Keywords coronary artery disease - Immunoglobulin G4-related disease - rapidly progressive coronary stenosis
Introduction
Immunoglobulin G4-related disease (IgG4 RD) is an autoimmune condition associated with increased level of IgG4 in the plasma. The first case described was of autoimmune pancreatitis.[1 ] Coronary involvement, albeit rare, is important in IgG4 RD, since it causes coronary stenosis presenting as acute coronary syndrome or coronary aneurysm rupture.[2 ] We present a patient of IgG4 RD with coronary vasculitis being the sole manifestation.
Case Presentation
A 61-year-old lady, with no known comorbidities, presented with recurrent attacks of palpitation for 6 months along with an acute single episode of atypical chest discomfort for last 6 hours. Electrocardiogram showed ST-segment depression in the inferior wall leads along with elevated troponin T (0.76 ng/mL) and pro-B-type natriuretic peptide (3160 pg/mL). In view of provisional diagnosis of non-ST-elevation myocardial infarction (NSTEMI), catheter angiogram was done which revealed no significant coronary disease ([Fig. 1 ]). She was discharged on antiplatelets, statins, beta-blockers, and nitroglycerin.
Fig. 1 Normal opacification of left anterior descending (LAD), left circumflex (LCx; A ), and the right coronary artery (RCA; B ). No obvious stenosis or occlusion seen.
However, 3 months later, she again presented with NSTEMI. Angiogram this time revealed significant diffuse narrowing of all three coronaries. To evaluate any underlying cause of this rapidly progressive disease, computed tomography coronary angiography (CTCA) was planned. CTCA revealed diffuse wall thickening with adjacent fat stranding along all three coronaries—suggestive of coronary periarteritis ([Fig. 2 ]). No aneurysm or ectasia was seen. Erythrocyte sedimentation rate was elevated (86 mm/hr), C-reactive protein was positive. Vasculitis workup was negative, although serum IgG4 level was elevated (1.59 gm/L). Coronary artery bypass grafting was not feasible as distal vessels were poorly graftable and left anterior descending stenting was not done in view of on-going coronary inflammation and high risk of stent thrombosis.
Fig. 2 Periarterial soft tissue thickening (arrows) along the left anterior descending (LAD) (A ), left circumflex (LCx) (B ), and right coronary artery (RCA) (C ) causing significant stenosis of all three coronaries.
Positron emission tomography showed tracer uptake along the walls of the infrarenal aorta, around bilateral common iliac arteries and the femoral arteries ([Fig. 3 ]). Patient was started on prednisolone and azathioprine. Follow-up CT after 3 months of steroid showed resolution of wall thickening around the right coronary artery (RCA) ([Fig. 4 ]) and fall in the serum IgG4 levels to 1.1 gm/L. There was minimal resolution of pericoronary wall thickening of the left-sided coronaries. The patient has been kept on close medical management with dose adjustments of steroids and immunomodulators and has been doing fine for the last 2 years.
Fig. 3 Increased positron emission tomography (PET) tracer uptake along the anterior wall of the infrarenal abdominal aorta.
Fig. 4 Significant reduction of soft tissue (arrow) along the right coronary artery (RCA) posttreatment with steroids.
Discussion
IgG4 RD is an enigmatic disease, first described in 2001 in Japan.[1 ] The 2020 revised comprehensive diagnostic by Umehara et al is useful in diagnosis.[3 ] Diagnostic criteria includes clinical and radiological, serological, and histopathological features. Histopathological confirmation is often difficult to achieve, and fulfilling of clinical/radiological and serological items satisfies the criteria of “possible diagnosis.” It usually involves the salivary glands, pancreas, thyroid, retroperitoneum, and orbits. Coronary involvement as a manifestation of IgG4 RD is rare and we could find 16 cases reported in the literature ([Table 1 ]). A review of these cases revealed male-to-female ratio of 15:1, with only one case being a female. This is contrary to the general belief of autoimmune disease being more prevalent in females.
Table 1
Summarizing coronary involvement of IgG4 related disease, reported previously in the literature
Reported case
Age
Sex
Coronary artery features
ACS
Coronary involved
Any other system involved
Treatment
Nishimura et al[4 ]
60
M
Stenosis and aneurysm.
No soft tissue thickening
No
RCA and LAD.
CNS - recurrent MCA Strokes
Steroids
Tanigawaet al[5 ]
66
M
Periarterial thickening and subtotal occlusion
AMI
RCA and LCx
No
CABG
Bito et al[6 ]
69
M
Aneurysm, no stenosis or soft tissue
AMI
RCA and LMCA-LAD
No, past H/O lymphoma
Steroids f/b CABG
Matsumo et al[7 ]
60
F
Pericoronary pseudotumor, no stenosis or aneurysm
No
RCA
IRAAA
CABG and surgical repair of AAA
Ikutomi et al[8 ]
75
M
Stenosis, ectasia, and pericoronary soft tissue
Angina
Stenosis of LAD, LCx, ectatic RCA, soft tissue around all
Pancreas and parotid
CABG and steroids
Tajima et al[9 ]
68
M
Pericoronary soft tissue thickening and multiple aneurysms
No
Not mentioned
Multiple large and medium vessel aneurysm, parotitis
Low dose steroids—lead to ruptured splenic aneurysm and death
Inokuchi et al[10 ]
38
M
Stenosis and occlusion
Yes - SCD
RCA and LAD
Not known
Postmortem dx
Urabe et al[11 ]
84
M
Aneurysm and wall thickening
Yes
All 3
Celiac, renal arteries, DTA, and AA
Steroids - tapering lead to sudden death due to ruptured DTA aneurysm
Patel et al[12 ]
53
M
Severe stenosis with wall thickening
Yes - SCD
TVD
Kidney, pancreas, retroperitoneum, and mediastinal nodes
Postmortem study
Guo et al[13 ]
88
M
Periarterial soft tissue thickening
No
All 3 coronaries
Nasal cavities, maxillary sinus, orbits, nodes, IRAAA, lung involvement
Steroids
Takei et al[14 ]
71
M
Aneurysms and stenosis
No
TVD
Salivary glands, biliary system, respiratory tract, IRAAA
Steroids and cyclophosphamide
Keraliya et al[15 ]
53
M
Aneurysms, wall thickening, and stenosis
Yes
LMCA - proximal LAD, RCA
AAA and SMA aneurysm
CABG
Sakamoto et al[16 ]
67
M
Soft tissue thickening and stenosis
No
LAD and RCA
Pancreatitis
Steroids
Komiya et al[17 ]
59
M
Soft tissue thickening
No
RCA and LAD
Submandibular sialadenitis, IRAAA
Steroids
Kan-o et al [18 ]
68
M
Aneurysm, wall thickening
No
RCA and LAD
IRAAA, chronic pancreatitis,
nephritis
Steroids and surgical treatment of IRAAA
Okuyama et al[19 ]
74
M
Occlusion and wall thickening
Yes
RCA and LAD
Pancreatitis
PCI to LAD
Abbreviations: AA, aortic aneurysm; AAA, abdominal aortic aneurysm; ACS, acute coronary syndrome; AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; CNS, central nervous system; DTA, descending thoracic aorta; dx, diagnosis; F, female; f/b, followed by; H/O, history of; IRAAA, infrarenal abdominal aortic aneurysm; LAD, left anterior descending; LCx, left circumflex; LMCA, left main coronary artery; M, male; MCA, middle cerebral artery; PCI, percutaneous coronary intervention; RCA, right coronary artery; SCD, sudden cardiac death; SMA, superior mesenteric artery; TVD, triple vessel disease.
The primary findings in our case were rapidly progressive diffuse triple vessel stenosis and pericoronary wall thickening. Differentials considered can be Takayasu arteritis (TA), giant cell temporal arteritis (GCTA), polyarteritis nodosa (PAN), cytoplasmic antineutrophil cytoplasmic antibody (c-ANCA)-associated vasculitis, Behcet's disease (BD), IgG4 RD, and Erdheim–Chester disease (ECD).[20 ] Our case had no large or medium artery involvement, no renal artery stenosis, no complaints of any headache or jaw claudication, or no hypertension, thus virtually ruling out TA and GCTA.[21 ] c-ANCA and perinuclear ANCA both were negative, there was no medium-sized vessel aneurysm, no renal function abnormality, no hematuria, and no history or any genital, oral, or ocular ulcer—thus excluding PAN, Wegener's disease, and BD.[22 ] IgG4 RD and ECD—both are rare conditions—can have considerable overlap in their clinical-radiological features with biopsy being the definitive way of differentiating between the two.[23 ] However, bone involvement is almost seen in around 95% of cases of ECD, which was absent in our case. Thus, excluding other causes, presence of IgG4 in the serum and response to treatment lead us to a provisional diagnosis of IgG4 RD.
Coronary involvement in IgG4 RD mainly has three forms—stenosis, aneurysm, and pericoronary soft tissue thickening. Of the 16 cases reported in literature, 12 had coronary involvement in the form of wall thickening. Coronary stenosis was seen in 8 cases and coronary aneurysms were seen in 7 cases. Coronary aneurysms are associated with high risk of rupture and mortality and thus warrant high-dose prednisolone and/or surgical therapy. Of the coronaries, proximal RCA involvement was seen in 100% of the cases, thus it may be a specific feature in IgG4 RD. Involvement of the proximal coronaries were more commonly seen. Isolated distal coronary arterial involvement was not seen.
For confirmation of diagnosis, tissue biopsy is the gold standard. But in isolated coronary involvement with sparing of the glands or any other accessible sites, biopsy is difficult. Thus, radiology with clinical history and serology becomes diagnostically important.
Conclusion
Pericoronary wall thickening, stenosis, and aneurysms in the elderly with absence of risk factors of atherosclerosis with rapid progression of stenosis should point toward IgG4 RD. The entity should be kept in the differential since management is different from atherosclerosis and the condition responds favorably from immunosuppression.
