Indian Journal of Dermatology
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Year : 2016  |  Volume : 61  |  Issue : 1  |  Page : 127
Sacral rheumatoid nodule mimicking inflammatory atheroma

Department of Dermatology, Fukushima Medical University, Fukushima, Japan

Date of Web Publication15-Jan-2016

Correspondence Address:
Toshiyuki Yamamoto
Department of Dermatology, Fukushima Medical University, Fukushima
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0019-5154.174199

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How to cite this article:
Kato Y, Yamamoto T. Sacral rheumatoid nodule mimicking inflammatory atheroma. Indian J Dermatol 2016;61:127

How to cite this URL:
Kato Y, Yamamoto T. Sacral rheumatoid nodule mimicking inflammatory atheroma. Indian J Dermatol [serial online] 2016 [cited 2019 Aug 24];61:127. Available from:


A 64-year-old woman visited our hospital complaining of a painful nodule on the buttock. She had been suffering from rheumatoid arthritis (RA) for nearly 15 years, and had been treated with oral methotrexate (8 mg/day), prednisolone (5 mg/day), and subcutaneous injection of etanercept (25 mg/week) for the previous 5 years. She had noted an asymptomatic nodule on the sacral area some years ago, which became painful 2 weeks before presenting at our hospital. Physical examination showed a hen-egg-sized cystic nodule with a reddish surface [Figure 1]a]. Puncture of the nodule revealed necrotic tissue elimination, and bacterial culture was negative. Laboratory examination showed increased rheumatoid factor (695 IU/ml), C-reactive protein (0.25 mg/dl) and matrix metalloproteinase-3 (181 ng/ml, normal: 17.3 ~ 59.7). After inflammation was ceased, a biopsy was carried out which showed large fibrinoid necrosis surrounded by histiocytes as well as lymphocytes [Figure 1]b]. Immunohistochemistry showed that cellular infiltrates around the necrotic tissues were positively stained with CD3, CD68, CD163, and CD204 [Figure 1]c-e]. Furthermore, palisaded histiocytes were reactive for matrix metalloproteinase-1 (MMP-1) and MMP-3 [Figure 1]f and g]. The patient continued to be treated with etanercept, and the nodule gradually flattened 6 months later [Figure 1]h].
Figure 1: (a) Inflammatory cystic nodule on the sacral region. (b) Histological features showing eosinophilic necrosis in the lower dermis to the subcutaneous tissues, with surrounding inflammatory cell infiltrates (H and E stain, x40). Results of immunohistochemistry show strong expression of CD68 (c) as well as CD163 (d) and CD204 (e) palisading cells around the necrotic tissues were immunoreactive for MMP-1 (f) and MMP-3 (g) the nodule flattened after 6 months (h)

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The most interesting feature of this case is the clinical appearance mimicking inflammatory atheroma. Rheumatoid nodule (RN) arising on the sacral area is relatively rare, and only a few cases have been reported, [1],[2],[3] including a case of rheumatoid nodulosis in the sacral region. [3] Recent reports have suggested a paradoxical reaction of new development of RN triggered by treatment targeting TNF-α, [4],[5],[6],[7] however it is unlikely that biologics were relevant to exacerbation of RN in our case, because (i) the sacral nodule existed prior to the use of etanercept, (ii) anti-rheumatic drugs were unchanged, and (iii) treatment with etanercept was continued during the course.

The Koebner phenomenon occasionally plays a role in the development of RN, [8] and repeated mechanical stimuli or some minor trauma may have induced inflammation in our case. Endothelial cell injury may result in local accumulation of IgM immune complexes on the small vessel walls, which subsequently activates monocytes/macrophages. Macrophage-derived proinflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are thought to play a role in the induction of RN. [9] Local secretions of cytokines, mediators, growth factors, proteases, and collagenases lead to inflammation, angiogenesis, necrobiosis, and granuloma formation. Expression of E-selectin is highly detected in the vessels of RN, which suggests active inflammation and cell trafficking into the nodules. Additionally, the cytokine profile of RN includes Th1 cytokines such as interferon-g, IL-1β, TNF-α, IL-12, IL-18, IL-15, and IL-10, suggesting a Th1 granuloma. IL-1β and TNF-α are representative cytokines which upregulate MMP-1 and MMP-3. In our case, MMP-1 and MMP-3 were strongly detected in the histiocytic infiltration surrounding the central necrobiosis, suggesting an important role of proteinases in the necrobiosis of connective tissues of RN. The majority of the palisading cells consist of macrophages that are strongly positive for CD68 and CD204, as well as relatively weak expression of CD163, a surface marker of alternatively activated M2 macrophages. Further studies are required into determining whether the activation of M1- or M2-type macrophages is involved in the development of RN.

   References Top

Sturrock RD, Cowden EA, Howie E, Grennan DM, Watson-Buchanan W. The forgotten nodule: Complications of sacral nodules in rheumatoid arthritis. Br Med J 1975;4:92-3.  Back to cited text no. 1
Kumar A, Sekhar A. Quadriplegia in a case of known rheumatoid arthritis. J Indian Med Assoc 2001;99:226-7.  Back to cited text no. 2
Kai Y, Anzai S, Shibuya H, Fujiwara S, Takayasu S, Asada Y, et al. A case of rheumatoid nodulosis successfully treated with surgery. J Dermatol 2004;31:910-5.  Back to cited text no. 3
Kekow J, Welte T, Kellner U, Pap T. Development of rheumatoid nodules during anti-tumor necrosis factor alpha therapy with etanercept. Arthritis Rheum 2002;46:843-4.  Back to cited text no. 4
Scrivo R, Spadaro A, Iagnocco A, Valesini G. Appearance of rheumatoid nodules following anti-tumor necrosis factor alpha treatment with adalimumab for rheumatoid arthritis. Clin Exp Rheumatol 2007;25:117.  Back to cited text no. 5
Cunnane G, Warnock M, Fye KH, Daikh DI. Accelerated nodulosis and vasculitis following etanercept therapy for rheumatoid arthritis. Arthritis Rheum 2002;47:445-9.  Back to cited text no. 6
Baeten D, De Keyser F, Veys EM, Theate Y, Houssiau FA, Durez P. Tumor necrosis factor alpha independent disease mechanisms in rheumatoid arthritis: A histopathological study on the effect of infliximab on rheumatoid nodules. Ann Rheum Dis 2004;63:489-93.  Back to cited text no. 7
Yamamoto T, Ueki H. Koebner phenomenon in rheumatoid arthritis. J Genet Syndr Gene Ther 2013;4:173.  Back to cited text no. 8
Hessian PA, Highton J, Kean A, Sun CK, Chin M. Cytokine profile of the rheumatoid nodule suggests that it is a Th1 granuloma. Arthritis Rheum 2003;48:334-8.  Back to cited text no. 9


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