World J Nephrol Urol

World Journal of Nephrology and Urology, ISSN 1927-1239 print, 1927-1247 online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Nephrol Urol and Elmer Press Inc

Journal website http://www.wjnu.org

Case Report

Volume 7, Number 1, March 2018, pages 32-37

Minocycline-Induced Polyarteritis Nodosa Presenting With Testicular Pain: A Case Report and Selected Review of the Literature

Figure 1. Left paratesticular tissue with perivascular infiltrates containing of lymphocytes and plasma cells (H&E, 20 × original magnification).

Figure 2. Left paratesticular tissue with focal necrotizing vasculitis of small and medium sized vessels and perivascular infiltrates containing of lymphocytes and plasma cells (H&E, 40 × original magnification).

**Table 1.** A Selected Review of the Literature on Testicular Polyarteritis Nodosa [3-18]
Study, date	Patient age/final Dx	CC	Labs and ultrasound	Pathology	Tx	Sx after tx	Significance
ANA: anti-nuclear antibody; ANCA: anti-nuclear cytoplasmic antibody; Asymp-: asymptomatic; Avg: average; Bx: biopsy; CRP: C-reactive protein; C/W: consistent with; ESR: erythrocyte sedimentation rate; PAN: polyarteritis nodosa; Sx: symptoms; Tx: treatment; U/S: ultrasound.
Lenert, 2013 [3]	21/minocycline-induced systemic PAN	Left testicular pain + systemic sx	Labs: elevated ESR, CRP, (+) p-ANCA, (+) ANA; U/S: wedge-shaped lesion	Medium-size testicular artery with mononuclear cell infiltration and area of testicular necrosis	Removal of minocycline, short course of prednisone and hydroxychloroquine	Asymp- and disease free at 2 years	Systemic vasculitis associated with chronic minocycline use
Gervaise, 2014 [4]	28/systemic PAN	Right testicular pain	Labs: mildly elevated CRP; U/S: no Doppler flow in right testis with numerous hypoechogenic areas and some areas of normal parenchyma	Gross: heterogeneous in appearance with alternating areas of ischemia without necrosis and healthy parenchyma c/w acute vasculitis	IV prednisolone and cyclophosphamide	Asymp-	Diagnosis of testicular vasculitis on CT angio: thrombosis of distal testicular artery, no confirmed biopsy
Bing, 2012 [5]	46/systemic PAN	Left flank pain with gross hematuria after running	Labs: elevated ESR and CRP, anemia, (-) ANA, (-) ANCA; renal U/S: left-sided, upper pole, pelvi-calyceal distension and peri-nephric edema	N/A	Glucocorticoid, cyclophosphamide, methotrexate	Asym- and disease free at 2 years	Diagnosis based on presence of aneurysms on left renal angiogram
Toepfer, 2011 [6]	55/systemic PAN	Left testicular pain, with recurrence on the right 3 weeks after initial evaluation, recurrent systemic ischemic events	Labs: all (-); U/S: decreased blood flow	Testicular specimens: interstial hemorrhage and focal atrophy; Abdominal wall skin bx: thrombotic vasculopathy with leukocytoclastic vasculitis	Bilateral orchiectomy, methylprednisone + cyclophosphamide	Recurrence of ischemic events at 3 weeks and 5 weeks; asymp- after systemic tx at 6 months	Asynchronous testicular necrosis as initial sign of systemic PAN
Ahmad, 2010 [7]	65/systemic PAN	Left testicular pain and swelling, developed frank painless hematuria during workup	Labs: (+) ANCA, elevated ESR; U/S: mycotic aneurysmal lesions of the testicle	N/A	Glucocorticoid	“Cinically well”	Left renal hematoma on CT scan, small aneurysms found in both kidneys on angiography
Meeuwissen, 2008 [8]	72, 61, 28/systemic PAN	Testicular pain preceeding systemic symptoms (1), concurrent systemic sx and testicular pain (2)	Labs: elevated ESR, CRP, (-) ANCA, (-) ANA, anemia; U/S: heterogenic, enlarged testis	Gross: edematous, blue colored testis with multiple necrotic areas; Microscopic: segmental destruction of vessel wall of small and medium-sized arteries by mononuclear inflammatory infiltrate; fibrinoid necrosis and thrombi	Orchiectomy, methylprednisolone taper (after onset of systemic symptoms)	Asymp- and disease free at 16 months - 80 months	Testicular involvement as prominent sign of PAN
Kolar, 2007 [9]	29/systemic PAN	Right scrotal pain + systemic sx	Labs: elevated ESR, CRP, (-) ANCA; U/S: enlarged and swollen right epididymis with reduced blood flow; reduced testicular artery flow	N/A	Glucocorticoids + cyclophosphamide	N/A	Improved testicular artery flow after systemic treatment without need for orchiectomy
Susanto, 2003 [10]	74/systemic PAN	Left testicular pain + systemic sx	Labs: elevated ESR, CRP, anemia, leukocytosis, microscopic hematuria; (-) ANCA; U/S: small right testicular cyst and mild enlargement of left testicle with normal epididymis	Skin/muscle bx: vasculitis of medium vessels with mixed cellular infiltrate in intramuscular arterioles and their branches	Oral prednisone (1 mg/kg/day) and cyclophosphamide (2 mg/kg/day) × 6 months	Asymp- at 1 year	Febrile episode of epididymo-orchitis as initial manifestation of PAN
Eilber, 2001 [11]	43/systemic PAN	Hematuria, left testicular mass, systemic sx	Labs: elevated ESR, (+) ANA; U/S: suspicious heterogeneous intratesticular lesion	Inflammatory infiltrate and thrombosis in vessel lumina, necrosis of intimal layer	Orchiectomy only	Asymp-	PAN presenting with hematuria and testicular lesion
Brimo, 2011 [12]	35 (avg) 23-53 (range)/isolated testicular PAN (12), systemic PAN (2)	Testicular pain (86%), mass (7%)	Labs: all negative except 2 with elevated CRP and ESR, (-) ANCA; 1 with (+) ANA; U/S: hypoechoic mass suspicious for cancer	Transmural necrotizing inflammation of small to medium-sized ateries with fibrinoid necrosis and acute inflammation	Orchiectomy, systemic treatment: predisone, or prednisone + cytoxan (in half of isolated cases and all of systemic cases)	N/A	Case report of testicular vasculitis, 14 confirmed to be PAN, half of isolated cases still received systemic treatment
Fraenkel-Rubin, 2002 [13]	26/iIsolated testicular PAN	Left testicular pain	Labs: negative ESR, CRP, ANA, ANCA, CBC; U/S: diffuse damage consistent with interstitial process	Fibrinoid necrosis of medium and small sized arteries with acute transmural inflammation with lymphoplasmacytic and eosinophilic infiltrates	Orchiectomy only	Asymp- and disease free at 2.5 years	Use of Birmingham Vasculitis Activity Score (BVAS) in determining need for systemic treatment for isolated PAN
Pastor-Navarro, 2007 [14]	26/isolated testicular PAN	Painful bilateral testicular swelling	Labs: all (-); U/S: multiple non-vascularized, heterogeneous, hypoechoic focal lesions; small reactive hydrocele	Areas of intraparenchymal hemorrhage, fibrinoid necrosis, pleomorphic infiltration	Right orchiectomy, glucocorticoid	Asymp- at 1 year	Concurrent bilateral testicular involvement
Tanuma, 2003 [15]	40/isolated testicular PAN	Left testicular pain, with recurrence on right 16 months after initial diagnosis	Labs: (+) ANA; U/S: avascularity of bilateral testes	Fibrinoid necrosis of small and medium sized arteries with severe inflammatory infiltrate and near obstruction of arterial lumen	Bilateral orchiectomy	Asymp- and disease free at 22 months	Recurrent testicular PAN
Mukamel, 1995 [16]	28, 35/isolated testicular PAN	Right painful testicular swelling and mass	Labs: all (-); U/S: intratesticular hyper- and hypoechogenic areas (1); normal with hydrocele (1)	Intratesticular hemorrhage and fibrosis, segmental fibrinoid necrosis, thrombosis, and perivascular fibrosis of small arteries; some aneurysmal dilatation	Orchiectomy only	Asymp- and disease free at 2 - 3 years	Isolated testicular PAN
Warfield, 1994 [17]	19/isolated testicular PAN	Left testicular pain and swelling with recurrence in right testicle 12 months later	Labs: elevated ESR and CRP, (-) ANCA; U/S: heterogeneous echo pattern including areas suggestive of cystic change	Gross: scattered areas of hemorrhage of lower pole of testis; Microscopic: patchy, necrotizing vasculitis affecting medium and small arteries; fibrinoid necrosis of walls and transmural infiltrate of PMNs and lymphocytes	Left orchiectomy + cyclophosphamide × 1month, azathioprine and oral prednisone with short-term increase after recurrence on right side, long-term low dose prednisolone	Recurrence of sx at 12 months; asymp- and disease free at 18 months	Recurrence of sx while on systemic therapy
Fleischmann, 2007 [18]	21/isolated testicular PAN + metastatic mixed germ cell tumor	Left painful scrotal swelling	Labs: N/A; U/S: enlarged left epididymis and calcifications	Mixed germ cell tumor of left testis; circumferential, transmural fibrinoid necrosis, inflammatory infiltrates composed of neutrophils and monocytes in or around the walls of small to medium-sized arteries	Orchiectomy only	Asymp- and disease free at 2 years	Isolated PAN presenting with mixed germ cell tumor

Table 1. A Selected Review of the Literature on Testicular Polyarteritis Nodosa [3-18]

Study, date

Patient age/final Dx

Labs and ultrasound

Pathology

Sx after tx

Significance

ANA: anti-nuclear antibody; ANCA: anti-nuclear cytoplasmic antibody; Asymp-: asymptomatic; Avg: average; Bx: biopsy; CRP: C-reactive protein; C/W: consistent with; ESR: erythrocyte sedimentation rate; PAN: polyarteritis nodosa; Sx: symptoms; Tx: treatment; U/S: ultrasound.

Lenert, 2013 [3]

21/minocycline-induced systemic PAN

Left testicular pain + systemic sx

Labs: elevated ESR, CRP, (+) p-ANCA, (+) ANA; U/S: wedge-shaped lesion

Medium-size testicular artery with mononuclear cell infiltration and area of testicular necrosis

Removal of minocycline, short course of prednisone and hydroxychloroquine

Asymp- and disease free at 2 years

Systemic vasculitis associated with chronic minocycline use

Gervaise, 2014 [4]

28/systemic PAN

Right testicular pain

Labs: mildly elevated CRP; U/S: no Doppler flow in right testis with numerous hypoechogenic areas and some areas of normal parenchyma

Gross: heterogeneous in appearance with alternating areas of ischemia without necrosis and healthy parenchyma c/w acute vasculitis

IV prednisolone and cyclophosphamide

Asymp-

Diagnosis of testicular vasculitis on CT angio: thrombosis of distal testicular artery, no confirmed biopsy

Bing, 2012 [5]

46/systemic PAN

Left flank pain with gross hematuria after running

Labs: elevated ESR and CRP, anemia, (-) ANA, (-) ANCA; renal U/S: left-sided, upper pole, pelvi-calyceal distension and peri-nephric edema

N/A

Glucocorticoid, cyclophosphamide, methotrexate

Asym- and disease free at 2 years

Diagnosis based on presence of aneurysms on left renal angiogram

Toepfer, 2011 [6]

55/systemic PAN

Left testicular pain, with recurrence on the right 3 weeks after initial evaluation, recurrent systemic ischemic events

Labs: all (-); U/S: decreased blood flow

Testicular specimens: interstial hemorrhage and focal atrophy; Abdominal wall skin bx: thrombotic vasculopathy with leukocytoclastic vasculitis

Bilateral orchiectomy, methylprednisone + cyclophosphamide

Recurrence of ischemic events at 3 weeks and 5 weeks; asymp- after systemic tx at 6 months

Asynchronous testicular necrosis as initial sign of systemic PAN

Ahmad, 2010 [7]

65/systemic PAN

Left testicular pain and swelling, developed frank painless hematuria during workup

Labs: (+) ANCA, elevated ESR; U/S: mycotic aneurysmal lesions of the testicle

N/A

Glucocorticoid

“Cinically well”

Left renal hematoma on CT scan, small aneurysms found in both kidneys on angiography

Meeuwissen, 2008 [8]

72, 61, 28/systemic PAN

Testicular pain preceeding systemic symptoms (1), concurrent systemic sx and testicular pain (2)

Labs: elevated ESR, CRP, (-) ANCA, (-) ANA, anemia; U/S: heterogenic, enlarged testis

Gross: edematous, blue colored testis with multiple necrotic areas; Microscopic: segmental destruction of vessel wall of small and medium-sized arteries by mononuclear inflammatory infiltrate; fibrinoid necrosis and thrombi

Orchiectomy, methylprednisolone taper (after onset of systemic symptoms)

Asymp- and disease free at 16 months - 80 months

Testicular involvement as prominent sign of PAN

Kolar, 2007 [9]

29/systemic PAN

Right scrotal pain + systemic sx

Labs: elevated ESR, CRP, (-) ANCA; U/S: enlarged and swollen right epididymis with reduced blood flow; reduced testicular artery flow

N/A

Glucocorticoids + cyclophosphamide

N/A

Improved testicular artery flow after systemic treatment without need for orchiectomy

Susanto, 2003 [10]

74/systemic PAN

Left testicular pain + systemic sx

Labs: elevated ESR, CRP, anemia, leukocytosis, microscopic hematuria; (-) ANCA; U/S: small right testicular cyst and mild enlargement of left testicle with normal epididymis

Skin/muscle bx: vasculitis of medium vessels with mixed cellular infiltrate in intramuscular arterioles and their branches

Oral prednisone (1 mg/kg/day) and cyclophosphamide (2 mg/kg/day) × 6 months

Asymp- at 1 year

Febrile episode of epididymo-orchitis as initial manifestation of PAN

Eilber, 2001 [11]

43/systemic PAN

Hematuria, left testicular mass, systemic sx

Labs: elevated ESR, (+) ANA; U/S: suspicious heterogeneous intratesticular lesion

Inflammatory infiltrate and thrombosis in vessel lumina, necrosis of intimal layer

Orchiectomy only

Asymp-

PAN presenting with hematuria and testicular lesion

Brimo, 2011 [12]

35 (avg) 23-53 (range)/isolated testicular PAN (12), systemic PAN (2)

Testicular pain (86%), mass (7%)

Labs: all negative except 2 with elevated CRP and ESR, (-) ANCA; 1 with (+) ANA; U/S: hypoechoic mass suspicious for cancer

Transmural necrotizing inflammation of small to medium-sized ateries with fibrinoid necrosis and acute inflammation

Orchiectomy, systemic treatment: predisone, or prednisone + cytoxan (in half of isolated cases and all of systemic cases)

N/A

Case report of testicular vasculitis, 14 confirmed to be PAN, half of isolated cases still received systemic treatment

Fraenkel-Rubin, 2002 [13]

26/iIsolated testicular PAN

Left testicular pain

Labs: negative ESR, CRP, ANA, ANCA, CBC; U/S: diffuse damage consistent with interstitial process

Fibrinoid necrosis of medium and small sized arteries with acute transmural inflammation with lymphoplasmacytic and eosinophilic infiltrates

Orchiectomy only

Asymp- and disease free at 2.5 years

Use of Birmingham Vasculitis Activity Score (BVAS) in determining need for systemic treatment for isolated PAN

Pastor-Navarro, 2007 [14]

26/isolated testicular PAN

Painful bilateral testicular swelling

Labs: all (-); U/S: multiple non-vascularized, heterogeneous, hypoechoic focal lesions; small reactive hydrocele

Areas of intraparenchymal hemorrhage, fibrinoid necrosis, pleomorphic infiltration

Right orchiectomy, glucocorticoid

Asymp- at 1 year

Concurrent bilateral testicular involvement

Tanuma, 2003 [15]

40/isolated testicular PAN

Left testicular pain, with recurrence on right 16 months after initial diagnosis

Labs: (+) ANA; U/S: avascularity of bilateral testes

Fibrinoid necrosis of small and medium sized arteries with severe inflammatory infiltrate and near obstruction of arterial lumen

Bilateral orchiectomy

Asymp- and disease free at 22 months

Recurrent testicular PAN

Mukamel, 1995 [16]

28, 35/isolated testicular PAN

Right painful testicular swelling and mass

Labs: all (-); U/S: intratesticular hyper- and hypoechogenic areas (1); normal with hydrocele (1)

Intratesticular hemorrhage and fibrosis, segmental fibrinoid necrosis, thrombosis, and perivascular fibrosis of small arteries; some aneurysmal dilatation

Orchiectomy only

Asymp- and disease free at 2 - 3 years

Isolated testicular PAN

Warfield, 1994 [17]

19/isolated testicular PAN

Left testicular pain and swelling with recurrence in right testicle 12 months later

Labs: elevated ESR and CRP, (-) ANCA; U/S: heterogeneous echo pattern including areas suggestive of cystic change

Gross: scattered areas of hemorrhage of lower pole of testis; Microscopic: patchy, necrotizing vasculitis affecting medium and small arteries; fibrinoid necrosis of walls and transmural infiltrate of PMNs and lymphocytes

Left orchiectomy + cyclophosphamide × 1month, azathioprine and oral prednisone with short-term increase after recurrence on right side, long-term low dose prednisolone

Recurrence of sx at 12 months; asymp- and disease free at 18 months

Recurrence of sx while on systemic therapy

Fleischmann, 2007 [18]

21/isolated testicular PAN + metastatic mixed germ cell tumor

Left painful scrotal swelling

Labs: N/A; U/S: enlarged left epididymis and calcifications

Mixed germ cell tumor of left testis; circumferential, transmural fibrinoid necrosis, inflammatory infiltrates composed of neutrophils and monocytes in or around the walls of small to medium-sized arteries

Orchiectomy only

Asymp- and disease free at 2 years

Isolated PAN presenting with mixed germ cell tumor