A Case of Complete Heart Block Secondary to ANCA-Associated Vasculitis
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A Case of Complete Heart Block Secondary to ANCA-Associated Vasculitis
in Tro Duc Tion Anti - neutrophil cy toplasmic antibody ( ANC A ) associated vasculitides are systemic autoimmune diseases that often present as non-specific prodromal symptoms such as fever, fatigue, headache, and weight loss.1 With modern treatment, the disease has changed from being universally fatal to being treatable. It can have a chronic relapsing and remitting course. Therefore, early diagnosis is necessary.2,3
ca SE Pr ESEn TaTion
A 53-year-old male with a past medical history of
chronic sinusitis and some epistaxis needing multiple
courses of antibiotics and steroids, was admitted after
being diagnosed with high-grade heart block at another
institution. He was found to have a heart rate of 26 and
was given a temporary pacemaker prior to the transfer.
Subsequently, a dual-chamber pacemaker was placed.
An echocardiogram showed mild aortic stenosis and
regurgitation with right ventricular enlargement and an
ejection fraction of 65%. No etiology was found for the
heart block and work up was negative for medications,
electrolytes, ischemia, significant structural heart disease
or lyme disease. Pacer placement was without any
complications. The patient was discharged home and
did well for 10 days and then returned again to the
emergency room with complaints of dry cough, chest
pain, progressive shortness of breath, fatigue, and fever
to 101.2 degrees Fahrenheit. He reported a fifteen pound
weight loss over the past month. His family history was
noncontributory. He worked as an auto mechanic and
reported former cocaine use over 20 years ago. He had
no history of tuberculosis exposure and was up to date
on his screening colonoscopy.
Physical exam findings included mildly congested
bilateral nares with some postnasal thick secretions.
On careful examination, he had “saddle nose” anatomy
that he claimed to have noticed just months prior to
presentation. Auscultation of his lungs revealed crackles
diffusely and posterior left lung base egophony but no
wheezes. The lung findings were new as compared to
the recent admission for heart block. There was nothing
significant on the basic laboratory tests. Chest x-ray and
CT scan on admission revealed diffuse bilateral airspace
opacities and nodule consolidation with mediastinal and
right hilar adenopathy. These findings were suspicious
for multifocal pneumonia with a separate infectious
DiFFEr En Tial Diagno SiS
On initial presentation the differential diagnosis ranged
from infectious to autoimmune to malignant pathology.
There was initial concern for tuberculosis, pneumonia
Ho SPiTal c our SE
Blood, urine and sputum cultures didn’t identify any
bacterial or fungal infectious etiology. AFB stains
were negative. He underwent bronchoscopy to better
evaluate the lung process and biopsy was performed
revealing mild interstitial pneumonitis and intraalveolar
red blood cells. Further in the course, patient developed
acute kidney injury with a baseline creatinine of 0.9 mg/
dl that peaked at 2.0 mg/dl. He had no evidence of
oliguria or dysuria. Based on his constellation of signs
and symptoms, he underwent a work-up for vasculitides.
This included pertinent negatives for the following lab
studies: HIV screening, hepatitis serologies, anti-nuclear
antibody (ANA), double stranded DNA (dsDNA), reduced
complement levels, basement membrane antibody,
anti-Ro/anti-La antibodies, and quantiferon assay.
ANCA screen came back positive for p-ANCA
(antimyeloperoxidase). A kidney biopsy revealed interstitial
granulomatous inflammation with pauci-immune
staining that was consistent with p-ANCA related
glomerulonephritis. He was started on high-dose pulse
steroids and cyclophosphamide.
This patient’s prodromal flu-like symptoms of fever,
fatigue, and weight loss were classic for the initial
vasculitis presentation.1,4 His history of chronic sinusitis
and epistaxis that was best relieved by steroids was
also an indication of vasculitic disease.5 The lung
biopsy showing hemorrhagic alveolar infiltrate and
kidney biopsy showing glomerulonephritis were
most consistent with granulomatosis with polyangiitis
(GPA). However, no granulomatous vasculitis or
pulmonary capillaritis were seen in his lung biopsy.
Large observational studies have shown that rhinology,
pulmonary, and renal are the systems most commonly
affected in this spectrum of diseases.6 This patient
presented with heart block prior to the typical vasculitic
symptoms. As no clear cut etiology was found for his
heat block, there was a high suspicion for vasculitic
origin of his heart block. On our review of literature, we
found small number of case reports that reported first
degree to complete heart block in patient’s with GPA
and other vasculitides.
ANCA-associated vasculitis is a subset of small-vessel
vasculitis and includes GPA, eosinophilic granulomatosis
with polyangiitis (EPGA), and microscopic polyangiitis
(MPA). It is usually found in older adults but is reported
in all ages.5 GPA specifically shows granulomatous
inflammation of the respiratory tract and abnormal urinary
sediment. MPA shows no granuloma formation. EPGA
shows characteristic rhinitis, asthma, and eosinophilia.7
Cardiac complications of GPA are thought to be rare.
While involvement of heart has been reported to be
around 30% at autopsy in known GPA, clinical cardiac
involvement is low.8 A recent report indicated evidence
of cardiac involvement in 8% to 16% at the time of
diagnosis and upto 25% during the course of the disease.
9 The predominant cardiological involvement has been
pericarditis (effusion), coronary arteritis and myocarditis
(left ventricular dysfunction) on pathology.10 Valvuvar
and conduction defects have been rarely described
in the past. More recently, there have been increasing
number of reports of conduction disease defects as well
as valvular abnormalities associated with GPA. GPA can
have pathological involvement of aortic or mitral valve,
54 | The Medicine Forum
causing valvulitis leading to regurgitation as predominant
valve dysfunction.9 GPA has also been associated with
bundle branch blocks to all grades of heart block. These
are thought to be from granulomatous inflammation
involving the AV node or the bundle of his.11 We believe
that our patient’s heart block was associated with GPA.
The close time between the two diagnosis, as well as
similar sequence of events like diagnosis of heart block
first and then diagnosis of GPA in some other case
reports substantiate our association. Heart block has
been reversible with treatment of GPA with
immunosuppression in some literature.12-14
The approach to treatment of ANCA associated vasculitis
can be divided into two categories: mild disease and
moderate to severe disease. For mild disease, with no
evidence of glomerulonephritis or organ-threatening
disease, a regimen of glucocorticoids in combination
with rituximab or methotrexate should be started. If
the disease is refractory to methotrexate treatment
the patient should have a trial of cyclophosphamide.
Moderate to severe disease demonstrates organ damage
and has a less defined recommendation for treatment.
Overall, literature supports either a cyclophosphamide or
rituximab-based regimen in combination with
glucocorticoids.3 Prophylaxis against opportunistic infections
during induction immunosuppression is also suggested.
Our patient's heart block resolved before starting steroids,
so it was likely a temporary block.
KEy Poin TS
ANCA-associated vasculitis can initially present with
prodromal flu-like symptoms and signs of inflammation.
Thought not very common, ANCA-associated vasculitis
can be associated with cardiac valvulopathy and
conduction abnormalities. Patients presenting with
heart block and recent history of or current symptoms
of inflammatory or infectious disease, should be
screened for GPA and vasculitides in addition to lyme
disease and viral myocarditis work up. If caught early,
heart block due to vasculitis is potentially reversible
and can save a patient from unnecessary procedures.
The management consists of immunosuppression with
steroids and other agents.
r EFEr Enc ES
"Sunset at the Jersey Shore”
photograph by Michael Valentino, MD, PhD
1. Watts R , Lane S , Hanslik T , Hauser T , Hellmich B , Koldingsnes W , et al. Development and validation of a consensus methodology for the classification of the ANCA-associated vasculitides and polyarteritis nodosa for epidemiological studies . Ann Rheum Dis . 2007 Feb; 66 ( 2 ): 222 - 7 .
2. Falk RJ , Hogan S , Carey TS , Jennette JC. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. the glomerular disease collaborative network . Ann Intern Med . 1990 Nov 1 ; 113 ( 9 ): 656 - 63 .
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10. Fauci AS , Haynes BF , Katz P , Wolff SM . Wegener's granulomatosis: Prospective clinical and therapeutic experience with 85 patients for 21 years . Ann Intern Med . 1983 Jan; 98 ( 1 ): 76 - 85 .
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14. Reinhard W , Kallmuenzer B , Bergua A , Fleck M , Luchner A , Riegger G , et al. Reversible complete heart block in ANCA-associated vasculitis . Clin Res Cardiol . 2011 Jan; 100 ( 1 ): 93 - 5 .