Abstract
Introduction: Calciphylaxis is a condition that causes vascular calcification and intimal proliferation with thrombotic occlusion of small-to-medium-sized vessels. Case Presentation: We describe a case of a 64-year-old woman who presented with a clinical picture that was suggestive of anterior arteritic ischemic optic neuropathy due to giant cell arteritis (GCA), but was found to have calciphylaxis confirmed by histologic examination. When calciphylaxis affects the blood supply to the eye, commonly it causes sudden vision loss, pallid optic disk edema, and a relative afferent pupillary defect, all of which were observed in our patient. Conclusion: There is no known cure for calciphylaxis, while in GCA, high-dose corticosteroid therapy is essential to prevent involvement of the contralateral eye. As the management approaches for these two diseases are different, it is important to have performed a thorough clinical examination along with detailed histopathological testing to rule out calciphylaxis of the temporal artery in patients suspected to have GCA.
Introduction
Calciphylaxis is a rare pathophysiological condition that causes arterial calcification. It occurs commonly in patients with end-stage renal disease but can also affect patients without renal failure [1]. Skin manifestations are the most common presentation; however, vascular calcifications can also occur in other organs such as the eyes, brain, intestines, mesentery, lungs, and skeletal muscles [2]. As described in previous case reports, calciphylaxis of the temporal artery usually is present in a manner similar to giant cell arteritis (GCA). Our case report provides further support for this observation in which biopsy was the differentiating hallmark.
Case Report
A 64-year-old woman, with a medical history of hypertension, diabetes, and ischemic heart disease, who had undergone percutaneous coronary intervention and was on aspirin and enoxaparin was referred to our institute due to a sudden vision loss in her left eye. The vision loss was abrupt, and onset was a week prior to presentation as a central scotoma, which progressed the next day to a generalized visual decline, with hand motion (HM) vision. It was associated with a bilateral temporal new onset headache more on the left side, occasional jaw claudication, fatigue, and decreased appetite, but no history of pain while combing her hair, fever, weight loss, peripheral numbness, or weakness. She had no history of kidney disease or renal hemodialysis. The patient had undergone phacoemulsification and intraocular lens implantation of the left eye 8 months prior to presentation with good postoperative vision. Prior to referral, a contrast high-resolution cranial magnetic resonance imaging was performed at the primary hospital that reported no optic nerve enhancement or cerebral calcifications (see Fig. 1).
On presentation, the temporal artery was palpable with tenderness, and no pulsation was detected. Visual acuity was 20/60 in the right eye (OD) and HM in the left eye (OS). Examination of the right eye showed a nuclear sclerotic cataract and a healthy disk with a cup-to-disk ratio of 0.5, while the left eye showed an afferent pupillary defect, a swollen optic disk, and superior and inferior disk pallor with some splinter hemorrhages (see Fig. 2). The clinical picture was suggestive of anterior arteritic ischemic optic neuropathy due to GCA, and the patient was admitted for investigation and management. The erythrocyte sedimentation rate (ESR) was high at 48 mm/h (upper limit of normal based on our patient’s age and sex: 64 + 10/2 = 37 mm/h), whereas C-reactive protein (CRP) and platelet counts were within normal limits. Urea, creatinine, bilirubin, calcium, and phosphorus levels were all within normal ranges. The patient received intravenous methylprednisolone (1 g) for 3 days during admission and was then switched to oral steroids (70 mg daily). A left temporal artery biopsy was performed 5 days after the patient’s presentation, which showed a thickened tunica intima with focal calcifications and no inflammation in the vascular wall suggestive of vasculitis. The patient was discharged with oral steroid treatment.
One month later, the patient presented with improved visual acuity in both eyes of 20/50 OD and 1/200 OS. Color vision was 15/15 OD and 0/15 OS. The patient still had a left afferent pupillary defect, and the optic disk became pale in the left eye. CRP level was elevated during this visit. The steroid dose was reduced to 60 mg daily, and the patient continued tapering the dose to 30 mg with no worsening of symptoms.
Four months after the initial presentation, the patient experienced episodes of recurrent painful itchy skin rashes. The rashes improved with increasing steroid doses and worsened with steroid tapering. Upon examination, the rash was highly suggestive of cutaneous vasculitis. Autoimmune profiles, including antinuclear antibodies, central antineutrophil cytoplasmic antibodies, perinuclear antineutrophil cytoplasmic antibodies, anti-Sjögren’s syndrome A, anti-Sjögren’s syndrome B, rheumatoid factor, and cryoglobulin along with the hepatitis serology, were all negative. A skin biopsy performed at another facility revealed extensive psoriasis that did not respond to ultraviolet light A. The patient was started on subcutaneous methotrexate 15 mg weekly, and prednisolone acetate was tapered to 25 mg daily.
The patient was in her usual state of health until she experienced another sudden decrease in vision 2 years after the initial episode, which affected the right eye, with other GCA symptoms. She underwent laboratory testing elsewhere which revealed an elevated ESR of 56 mm/h and was started on 60 mg steroids. She then visited our institute’s emergency room with a visual acuity of counting fingers OD, 1/200 OS, and bilateral pale optic disks with pallid swelling OD. The Goldman visual field test revealed depressed and constricted fields bilaterally (see Fig. 3). Her steroid dose was increased to 70 mg with no improvement, and she returned to the emergency room 2 weeks later with a visual acuity of HM OD and 1/200 OS. The patient underwent another superficial temporal artery biopsy on the right side. The histologic examination revealed serial sections in the medium-sized artery with similar findings to her first temporal biopsy, which showed focal calcifications confined to the tunica media, confirming the diagnosis of calciphylaxis. No inflammation was observed, thus excluding giant arteritis (see Fig. 4).
Discussion
Calciphylaxis, or calcific uremic arteriolopathy, is a condition that causes vascular calcification and intimal proliferation of small-to-medium-sized vessels in 0.04 to 4% of patients having end-stage renal disease. Thrombotic occlusion of the affected vessels leads to painful ulcerative skin lesions; however, the eye, brain, intestines, mesentery, lungs, and skeletal muscles may also be affected. When the eye is affected, calciphylaxis commonly causes sudden vision loss, pallid optic disk edema, and a relative afferent pupillary defect, all of which were observed in our patient [1, 3]. Additionally, the presence of skin manifestations following the initial loss of vision drives the diagnosis toward calciphylaxis. Although the histopathological diagnosis was psoriasis, which is not a classical ulcerative skin lesion characteristic of calciphylaxis, four previous calciphylaxis cases have been reported in patients with psoriasis, indicating that psoriasis might be a stimulus for calciphylaxis [4‒7].
Risk factors include increased serum phosphate, calcium phosphate products, and parathyroid hormone levels [8]. Although it mostly affects patients with renal disease, nonuremic calciphylaxis is a subtype that affects patients with no history of kidney involvement or hemodialysis. Other risks of nonuremic calciphylaxis include malignant neoplasm, alcoholic liver disease, autoimmune disorders, and corticosteroid use, all of which were unknown to our patient [9].
No known cure has been found for calciphylaxis; however, the main approach consists of managing renal disease and maintaining low calcium and phosphate levels with regular hemodialysis or possibly a kidney transplant. Intravenous sodium thiosulfate decreases soft tissue calcification and has been proven to enhance skin lesions and decrease the mortality rate in patients with calciphylaxis without visual improvement. In contrast to GCA, corticosteroid use showed no benefit and may even worsen calciphylaxis. Along with poor therapeutic response, calciphylaxis is associated with poor prognosis. The 1-year mortality rate is 45–80%, mostly due to infected ulcerated skin lesions [1, 3].
GCA is an inflammatory vasculitis that involves the medium- and large-sized arteries and mostly the temporal arteries. When the ophthalmic or posterior ciliary arteries are involved, permanent visual loss occurs due to ischemic optic neuropathy. Once this occurs, starting high-dose corticosteroids is essential to prevent involvement of the contralateral eye. Occasionally, oculomotor nerve palsy occurs because of ischemia, leading to diplopia, which generally manifests before vision loss [10].
The disease mostly affects older individuals, above 50 years of age, and females as in our case. Fever, fatigue, malaise, weight loss, anorexia, headache (usually temporal), scalp tenderness, jaw claudication, and temporal artery abnormalities, such as tenderness, pulselessness, enlargement, or nodular swelling, are all signs and symptoms of GCA. Studies documenting examination of patients with vision loss resulting from GCA reported a pale edematous optic disk during the acute stage, which changed to optic atrophy in the chronic stage. Acute phase reactants, including ESR and CRP, are usually elevated but are not sufficient for diagnosing GCA, as a temporal artery biopsy is the gold standard, revealing inflammatory infiltrates of the vessels with a sensitivity of 77%. Although temporal artery biopsy is essential for diagnosing GCA, steroids should be administered immediately to decrease the risk of visual loss in the other eye. After starting steroid therapy, a biopsy should be performed in the first 2 weeks to maintain a high yield [10].
According to the 2022 American College of Rheumatology/EULAR classification criteria for GCA, our patient met the criteria for diagnosing GCA, as 6 is the minimum score required for making a diagnosis, and she fulfilled a cumulative score of 14. She had sudden loss of vision (+3), CRP greater than 10 mg/L (+3), new temporal headache (+2), jaw claudication (+2), scalp tenderness (+2), and abnormal temporal artery (+2) [11]. Although our patient had beyond the required score for GCA diagnosis, she was diagnosed with calciphylaxis rather than GCA based on biopsy results. This may explain the recurrence of symptoms with contralateral involvement, although the patient was on immunosuppressants, including methotrexate, which has a debatable role in GCA. To preserve the remaining vision in our patient and prevent the involvement of other organs, a management regimen for calciphylaxis should be initiated.
Previous case reports have described similar presentations of calciphylaxis of the temporal artery mimicking GCA in patients with and without renal disease. These cases had temporal artery biopsies with results showing calcification of the temporal arteries with no inflammation, thus excluding GCA. Reported cases were given either steroids or sodium thiosulfate with no improved outcomes in both groups [3]. The management approaches for these two diseases are different, which makes it important to perform a thorough clinical examination along with detailed histopathological testing to rule out calciphylaxis of the temporal artery. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000541410).
Statement of Ethics
The study obtained ethical Approval No. 23003 by the King Khaled Eye Specialist Hospital Institutional Review Board. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.
Conflict of Interest Statement
The authors have no conflicts of interest to declare.
Funding Sources
This study was not supported by any sponsor or funder.
Author Contributions
W.A. and N.A.: conceptualization and writing – original draft, review, and editing. A.M.: conceptualization and writing – reviewing and editing.
Data Availability Statement
All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.