 Lang HD, Muller D, Ftnke J: Rezrdrvrerende Polychondrrtrs mrt Aortenaneurysrmen Dtsch Med Wochenschr 94 2033-2040, 1969 Owens DS Jr, lrby R, Toone EmRelapsng polychondrrtrswith aortrc involvement Arthritis Rheum 13 877-881, 1970
1102
June 1976
The American Journal of CARDIOLOGY
IO
11 12 13
14
15
16
17
Volume 37
Self J, Hammarsteln JF, Lyne B, et al: Relapsing polychondrrbs Arch Intern Med 120 109-112, 1967 Pappas G, Johnson M- Mitral and aot-bc valvular rnsuffrcrency In chronic relapsing polychondrrtrs Arch Surg 104 712-714, 1972 Hunder GG, Ward LE, Burbank MK: Grant cell arterrtrs producing an aortrc arch syndrome Ann Intern Med 66 578-582, 1967 Thomas L. Reversible collapse of rabbit ears after Intravenous papain, and prevention of recovery by cortrsone J Exp Med 104 245-252, 1956 Glynn LE, Holborow EJ: Conversion of trssue polysaccharides to auto-antigens by group A beta hemolytrc streptococcr Lancet 2 449-451.1952 Herman JH, Hess EV: lmmunopathologrc studres In relapsing polychondrrtrs (abstr 12 4) Abstracts of the VII European Rheumatology Congress, Brrghton, England, 1971 Yamazakt N, Garvata K, Hannya H, et al* A case of relapsing polychondrrtrs associated with aorbc tnsuffrciency Jap Heart J 7 188-195, 1966 Alexander CS, Derr RF, Sako Y. Abnormal ammo acrd composrtron of mitral and aortic valves replaced In a patient wrth chronrc relapsing polychrondrrtrs (abstr) Am J Cardrol 25 81, 1970
