|Year : 2016 | Volume
| Issue : 2 | Page : 89-94
Study of predictive value of capillaroscopic pattern and serum level of interleukin-17 in rheumatoid vasculitis patients
Hamdy K Koryem1, Manal Y Tayel2, Sarah S Eltawab1, Reham F Moftah3, Omneya E Elazzazy4
1 Department of Physical Medicine, Rheumatology and Rehabilitation; Faculty of Medicine, Alexandria University, Alexandria, Egypt
2 Department of Internal Medicine; Faculty of Medicine, Alexandria University, Alexandria, Egypt
3 Department of Clinical Pathology; Faculty of Medicine, Alexandria University, Alexandria, Egypt
4 Department of Physical Medicine, Rheumatology and Rehabilitation, Alexandria University, Alexandria, Egypt
|Date of Submission||06-Apr-2016|
|Date of Acceptance||08-Apr-2016|
|Date of Web Publication||21-Oct-2016|
Omneya E Elazzazy
Doctor degree in Physical Medicine, Rheumatology and Rehabilitation, Faculty of Medicine, Alexandria University, Alexandria
Source of Support: None, Conflict of Interest: None
The aim of this study was to investigate nailfold capillaroscopic (NC) abnormalities and serum interleukin (IL)-17) level among rheumatoid arthritis (RA) patients with or without vasculitis.
Patients and methods
The study was carried on a group of RA Egyptian patients (n=40) who were diagnosed with RA based on ACR criteria. These 40 patients were further divided into two groups. Group 1 included RA patients with clinical signs of skin vasculitis and NC changes (n=6). Group 2 included RA patients with no clinical signs of skin vasculitis and no NC changes (n=34). All patients were subjected to demographic data collection, clinical examination, Disease Activity Score (DAS) 28 calculation, laboratory measurement (including erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, antinuclear antibody, antineutrophil cytoplasmic antibody, anticyclic citrullinated peptide, and IL-17), and NC examination. In addition, group 1 (n=6) was further subjected to electrophysiological evaluation by peripheral nerve conduction studies.
Significantly elevated levels of IL-17 and characteristic NC changes were seen in RA vasculitis patients.
Rheumatoid vasculitis is associated with significantly elevated levels of serum IL-17 and characteristic NC changes.
Keywords: interleukin-17, nailfold capillaroscopy, rheumatoid vasculitis
|How to cite this article:|
Koryem HK, Tayel MY, Eltawab SS, Moftah RF, Elazzazy OE. Study of predictive value of capillaroscopic pattern and serum level of interleukin-17 in rheumatoid vasculitis patients. Al-Azhar Assiut Med J 2016;14:89-94
|How to cite this URL:|
Koryem HK, Tayel MY, Eltawab SS, Moftah RF, Elazzazy OE. Study of predictive value of capillaroscopic pattern and serum level of interleukin-17 in rheumatoid vasculitis patients. Al-Azhar Assiut Med J [serial online] 2016 [cited 2019 Sep 23];14:89-94. Available from: http://www.azmj.eg.net/text.asp?2016/14/2/89/192647
| Introduction|| |
Rheumatoid vasculitis (RV) is the most serious systemic disease manifestation of rheumatoid arthritis (RA) and it manifests almost exclusively in RA patients with rheumatoid autoantibodies and often occurs in the context of other extra-articular manifestations. RV is defined as a clinicopathological manifestation of RA characterized by tissue damage or ischemia verified pathologically by vasculitis ,.
Clinical reports have estimated the prevalence of RV at less than 1–5%, whereas autopsy studies have reported a prevalence of 15–31% ,.
Three histological patterns of vasculitis may be seen:
- A necrotizing leukocytoclastic vasculitis of dermal venules is seen in patients with palpable purpura, hemorragic bullae, maculopapular erythema, and erythema elevatum diutinum .
- An acute or healing arteritis of dermal subcutaneous vessels similar to that seen in polyarteritis nodosa is seen in patients with subcutaneous nodules, livido reticularis, and ulcers ,.
- Other histological patterns that can be seen include folliculocentric microabscess formation resembling dermatitis herpitiform and granulomatous vasculitis composed mainly of lymphocytes and histocytes .
- Postulated mechanisms of vessel wall destruction with RV include the following :
- Autoantibody targeting of the vessel .
- Incidental inflammation due to deposition of immune complexes ,.
- Collateral damage due to a local antigen-driven cellular immune response .
RV may involve virtually any organ of the body, but the most common sites of involvement are the skin and peripheral nerves; as reported in many series, the skin or peripheral nerves are involved in more than 80% of RV patients. Major organ system involvement of the heart, bowel, or kidney is much less common but can lead to significant morbidity and mortality, including myocardial infarction, bowel ischemia, and renal failure. Although central nervous system involvement is rare, many case reports describe its occurrence ,.
Interleukin (IL)-17 or IL-17A is a member of a group of cytokines called IL-17 family (including IL-17B, IL-17C, IL-17D, IL-17E, and IL-17F). Among all members, the biological functions and regulations of IL-17A and IL-17F are best understood ,. Specialized T-cells, called Th17 cells, are the major sources of IL-17A and IL-17F in many types of adaptive immunity. However, recently, other contributors to IL-17A and IL-17F production, mainly in the innate arm of the immune system,were identified .
Although crucial in protecting the host from invasion by many types of pathogens, dysregulated IL-17 production can result in excessive proinflammatory cytokine expression and chronic inflammation, which lead to tissue damage and autoimmunity ,.
IL-17 has a role in chronic vascular inflammation of atherosclerosis and possibly hypertensive vascular changes, whereas in acute inflammation IL-17 is elevated and may be causally involved in the autoimmune vasculitides ,,,,.
Nailfold capillaroscopy (NC) was used during the beginning of the 20th century, to show in detail the abnormalities that characterize the involvement of microvasculature during Raynaud’s phenomenon in systemic sclerosis .
NC represents the best method to analyze microvascular abnormalities in autoimmune rheumatic diseases .
In addition, capillaroscopic changes have been observed in systemic sclerosis, systemic lupus erythematosus, antiphospholipid syndrome, and Sjogren’s syndrome, but still further epidemiological and clinical studies are needed to better standardize the NC patterns .
| Aim of the work|| |
The aim of this study was to investigate NC abnormalities and serum IL-17 level among RA patients with or without vasculitis.
| Patients and methods|| |
The current study was conducted on 40 RA patients who were diagnosed according to the current 2010 ACR-EULAR criteria for diagnosis of RA.
All patients were subjected to demographic data collection, history taking, clinical examination, calculation of Disease Activity Score (DAS) 28, laboratory measurement [including erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor (RF), anticyclic citrullinated peptide (anti-CCP), antinuclear antibody (ANA), antineutrophil cytoplasmic antibody (ANCA), and IL-17], and NC in which the following capillaroscopic parameters were evaluated using ophthalmoscope: distribution, presence of dilatation, presence of avascular areas, hemorrhages, and neoangiogenesis.
The 40 patients were further divided into two groups: RA patients with NC changes (group 1, n=6) and RA patients with no NC changes (group 2, n=34).
The six patients included in group 1 were further subjected to electrophysiological studies (sural nerve and median nerve).
| Results|| |
The data collected from patients and controls were tabulated and statistically analyzed to study NC abnormalities and serum IL-17 pattern among RA patients with or without vasculitis.
DAS28 showed a significant difference between RA patients with no NC changes (n=34) and RA patients with NC changes (n=6), as shown in [Table 1] and [Figure 1].
|Figure 1: Box plot showing DAS28 range in RA patients with and without NC changes. DAS28, Disease Activity Score 28; NC, nailfold capillaroscopy; RA, rheumatoid arthritis.|
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One RA patient had a mild disease activity (DAS28≤3.2), 20 patients showed a moderate disease activity (DAS28˃3.2 and ≤5.1), and the remaining 19 patients had a severe disease activity (DAS28˃5.10). The six RA patients with vasculitic changes were all found have severe activity (DAS28˃5.1).
There was no significant difference between RA patients with no NC changes (n=34) and RA patients with NC changes (n=6) as regards erythrocyte sedimentation rate and anti-CCP. In contrast, there was a significant difference between those two groups as regards CRP and RF (P<0.01 and 0.10, respectively), as shown in [Table 2] and [Figure 2] and [Figure 3].
|Table 2: The CRP and RF compared between RA patients with NC changes and RA patients with no NC changes|
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|Figure 2: Box plot showing the range of CRP among the two groups, RA patients with NC changes (group 1) and RA patients with no NC changes (group 2). CRP, C-reactive protein; NC, nailfold capillaroscopy; RA, rheumatoid arthritis.|
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|Figure 3: Box plot showing RF among the two groups, RA patients with NC changes (group 1) and RA patients with no NC changes (group 2). NC, nailfold capillaroscopy; RA, rheumatoid arthritis; RF, rheumatoid factor.|
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ANA was compared between RA patients with no NC changes (n=34) and RA patients with NC changes (n=6), and it showed no significant difference ([Table 3]).
|Table 3: Comparing the levels of ANA and ANCA between RA patients with NC changes and RA with no NC changes|
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ANCA showed a significant difference between RA patients with no NC changes (n=34) and RA patients with NC changes (n=6) (P=0.021), as shown in [Table 3] and [Figure 4].
|Figure 4: Bar chart showing the level of ANCA between the two groups, RA with and without NC changes. ANCA, antineutrophil cytoplasmic antibody; NC, nailfold capillaroscopy; RA, rheumatoid arthritis.|
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When IL-17 serum level was compared between RA patients with NC changes (n=6) and RA patients with no NC findings (n=34), a significance difference was found (P<0.001), as shown in [Table 4] and [Figure 5].
|Table 4: Comparing IL-17 diagnostic significance between RA patients with NC changes and RA patients with no NC changes|
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|Figure 5: Box plot representing IL-17 level in RA patients with and without vasculitis. IL-17, interleukin-17; RA, rheumatoid arthritis.|
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| Discussion|| |
The present study included 40 RA patients, of whom only six patients were diagnosed clinically as having RV (15%). This is in agreement with the results of previously published data by Puéchal et al. , which estimated the prevalence of RV at less than 1–5%. Similarly, Loricera et al.  reported a low incidence of RV.
In addition, the current study estimated that the incidence of NC changes is the same as the incidence of vasculitis in the studied patients, which shows that NC changes occur in parallel with clinical vasculitic changes. Similarly, Souza and Kayser  concluded that NC changes were associated with vascular disorders.
In contrast, Hachulla et al.  reported that capillaroscopy when compared between RA patients with and without vasculitis showed no difference.
This study showed a significant difference in DAS28 between RA patients and RV patients, and concluded that patients with higher DAS28 were associated with vasculitic changes. This shows that vasculitis in RA occurs in the disease with high activity as scored with DAS28 in the studied patients.
Similarly, Shanmugan et al.  calculated DAS28 in RA patients before and after the appearance of vasculitic ulcer, and it was concluded that there were a significant rising in DAS28, which implied a significant difference. In contrast, Mederos et al.  concluded that there were discrepancies in data from DAS28 and recommended to define better score with better cutoff.
In the current study, anti-CCP showed no significant difference between RA and RV patients. This implies that anti-CCP is rather a diagnostic than a follow-up tool and its level does not reflect associated vascular abnormalities. In agreement, Wiik et al.  concluded that, although anti-CCP is considered an important marker of progressive erosive disease and extra-articular manifestations such as vasculitis, this was hampered by doubt about a positive versus negative reaction in several assays. Korkmaz et al.  also concluded that anti-CCP did not seem to have much linkage with extra-articular manifestations of RA.
In contrast, Turesson et al.  concluded that anti-CCP levels tend to be higher in patients with RA with vasculitis than in those without vasculitis.
In our study, RF showed a significant difference between RA and RV patients, and it was higher in RV patients (P=0.001). This shows that RF is highly linked and associated with vascular activity.
Similarly, Khasnis and Langford  and Turesson Matterson  concluded that RF level is higher in vasculitis.
In contrast, Tourin et al.  proved that RA-associated vasculitis is associated with low titer-positive RF.
The current study illustrated that there was a significant difference in CRP between RA and RV patients, and CRP was higher in the RV group (P=0.010). This reflects the concluded association between CRP and vasculitic changes. Similarly, Suresh  reported the association of high levels of CRP with RV. Kobak et al.  also showed the significant difference in CRP between RA and RV patients.
However, Šenolt et al.  showed that CRP can be normal in RA with or without extra-articular manifestations.
In the current study, there was no significant difference in ANA between RA and RV patients. This shows that ANA was not associated with vasculitic changes in our studied patients.
In agreement with the findings, Souza et al.  reported that ANA can be negative, with no significant difference in RV. In contrast, Voskuyl et al.  reported that ANA was positive and had significant difference in RV patients.
In the current study, ANCA showed a significant difference in RV patients than in RA patients (P=0.021). This shows that ANCA is associated with vasculitic changes occurring on top of RA in our studied patients.
Similarly, Voskuyl et al.  reported a significant difference in ANCA between RA and RV patients.
In contrast, Puechal et al. (2003)  and Tourin et al. (2013)  excluded the possibility of the presence of significant difference between RA and RV patients.
The current study concluded that there was a significant difference in IL-17 between RV and RA patients, wherein it was more significant in RV patients (P≤0.001). This shows that IL-17 is highly associated with the development of vasculitic changes.
In agreement with the finding, Hoshino et al.  concluded that there was an association between IL-17 and vasculitis. There were no studies that proved otherwise.
Finally, IL-17 and NC changes were confirmed in our study to have a role in RV.
Drawbacks in the current study were as follows: (a) the small sample size of RV patients, and (b) RV patients were diagnosed on the basis of the clinical skin evaluation and laboratory measurements, and no biopsy was done.
| Conclusion|| |
RV is associated with significantly elevated levels of serum IL-17 and characteristic NC changes, which raises their importance in the detection of RV as an extra-articular disease manifestation.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4]