   |
|
DERMATOPATHOLOGY ROUND |
|
| Year : 2022 | Volume
: 67
| Issue : 6 | Page : 721-724 |
|
| Coexistence of superficial thrombophlebitis and cutaneous venulitis in behçet's disease: Report of 5 cases |
|
|
Mayu Sato1, Ko-Ron Chen2, Toshiyuki Yamamoto1
1 From the Department of Dermatology, Fukushima Medical University, Hikarigaoka, Fukushima, Japan
2 Meguro Chen Dermatology Clinic, Tokyo, Japan
| Date of Web Publication | 23-Feb-2023 |
Correspondence Address:
Toshiyuki Yamamoto
Department of Dermatology, Fukushima Medical University, Hikarigaoka 1, Fukushima 960-1295
Japan
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/ijd.ijd_229_22
|
|
 Abstract | | |
Previous studies have shown that erythema nodosum-like lesions in patients with Behçet's disease show cutaneous vasculitis of either phlebitis or dermal venulitis. To analyse the clinicopathological characteristics of superficial thrombophlebitis as well as cutaneous venulitis in Behçet's disease. We re-evaluated the histopathological features of superficial thrombophlebitis in patients with Behçet's disease. Five patients, one man and four women, developed superficial thrombophlebitis on the lower extremities. Two of the patients had vascular Behçet's disease, both also developed deep vein thrombosis. One patient had intestinal Behçet's disease. In all cases, venulitis in the overlying lower dermis or adjacent subcutis spreading from the main affected subcutaneous thrombophlebitis lesions was observed. Both neutrophilic venulitis (n = 2) and lymphocytic venulitis (n = 3) were observed at the same depth level or upper/lower location of the thrombophlebitis in the same specimens. In addition, concurrent venulitis with fibrin thrombus and fibrinoid necrosis was observed in one case, suggesting that fibrin thrombus affected both venules and muscular veins. By contrast, arteritis or arteriolitis at the same depth level was not observed. Our results showed histopathological features of coexistent thrombophlebitis and venulitis without involvement of either arteries or arterioles in the biopsied specimens of superficial thrombophlebitis. Further studies are necessary to support that those unique histopathological findings are the characteristic features and significant diagnostic indicators of Behçet's disease.
Keywords: Behçet's disease, lymphocytic venulitis, neutrophilic vascular reaction, neutrophilic venulitis, thrombophlebitis
How to cite this article:
Sato M, Chen KR, Yamamoto T. Coexistence of superficial thrombophlebitis and cutaneous venulitis in behçet's disease: Report of 5 cases. Indian J Dermatol 2022;67:721-4 |
How to cite this URL:
Sato M, Chen KR, Yamamoto T. Coexistence of superficial thrombophlebitis and cutaneous venulitis in behçet's disease: Report of 5 cases. Indian J Dermatol [serial online] 2022 [cited 2023 Mar 23];67:721-4. Available from: https://www.e-ijd.org/text.asp?2022/67/6/721/370282 |
| Introduction | |  |
Oral aphthae, genital ulcers, acneiform papulopustular eruptions, erythema nodosum-like lesions and superficial thrombophlebitis are representative mucocutaneous manifestations of Behçet's disease. According to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides, Behçet's disease is classified as a variable vessel vasculitis, and cutaneous lesions are induced by a vessel-based neutrophilic reaction with leucocytoclasia and cutaneous small vessel vasculitis of mostly venules and/or thrombophlebitis.[1] Cutaneous vasculopathy in Behçet's disease comprises; a lymphocytic or granulomatous vasculitis with or without thrombosis, necrosis or mural fibrin deposition; a paucicellular thrombogenic vasculopathy; and a neutrophilic vascular reaction that predominantly involves capillaries and veins.[2],[3]
Superficial thrombophlebitis is the most frequent vascular symptom in Behçet's disease, and presents as erythematous, tender, subcutaneous nodules occasionally confused with erythema nodosum but arranged in a linear fashion.[4] Cutaneous venulitis is sometimes seen in erythema nodosum-like skin lesions in patients with Behçet's disease;[5],[6],[7] however, there are few studies focusing on cutaneous vasculitis in Behçet's disease. We herein describe rare cases in which superficial thrombophlebitis and venulitis coexisted in the same biopsy specimen.
| Materials and Methods | | |
We re-evaluated the histopathological features of the biopsy specimens taken from patients who had been diagnosed with definite and probable Behçet's disease in our department between 2005 and 2019. The biopsied tissue specimens were submitted for haematoxylin-eosin and Elastica van Gieson staining. As positive controls, three cases of thrombophlebitis unassociated with Behçet's disease were examined. This study was approved by the Institutional Review Board committee of Fukushima Medical University.
| Results | | |
Histopathological features revealed five cases of superficial thrombophlebitis. The patients were four women and one man, aged 25–52 years (mean: 38 years old) and all of them had developed painful multiple subcutaneous nodules on the lower extremities [Figure 1]. Other mucocutaneous signs were oral aphtha (n = 5) and genital ulcer (n = 2), whereas folliculitis and erythema nodosum were not observed. According to the International Criteria for Behçet's Disease,[8] three patients almost certainly had Behçet's disease, one was highly likely and one was probable Behçet's disease. Two patients had vascular Behçet's disease, both also developed deep vein thrombosis. One had intestinal Behçet's disease. One of the five patients had a familial history of Behçet's disease. Biopsy was taken from erythema nodosum-like infiltrative subcutaneous nodules on the thigh (n = 1) and lower leg (n = 4). | Figure 1: A representative clinical picture showing subcutaneous nodule in a linear distribution
Click here to view |
In all cases, thrombophlebitis was observed in the lower dermis and subcutis, and Elastica van Gieson staining revealed an affected subcutaneous muscular vein characterised by concentric bundles of separate muscular layers encircled by elastic fibres and irregular uneven intimal elastic fibre with infiltration of inflammatory cells between the separate muscular layers and central luminal fibrin thrombus [Figure 2], which was the characteristic features of subcutaneous thrombophlebitis.[9] In addition, neutrophilic vasculitis (n = 2) or lymphocytic vasculitis (n = 3) coexisted with thrombophlebitis lesions in the same biopsy specimens. In Case 1, in addition to thrombophlebitis [Figure 3]a, venulitis with fibrinoid necrosis in the blood vessels was observed in the underlying subcutaneous tissues [Figure 3]b. In Case 2, lymphocytic vasculitis around the thrombus was observed, indicating lymphocyte infiltration in and around the edematous vessel wall, as well as the disappearance of endothelial cells [Figure 4]. By contrast, arteritis or arteriolitis at the same level was not observed [Figure 4]. In Case 3, a unique histopathological feature of subcutaneous thrombophlebitis with coexistent venulitis in the overlying lower dermis showing fibrin thrombus and fibrinoid necrosis in the blood vessels was observed [Figure 5]a, [Figure 5]b. In addition, venulitis with fibrinoid degeneration and a marked angiocentric lymphocytic infiltration in and around the degenerated swollen vessel wall was also observed at a lower level than that of the thrombophlebitis lesion [Figure 5]c. In the remaining two cases, lymphocytic vasculitis was observed near the thrombophlebitis lesion (Case 4), and at the same depth level as the thrombophlebitis lesion in the subcutis (Case 5). In the control biopsy specimens, no findings of venulitis around the subcutaneous thrombophlebitis were observed. Patient characteristics and histopathological features are summarised in [Table 1]. | Figure 2: An affected subcutaneous muscular vein characterised by concentric bundles of separate muscular layers encircled by elastic fibres (arrows) and irregular uneven intimal elastic fibre (arrow head) with infiltration of inflammatory cells between the separate muscular layers and central luminal fibrin thrombus revealed the characteristic features of subcutaneous thrombophlebitis (Elastica van Gieson staining, original magnification ×200)
Click here to view |
 | Figure 3: (a) Thrombophlebitis affecting the muscular vein located at the dermal-subcutaneous junction with marked inflammatory cell infiltration. At the subcutis, focal panniculitis is observed (enclosed in a square). (b) Higher magnification shows venulitis with fibrinoid necrosis of the vessel walls. (haematoxylin-eosin stain, original magnification: a; ×40, b; ×400)
Click here to view |
 | Figure 4: Subcutaneous medium-sized thrombophlebitis, and at the adjacent thrombophlebitis, lymphocytic vasculitis with a marked angiocentric infiltrate and partial vessel destruction was observed (enclosed in a square) (haematoxylin-eosin stain, original magnification ×100)
Click here to view |
 | Figure 5: (a) Thrombophlebitis in the subcutaneous tissue as well as venulitis with fibrin thrombus in the overlying lower dermis (enclosed in a square). (b) Higher magnification showed leucocytoclastic venulitis with fibrin thrombus and mild fibrinoid necrosis in the vessel wall. (c) In the lower dermis, lymphocytic venulitis with partial vessel wall fibrinoid necrosis and a marked angiocentric mononuclear cell infiltration in and around the degenerated swollen vessel wall was observed. (haematoxylin-eosin stain, original magnification: a; ×40, b; ×200, c; ×200)
Click here to view |
| Discussion | | |
Superficial thrombophlebitis is a representative skin condition among various mucocutaneous conditions associated with Behçet's disease. In our case series, thrombophlebitis was observed more commonly in female patients, although the number was small. In our five patients with Behçet's disease who had developed superficial thrombophlebitis, both thrombophlebitis and venulitis coexisted in the same biopsied specimens. These findings suggest that cutaneous venulitis is a major skin manifestation associated with Behçet's disease. Vasculitis with both pan-dermal venulitis and muscular vessel vasculitis can occur in Behçet's disease.[3] Moreover, pauci-inflammatory thrombogenic vasculopathy and/or lymphocytic vasculitis are suggested to occur in patients with Behçet's disease.[2] Dermal venulitis is rarely observed in biopsied specimens of erythema nodosum-like lesions associated with Behçet's disease, and there are few studies focusing on cutaneous vasculitis in Behçet's disease. Chen et al.[5] reported that in 20 cases of erythema nodosum-like lesions, lymphocytic vasculitis and leucocytoclastic vasculitis were observed in 31% and 17%, respectively, and that the cutaneous vasculitis in the erythema nodosum-like lesions was mostly venulitis or phlebitis. In their report, 1 of the 20 cases showed subcutaneous medium-sized thrombophlebitis and dermal necrotising venulitis in the same specimen. Kim and LeBoit[6] examined 11 sections of erythema nodosum-like lesions in cases with Behçet's disease, and detected lymphocytic vasculitis in 6 sections, as well as leucocytoclastic vasculitis in 4 sections. Both lymphocytic vasculitis and leucocytoclastic vasculitis were observed in different vessels in the same specimens.[6] Misago et al.[7] examined their 11 patients with phlebitis type, and found thrombophlebitis in 3 patients; however, the coexistence of venulitis was not mentioned in their report. In a case series by Chen et al.,[5] one patient presented with erythema nodosum-like lesions with subcutaneous thrombophlebitis, in which lymphocytic vasculitis coexisted in the overlying deep dermis; however, thereafter, there have been very few reports detailing the unique coexistence of these findings.
In conclusion, our data suggest that cutaneous venulitis/phlebitis is not rare in Behçet's disease, and coexistence of subcutaneous phlebitis with overlying dermal venulitis without involvement of arteries/arterioles are the characteristic histopathological feature of Behçet's disease.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | | |
| 1. | Sunderkötter CH, Zelger B, Chen K-R, Requena L, Piette W, Carlson JA, et al. Nomenclature of cutaneous vasculitis: dermatologic addendum to the 2012 revised international Chapel Hill consensus conference nomenclature of vasculitides. Arthritis Rheumatol 2018;70:171-84.  |
| 2. | Crowson AN, Mihm MC Jr, Magro CM. Cutaneous vasculitis: A review. J Cutan Pathol 2003;30:161-73. |
| 3. | Chen KR, Carlson JA. Clinical approach to cutaneous vasculitis. Am J Clin Dermatol 2008;9:71-92. |
| 4. | Alpsoy E. Behçet's disease: A comprehensive review with a focus on epidemiology, etiology and clinical features, and management of mucocutaneous lesions. J Dermatol 2016;43:620-32. |
| 5. | Chen KR, Kawahara Y, Miyakawa S, Nishikawa T. Cutaneous vasculitis in Behçet's disease: A clinical and histopathologic study of 20 patients. J Am Acad Dermatol 1997;36:689-96. |
| 6. | Kim B, LeBoit PE. Histopathologic features of erythema nodosum-like lesions in Behçet's disease: A comparison with erythema nodosum focusing on the role of vasculitis. Am J Dermatopathol 2000;22:379-90. |
| 7. | Misago N, Tada Y, Koarada S, Narisawa Y. Erythema nodosum-like lesions in Behçet's disease: A clinicopathological study of 26 cases. Acta Derm Venereol 2012;92:681-6. |
| 8. | Davatchi F, Assaad-Khalil S, Calamia KT, Crook JE, Sadeghi-Abdollahi B, Schirmer M, et al. The international criteria for Behçet's disease (ICBD): a collaborative study of 27 countries on the sensitivity and specificity of the new criteria. J Eur Acad Dermatol Venereol 2014;28:338-47. |
| 9. | Chen KR. The misdiagnosis of superficial thrombophlebitis as cutaneous polyarteritis nodosa: Features of the internal elastic lamina and the compact concentric muscular layer as diagnostic pitfalls. Am J Dermatopathol 2010;32:688-93. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5] |
|
|
|
|
|
|
|
|
|
|
|
|
| Article Access Statistics | | | Viewed | 306 | | | Printed | 16 | | | Emailed | 0 | | | PDF Downloaded | 8 | | | Comments | [Add] | | |
|
|
