Rheumatoid vasculitis, an uncommon extraarticular manifestation
of rheumatoid arthritis, usually develops in long-standing cases
affecting small-to-medium-sized vessels. It is a poor prognostic
marker when multiple systems are affected, skin and neurologic
involvement being most frequent. Rheumatoid vasculitis is seen
more commonly in seropositive and nodular rheumatoid arthritis
patients who are male or smoke. Herein, we present the peculiar
case of a 48-year-old female with rapid onset, progressive, multiple
ulcers predominantly over the flexures. Differential diagnoses of
pyoderma gangrenosum, pyoderma vegetans, pemphigus vegetans,
and vasculitis were considered, and the patient was evaluated. On
investigation, her rheumatoid factor titer was strongly positive;
a skin biopsy revealed leukocytoclastic vasculitis. On clinical,
serological, and histopathological correlation, a diagnosis of
rheumatoid vasculitis was made, responding well to high-dose
prednisolone. On follow-up at six months, her skin lesions had
healed well with moderate scarring; however, she developed
severe joint pain, warranting the initiation of disease-modifying
antirheumatic drugs. To the best of our knowledge, this is a
previously unreported clinical and morphological presentation
of rheumatoid vasculitis.
Rheumatoid vasculitis is a relatively uncommon disease manifestation in patients with rheumatoid arthritis 1 . The morphological pattern can include palpable purpura, nodulo-ulcerative lesions, livedo reticularis, erythema elevatum diutinum, and hemorrhagic bullae. Bannatyne first described vascular involvement in rheumatoid arthritis in 1898 2 . Rheumatoid vasculitis may occur in association with pyoderma gangrenosum, though it can also present alone with ulcerated lesions 3 , 4 . Herein, we present a peculiar case of a 48-year-old female with multiple, rapid-onset, progressive ulcers predominantly over the flexures.
A 48-year-old lady came to our emergency room with a one-week history of multiple, rapid-onset, progressive, somewhat painful, ulcerated lesions, predominantly over the flexures. She had a history of documented low-grade fever associated with these lesions. Mild arthralgia and morning stiffness in the shoulder, wrist, and small joints of the hands were noted on and off for the last three months. The symptoms were mild and sporadic, so the patient did not seek any specific treatment. She was also a known hypertensive and diabetic.
The systemic examination revealed no abnormalities. On mucocutaneous examination, multiple, well-defined, circular-to-elongated ulcers with few smaller satellite lesions were present over the right axilla, bilateral inframammary folds, and bilateral groins (Figure 1 a-c). The margins were punched out, and the floor of the ulcers had adherent yellowish to brown-black crusts (Figure 1 a-c). Similar isolated lesions were seen over the abdomen and thighs. No regional lymphadenopathy was noted, and the mucosae were unremarkable.
Routine & relevant investigations, including a complete blood count (CBC), renal function test (RFT), liver function test (LFT), urine microscopy, chest X-ray (CXR) & electrocardiogram (ECG), were within normal limits. A screening anti-nuclear antibody (ANA) and an anti-neutrophilic cytoplasmic antibody (ANCA) profile were sent and returned negative. However, her rheumatoid arthritis (RA) factor (46.9 IU/ml) was strongly positive, and the erythrocyte sedimentation rate (ESR) was extremely elevated at 120 mm/hr. The pathergy test was negative. A skin biopsy, keeping differential diagnoses of pyoderma gangrenosum, pyoderma vegetans, pemphigus vegetans, and vasculitis, was done after informed consent.
The biopsy revealed epidermal necrosis and ulceration; the dermis had a dense neutrophilic infiltrate in and around the vessel wall. Endothelial cell swelling, leukocytoclasia, and extravasation of red blood cells (RBCs) were present, and fibrinoid necrosis was seen (Figure 2 a-b).
The dermis shows infiltration of the vessel wall by neutrophils with fibrinoid necrosis, leukocytoclasia, endothelial cell swelling, and extravasation of erythrocytes; (a) 100x; (b) 400x
On clinicopathological correlation, a provisional diagnosis of rheumatoid vasculitis was made. She was started on high-dose prednisolone (1 mg/kg/day), showing marked improvement, The steroid dose was gradually tapered over two months, and the lesions healed well with post-inflammatory hyperpigmentation and mild scarring (Figure 3).
On follow-up at six months, she developed severe joint pain restricting her movements, and a rheumatological consult was requested. She subsequently fulfilled the EULAR (European League Against Rheumatism) criteria for rheumatoid arthritis (score=8) and was started on a disease-modifying anti-rheumatoid drug (DMARD). Hence, a final diagnosis of rheumatoid vasculitis was made, where the vasculitic lesions preceded the development of frank rheumatoid arthritis.
Rheumatoid vasculitis is seen in approximately 1-5% of patients with rheumatoid arthritis 5 - 7 . Due to the morphology and rapid onset, our first impression was an atypical pyoderma gangrenosum, even though the lesions were only slightly painful, with minimal tenderness on palpation. However, biopsy findings did not corroborate this. Since pyoderma gangrenosum is a diagnosis of exclusion, we considered other possibilities. Wegener’s granulomatosis, a small vessel vasculitis, has been reported to present with such pyoderma gangrenosum-like lesions in the flexures 8 . However, the ANCA profile was negative, and no granulomas were seen.
Thus, on clinical, serological, and histopathological grounds, we reached a diagnosis of cutaneous-only rheumatoid vasculitis. To the best of our knowledge, such symmetric flexural pyoderma gangrenosum-like lesions have not been previously reported in rheumatoid vasculitis.
Rheumatoid vasculitis usually presents after a mean rheumatoid arthritis disease duration of 13 years, with anecdotal reports of vasculitis preceding or occurring early in rheumatoid arthritis (Table 1). Rheumatoid vasculitis preceding or occurring in early rheumatoid arthritis has been seen as an acute pulmonary syndrome due to vasculitis and even as an acute abdomen in the form of cholecystitis, hepatic artery involvement, and acute bowel perforation . Since rheumatoid vasculitis is usually a systemic vasculitis, an unusual feature in our case was the cutaneous-only pattern.
|No.||Author, year||Age (yrs.) /sex||Features of RV||Associated arthritic features||Temporal relation of RV with RA|
|1.||Parker et al., 2007 9||63/M||1. Mononeuritis multiplex||Symmetrical inflammatory polyarthritis of small joints||RV 7 months after RA diagnosis|
|2. Acute abdomen: abdominal pain, nausea, and vomiting due to small bowel perforation|
|2.||Sandhu et al., 2013 10||74/M||Acute abdomen: periumbilical & right upper quadrant pain; recurrent emesis due to cholecystitis||Symmetrical inflammatory polyarthritis of small joints||RV 1 week after RA diagnosis|
|3.||Tourin et al., 2013 11||61/M||Acute pulmonitis: pleuritic chest pain & dry cough||Symmetric inflammatory polyarthritis of small joints||RV 2 months prior to RA diagnosis|
|4.||Lee et al., 2017 12||72/F||Hepatic artery vasculitis: elevated liver enzymes only, asymptomatic||Symmetric inflammatory polyarthritis of small joints||RV 2 months after RA diagnosis|
|5.||Sacks et al., 2017 13||38/M||Mononeuritis multiplex||Symmetrical inflammatory polyarthritis of small joints||RV 6 years prior to RA diagnosis|
|6.||Anwar et al., 2019 14||44/M||1. Nodulo-ulcerative cutaneous vasculitis||Symmetrical inflammatory polyarthritis of small joints||Concurrent diagnosis of both.|
|Our case||48/F||Cutaneous-only variant with multiple, symmetric, flexural pyoderma gangrenosum-like lesions||Symmetrical inflammatory polyarthritis of small joints||RV 6 months prior to RA diagnosis|
We reported an unprecedented presentation of cutaneous-only rheumatoid vasculitis preceding overt rheumatoid arthritis. Histopathology plays a crucial role in diagnosis; since rheumatological diseases evolve with time, following up on such patients may improve our diagnostic ability and therapeutic interventions.
Conflict of interest
- Saljoughian M. Rheumatoid vasculitis: A complication of rheumatoid arthritis. US Pharm. 2018; 43(6):26-8.
- Makol A, Matteson EL, Warrington KJ. Rheumatoid vasculitis: An update. Curr Opin Rheumatol. 2015; 27(1):63-70.
- Balakrishnan C, Venkatachalam S, Mangat G, et al. Vasculitic ulcers in rheumatoid arthritis. Indian J Dermatol Venereol Leprol. 1994; 60(2):87-88.
- Öien RF, Håkansson A, Hansen BU. Leg ulcers in patients with rheumatoid arthritis—a prospective study of aetiology, wound healing and pain reduction after pinch grafting. Rheumatology. 2001; 40(7):816-20.
- Kaye O, Beckers CC, Paquet P, et al. The frequency of cutaneous vasculitis is not increased in patients with rheumatoid arthritis treated with methotrexate. J Rheumatol. 1996; 23:253-257.
- Salvarani C, Macchioni P, Mantovani W, et al. Extraarticular manifestations of rheumatoid arthritis and HLA antigens in northern Italy. J Rheumatol. 1992; 19:242-246.
- Wattiaux MJ, Kahn MF, Thevenet JP, et al. Vascular involvement in rheumatoid polyarthritis. Retrospective study of 37 cases of rheumatoid polyarthritis with vascular involvement and review of the literature. Ann Med Interne (Paris). 1987; 138:566-587.
- Zarraga MB, Swenson N, Glick B. Pyoderma gangrenosum-associated granulomatosis with polyangitis: a case report and literature review. J Clin Aesth Dermatol. 2017; 10(10):40-2.
- Parker B, Chattopadhyay C. A case of rheumatoid vasculitis involving the gastrointestinal tract in early disease. Rheumatology (Oxford). 2007; 46:1737-8.
- Sandhu SK, Choy G. Vasculitis of the gallbladder in early rheumatoid arthritis. BMJ Case Rep. 2013; 2013:bcr2012008228.
- Tourin O, de la Torre Carazo S, Smith DR, et al. Pulmonary vasculitis as the first manifestation of rheumatoid arthritis. Respir Med Case Rep. 2013; 8:40-2.
- Lee JE, Kim IJ, Cho MS, et al. A case of rheumatoid vasculitis involving hepatic artery in early rheumatoid arthritis. J Korean Med Sci. 2017; 32(7):1207-1210.
- Sacks S, Steuer A. Can rheumatoid vasculitis predate a diagnosis of rheumatoid arthritis?. Eur J Rheumatol. 2017; 4(1):57-8.
- Anwar MM, Tariq EF, Khan U, et al. Rheumatoid vasculitis: Is it always a late manifestation of rheumatoid arthritis?. Cureus. 2019; 11(9):e5790.