Case Study: Giant Cell Arteritis with low ESR and CRP

Dillon Tinevez, MD – Anguilla Campus

Preceptor: DraganaRadovanovich, MD – Internist, University of Chicago,

Abstract

ESR and CRP are important lab markers that have been used to help support a diagnosis of giant cell arteritis (GCA). It has been reported that 7-20% of cases of GCA have a normal ESR. CRP is more sensitive and specific than ESR but when the tests are combined, the sensitivity increases to 99%.

This case study describes a 68-year-old female who presented with a right-sided headache and jaw claudication, and was found to have proximal muscle weakness and pain on palpation of the temporal area. The neurology team signed off of the case after a negative ESR (13.0 mm/hour) and negative CRP (1.1mg/dL) was found. Further investigation demonstrated wall thickening and mural enhancement of the right temporal artery on T1 post contrast imaging (MRA), and a temporal artery biopsy demonstrating areas of intimal thickening, luminal stenosis, and mononuclear infiltrate with necrosis, consistent with a diagnosis of GCA. High dose prednisone was started and the patients symptoms had subsided completely on 1 month follow up.

Although very rare, a diagnosis of GCA should not be excluded with ESR and CRP alone.

Keywords: giant cell arteritis, GCA, ESR, CRP, temporal artery biopsy, TAB, magnetic resonance imaging, angiography

Introduction

Giant Cell Arteritis is the most common form of vasculitis in adults and effects about 0.5-2.7 out of every 100,000 persons 50 years and older [1]. It is considered to be a neuro-opthalmic emergency and vision loss is the most significant form of morbidity [2]. It can also cause other life threatening complications like MI, stroke and aortic dissection [3]. The prognosis of GCA is very poor with up to 15% of patients experiencing vision loss [4].

The current workup for GCA includes initial labs with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which together have a sensitivity of 99% [5, 6]. Other laboratory findings can also prove useful, such as increased platelets, alkaline phosphatase, and AST. A normal CK, ANA, and RA may help eliminate some of the other differential diagnoses [7].

The gold standard for diagnosis is a superficial temporal artery biopsy (TAB) but this test is invasive and risky. A temporal artery duplex US is also very accurate at diagnosing GCA and other methods such as MRA and angiography have also proven useful [8].

GCA is thought to be an inflammatory response triggered by several factors such as genetics (increased rates in Northern Europeans), autoimmune factors (granulomatous histopathology), and environmental (C. Pneumonia, M. pneumonia), which all cause endothelial damage [9, 10]. The most common vessels affected are the temporal arteries but GCA can affect a wide variety of vessels, including the vertebral arteries, which explains the wide variety of symptoms associated with the disease.

ESR.This is a non-specific measure of inflammation in the body. It is increased in conditions like GCA, pregnancy, autoimmune conditions, anemia, some cancers (multiple myeloma, leukemia), etc. It is often decreased in conditions like polycythemia, hyperviscosity, congestive heart failure, and conditions with low plasma proteins (ie. renal failure). In most cases the ESR in GCA is at least 50mm/hr or higher but in 7 to 20% of cases, it is normal [5].

CRP.This is an acute phase protein that increases in blood plasma during inflammation. It is produced in response to macrophages and adipocytes releasing IL-6 during acute and chronic inflammatory conditions. CRP is more sensitive and specific for GCA but if you combine both of these tests together, the sensitivity rises to 99%.

A literature search of both PubMed and Google Scholar yielded a couple of studies that included TAB positive GCA with low ESR but the CRP was still elevated [11, 12]. Most of the studies and reviews done on this topic were investigating the utility of ESR and CRP in diagnosing GCA, which elucidated that CRP was more sensitive and specific than ESR in GCA. There is no mention of any cases of TAB positive GCA in which the ESR and CRP were both within normal range [13, 14].

Magnetic resonance imaging/angiography. Post contrast T1 images may demonstrate wall thickening and mural enhancement and the degree of enhancement is relative to the amount of inflammation. This can also be used to monitor treatment response. This modality is superior to CT imaging and Ultrasound [9].

Temporal artery biopsy. This is the gold standard for diagnosis and requires a biopsy of the temporal artery, thus making it fairly invasive. The pathologic hallmark for GCA is granulomatous inflammation of the internal elastic membrane of the media. Fragmentation of the internal elastic membrane, multinucleated giant cells, and mononuclear infiltrate are also pathological findings [9].

Case Report

A 68-year-old female presented to the emergency department complaining of a headache for two days. The headache was confined to the right temporal region and was worse on direct palpation of the area. The pain was 8/10, constant, did not radiate anywhere and had no alleviating factors, including Tylenol, which she was taking to try to help the pain. The headache was associated with jaw claudication when chewing food, fatigue, and many short episodes of blurry vision in both eyes that lasted less than twenty minutes for the last two days. She denied previous episodes, migraines, nausea/vomiting, dizziness, syncope, weakness, numbness, and photophobia. She has a past medical history of hypertension controlled with hydrochlorothiazide and amlodipine. She has never had any surgeries and has no known allergies. She admits to drinking casually, but denies smoking and recreational drugs. She lives at home with her boyfriend and has no children and had not travelled anywhere recently.

In the ED, the patient was started on 80mg prednisone, 1mg morphine, and IV fluids. Her EKG and CT head were both normal. The initial CBC showed platelets 421,000/UL, and hgb 11.2 but she says she has always been slightly anemic. BMP was within normal limits. UA and urine culture were negative. On physical exam, the patient had localized pain on palpation of the right temple, decreased visual acuity in both eyes (200/20 both OD/OS), and 3/5 proximal muscle weakness in the upper limbs bilaterally. She denied any pain, tenderness, and stiffness in her shoulders, back, and hips. The rest of her neurologic exam was normal.

The patient was admitted to the floor for a full neurologic workup and neurology was consulted. The neurology team originally suspected temporal arteritis but signed off after a negative ESR (13.0 mm/hour), a negative CRP (1.1mg/dL), and a normal neurologic physical exam. They concluded that the proximal muscle weakness was most likely due to another cause since there was no associated pain, tenderness, or stiffness making polymyalgia rheumatica (PMR), a condition known to be associated with half of all cases of GCA, less likely [15]. The patient refused to do a temporal artery biopsy initially so an MRA was done first. The MRA showed beading (wall thickening and mural enhancement) of the right temporal artery on T1 post contrast imaging, which is highly suggestive of temporal arteritis. After the positive MRA, the patient agreed to a right superficial temporal artery biopsy. The biopsy showed areas of intimal thickening, luminal stenosis, and mononuclear infiltrate with necrosis, consistent with a diagnosis of GCA. The patient was continued on prednisone and referred to a neuro-opthalmologist. Follow up 1 month later found no recurring symptoms. Subsequent long-term follow up was not done.

Discussion

As mentioned earlier, GCA is a neuro-opthalmic emergency with a poor prognosis and very serious outcomes, like stroke and blindness. It can often be missed because the presenting symptoms vary so widely. In this case the patient had labs inconsistent with most cases of GCA (low ESR and CRP), which prompted the neurology team to sign off and disregard the case. If it wasn’t for the strong clinical suspicion of the medicine team and a subsequent workup (MRA and TBA) the patient may have suffered severe complications from the disease. Being the most common form of vasculitis in adults, it is important to be aware of unconventional cases like this one. There are also reports of rare cases in which the disease predominately affects other vessels in the body such as the internal carotid arteries or the vertebral arteries. These cases can present with uncommon symptoms, such as progressive side-alternation deficits and may be difficult to diagnose [16].

Our literature search did not reveal any other case that had TAB positive GCA with normal range ESR and CRP Again, most cases of GCA have ESR at least 50mm/hr or higher, however 7 to 20% of cases have a ESR within normal range. In some cases this may be a result of concurrent medications or disease processes that can lower ESR but our patient was not using any medications and had no other known disease processes that are known to effect ESR. CRP isn’t always reported in cases but it has been shown to be more sensitive and specific than ESR with a combined sensitivity of 99%. Even given this high sensitivity, a diagnosis of GCA should not be excluded with ESR and CRP alone as shown in our case.

Some of the findings that prompted further investigation despite negative labs were the patients age (>50) and female gender (females are twice as likely to get GCA than males) [15, 17, 18]. The point tenderness that was found in the right temporal region above the temporal artery is often found in GCA affecting the temporal arteries. Proximal muscle weakness found in the upper extremities or hips can sometimes be associated with PMR. As mentioned earlier, PMR is found in roughly 50% of all cases of GCA and is a syndrome of stiffness and pain usually found in the arms and shoulders but can be found anywhere in the body. Isolated weakness with no pain or tenderness, especially in the mornings, is not consistent with PMR prompting the neurology team to deem this physical finding insignificant [15].

Conclusion

We reported a case of TAB positive GCA with normal ESR and CRP, which was not found in our literature search. ESR may be normal in 7-20% of cases but the sensitivity of combined ESR and CRP is 99%. Even though the sensitivity is very high for these combined tests, a diagnosis of GCA should never be excluded with these lab variables alone.

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