Angiographic imaging of the testicular arteries with polyarteritis nodosa: A case report

Abstract

Polyarteritis nodosa (PAN) is a form of vasculitis characterized by necrotizing arteritis of medium or small arteries, and can involve any organ. Frequently, it affects multiple organs, but may sometimes be localized to single area such as the testes. Angiography can be a diagnostic alternative to tissue biopsy and surgery. Some previous studies have reported that presented the angiographic evidence of the involvement of the renal, hepatic, splenic, superior mesenteric, inferior mesenteric, and extremity arteries in PAN, but there are apparently no past reports of the involvement of the testicular arteries. We herein present angiographic findings of testicular artery involvement in PAN.

Introduction

Polyarteritis nodosa (PAN) is a form of vasculitis characterized by necrotizing arteritis of medium or small arteries, and can involve any organ [1]. Frequently it affects multiple organs, but may sometimes be localized to single area such as the testes [2]. PAN is diagnosed by its clinical features and pathological and/or angiographic findings [1,3]. Angiography can be a diagnostic alternative to a tissue biopsy and surgery. Previous studies have reported that angiographic evidence of the involvement of the renal, hepatic, splenic, superior mesenteric, inferior mesenteric, and extremity arteries in PAN [[4], [5], [6]], but there are apparently no angiographic findings of testicular artery involvement. We herein present angiographic findings of testicular artery involvement in PAN. Angiography may be useful especially in diagnosing PAN localized in the testes, which initially presents with orchitis or epididymitis.

Case presentation

A male patient in his 70s presented with impaired consciousness and mild motor impairment of about 1 month's duration. He had type 2 diabetes mellitus under poor glycemic control.

A physical examination revealed fever higher than 100 degrees Fahrenheit), weight loss, left thigh myalgia, left iliopsoas and quadriceps muscle weakness, abdominal, thigh, and knee livedo or cutaneous nodules, and bilateral testicular pain. Laboratory tests found significant inflammation, including white blood cells 13,600 /μL (reference range: 3300-8600/μL) (neutrophils 88%, lymphocytes 5%, monocytes 5%, eosinophils 2%, basophils 0%), a C-reactive protein 36.22 mg/dL (reference range: < 0.14 mg/dL), and erythrocyte sedimentation rate 103 mm / 1 hour (reference range: 2-10 mm/1 hour). His blood glucose was elevated to 244 mg/dL (reference range: 73-109 mg/dL) due to the poorly controlled diabetes mellites. Platelets, blood urea nitrogen, creatinine and other laboratory data were almost normal. Serologically, MPO-ANCA and PR-3 ANCA were negative, as were Hepatitis B surface antigen and other viral antigens. Ultrasonography detected a hydrocele in the left testicle, but found no infarction or hematoma.

Computed tomography (CT) of the head and the whole body and magnetic resonance imaging (MRI) the head were performed to exclude malignancies and to investigate the source of inflammation. CT and MRI demonstrated no malignant tumors, focus of infection, or the intracranial disease. CT demonstrated arterial ectasia, wall thickening, and enhancement of the bilateral testicular arteries, notably near the testes (Figs. 1A and B).

Fig. 1.

CT at PAN onset. CT axial image of the arterial phase at the level of the spermatic cords (A) and CT angiography (B). Testicular artery ectasia CT image of the delayed phase showing enhancement of the soft tissue density around the testicular artery suggesting wall thickening and inflammation.

Digital subtraction angiography (DSA) was performed to confirm the arterial changes 1 week after the CT. Selective catheterization of the branches was performed from the abdominal aorta. The bilateral testicular arteries demonstrated irregular stenosis and ectasia in the proximal region, and the poor imaging indicating vascular occlusion in region distal to the spermatic cord (Fig. 2). Other branches of the abdominal aorta, such as the celiac, superior mesenteric, and right and left renal arteries, were normal.

Fig. 2.

DSA at PAN onset. Selectively catheterization of the right (A) and left (B) testicular arteries was performed. DSA demonstrated irregular stenosis and ectasia in the proximal region (arrowheads), and poor imaging suggesting vascular occlusion in the region distal to the spermatic cord (stars).

Pathologically, an analysis pf a biopsy specimen of a cutaneous nodule from the abdomen revealed lymphocyte and histiocyte infiltration and fibrosis of the medium arterial wall. Based on these findings polyarteritis nodosa (PAN) was clinically and pathologically diagnosed, in accordance with the 1990 classification criteria of the American College of Rheumatology (ACR) 1990 criteria (Table 1) [7] and the 2012 Chapel Hill Consensus Conference (CHCC) [1].

Table 1.

1990 ACR criteria for the classification of polyarteritis nodosa^a.

	Criterion	Definition
1.	Weight loss ≧4 kg	Loss of 4kg or more of body weight since illness began, not due to dieting or other factors.
2.	Livedo reticularis	Mottled reticular pattern over the skin of portions the extremities or torso.
3.	Testicular pain or tenderness	Pain or tenderness of the testicles, not due to infection, trauma, or other causes.
4.	Myalgias, weakness or leg tenderness	Diffuse myalgias (excluding shoulder and hip girdle) or weakness of muscle or tenderness of leg muscles.
5.	Mononeuropathy or polyneuropathy	Development of mononeuropathy, multiple mononeuropathies, or polyneuropathy.
6.	Diastolic BP >90 nnHg	Development of hypertension with the diastolic BP higher than 90 mmHg.
7.	Elevated BUN or creatinine	Elevation of BUN > 40 mg/dL or creatinine > 1.5 mg/dL, not due to dehydration or obstruction.
8.	Hepatitis B virus	Presence of hepatitis B virus surface antigen or antibody in serum
9.	Arteriographic abnormality	Arteriogram showing aneurysms or occlusions of the visceral arteries, not due to arteriosclerosis, fibromuscular dysplasia, or other noninflammatory causes.
10.	Biopsy of small or medium-sized artery containing PMN	Histologic changing showing the presence of granulocytes and mononuclear leukocytes in the artery wall.

^aFor classification purposes, a patient shall be said to have polyarteritis nodosa if at least 3 of these 10 criteria are present. The presence of any 3 criteria yields are a sensitivity of 82.2% and a specificity of 86.6%.

BP, blood pressure, BUN, blood urea nitrogen, PMN, polymorphonuclear neutrophil.

Despite prednisolone and cyclophosphamide therapy, the testicular pain remained and the inflammatory markers persisted at high levels. Six months after onset, CT and DSA were performed again to ascertain the disease status visually. CT demonstrated greater narrowing of the bilateral testicular arteries from the proximal to the distal region, including the bifurcations of the aorta and the vasculature near the testes (Fig. 3). DSA was performed in the right testicular artery but not the left testicular artery owing to the severe stenosis. The right testicular artery had narrowed to a string-like diameter without ectasia, and blood flow near the testis was almost completely absent (Fig. 4).

Fig. 3.

CT 6 months after onset. CT axial image of the arterial phase at the level of the spermatic cords. Bilateral testicular arteries showed greater narrowing than at the previous examination from the proximal to the and distal direction.

Fig. 4.

DSA 6 months after onset. Right testicular artery showed narrowing to a string-like diameter without ectasia.

Due to the diagnosis of sustained inflammatory activity in PAN, infliximab and methotrexate therapy introduced in place of cyclophosphamide, while reducing the dose of prednisolone gradually. The inflammatory findings in the blood test, cutaneous nodules and testicular pain had improved. Continuing the treatment currently, condition is stable.

Discussion

PAN is a necrotizing arteritis of medium or small arteries, and can involve any organ. General symptoms (93.1%), neurological (79.0%), urological and renal manifestations (50.6%), cutaneous (49.7%), and gastrointestinal manifestations (37.9%) are common findings. Orchitis or testicular tenderness, which are urological and renal manifestations, occur in 17.3% of patients [7]. Previous studies have reported that PAN can be localized to the testes, where it initially manifests orchitis or epididymitis [2]. In their autopsy report, Dahl et al. found testicular arterial lesions in 86% patients with periarteritis nodosa [8]. One of the ACR criteria for the diagnosis of PAN is testicular pain or tenderness (Table 1) [3], which should raise the index of suspicion of PAN when it occurs.

Previous studies have reported angiographic findings of renal, hepatic, splenic, superior mesenteric, inferior mesenteric and extremity arteries involvement in PAN. These arteries demonstrated multiple aneurysms or ectasia, with the small and medium-sized arteries also demonstrating irregular stenosis and/or occlusion [[4], [5], [6]].

In the present case, irregular stenosis and ectasia of the testicular arteries were found at the onset, with the stenosis showing signs of progression at an examination 6 months later. Arterial stenosis began from the distal or peripheral region and spread in the proximal direction. The ectasia the arteries possibly indicated increased blood flow with inflammation as well as occlusion of the arteries with granulation and scarring. Considering the dissociation of the blood flow in the distal testicular artery near the testis between the first CT and the first DSA, it may be inferred that the distal or peripheral blood flow near the testes had increased at first, then decreased as the peripheral arterial stenosis and occlusion progressed over 1 week. The irregular stenosis and ectasia of the proximal arteries near the bifurcation of the aorta might have arisen from a combination of the increased blood flow and the occlusion of distal or peripheral arteries and proximal arteries. These findings were compatible with PAN characterized by small and/or medium-sized arteritis.

The pathological cause of arteritis recognized into 4 phases: first the degenerative phase, second the acute inflammatory phase, third the granulation phase, and fourth scarring phase [9]. The first and second phases are reflected in the severe inflammation of the arteries throughout the body while the third and fourth phases are reflected in the ischemia of the involved organs [9]. In this case, we probably observed the change of the arteries diameter over time reflected to the phases of arteritis.

PAN is diagnosed on the basis of clinical, pathological or angiographic findings. Pagnoux et al. [7] reported 70.1% of patients had at least 1 positive biopsy finding of vasculitis mainly in muscle, nerve or skin issue while 18.7% of patients had unremarkable findings.

Angiography may be useful as a diagnostic alternative to a tissue biopsy or surgery, as demonstrated in the present case, which highlighted the angiographic findings of the testicular arteries and it can be useful for diagnosing PAN localized in the testes. The change in the arteries diameter over time leading to progressive stenosis may be specific to PAN. A nonsurgical, diagnostic method is useful especially for young male patients as it will not adversely affect fertility. However, angiography has the disadvantage of being unable completely to rule out malignancies.

Conclusion

The present case report discussed the angiographic findings of the testicular arteries in PAN, which included irregular stenosis and ectasia. The angiographic findings of PAN can change over time, reflecting progression of the disease.

Patient consent

Written informed consent was obtained from the patient for the publication of this case report and any accompanying images.