Atypical Presentation of Rheumatoid Arthritis with Erythema Nodosum Mimicking Cellulitis: A Case Report

by Laxman Wagle1*, Parmartha Basnyat1, Anuj Timshina2, Rashmita Regmi3

1Department of Internal Medicine, Ascension Saint Agnes Hospital, Maryland, USA

2Department of Internal Medicine, Patan Academy of Health Science, Kathmandu, Nepal

3Department of Nursing, Karnali Academy of Health Science, Jumla, Nepal

*Corresponding author: Laxman Wagle, Department of Internal Medicine, Ascension Saint Agnes Hospital, Maryland, USA

Received Date: 16 March 2024

Accepted Date: 21 March 2024

Published Date: 25 March 2024

Citation: Wagle L, Basnyat P, Timshina A, Regmi R (2024) Atypical Presentation of Rheumatoid Arthritis with Erythema Nodosum Mimicking Cellulitis: A Case Report. Ann Case Report. 9: 1714.


Erythema nodosum (EN) is a septal panniculitis that can have several etiologies. We report a case of a 35-yearold female with recurrent fever and a painful rash on the right thigh. A skin biopsy revealed septal panniculitis and Miescher’s granuloma, suggestive of EN. Since these histopathological changes are nonspecific, extensive workup was done to find out the causes of erythema nodosum, considering infectious, autoimmune, and malignant etiologies. She was found to have high rheumatoid factor and an anti-cyclic citrullinated peptide antibody, which was strongly positive and suggestive of rheumatoid arthritis. Her symptoms were resolved with steroids. It can be challenging to find out the etiology of erythema nodosum or make a diagnosis of rheumatoid arthritis when a patient presents solely with extra-articular manifestations.

Keywords: Rheumatoid Arthritis; Erythema Nodosum; Anti-Cyclic Citrullinated Peptide Antibody; Miescher’s Granuloma; Steroid Therapy.


Rheumatoid arthritis (RA) is a chronic inflammatory systemic disease, among many others, including systemic lupus erythematosus that can involve multiple system organs and present with diverse clinical features [1]. As per the Global

Burden of Diseases, Injuries, and Risk Factors 2017 study, the age-standardized point prevalence of RA was 246.6 (95% UI 222.4 to 270.8) [2]. Similarly, it is also one of the major contributors to global disability [3]. Rheumatoid arthritis develops as a result of genetic predispositions, environmental triggers, and immunological factors, which together lead to synovial immunological response, inflammation, and joint damage [4]. Typically RA manifests with involvement of multiple joints but can also have atypical or extra-articular involvement including skin (rheumatoid nodules), heart, lungs (interstitial lung disease), cardiac (pericardial effusion), anemia, Felty syndrome, amyloidosis, carpal tunnel syndrome, scleritis, and many others.

These extra-articular manifestations are seen in 17.8-40.9% of the patients with RA [5]. It can have various cutaneous lesions ranging from rheumatoid nodules to vasculitis and dermatitis [6]. Cutaneous lesions are common but mostly present with symmetric arthritis [7]. Erythema nodosum (EN) is a septal panniculitis that results from a reactive process to various etiologies, such as inflammation, infections, neoplasms, and medications. Very few cases of EN have been reported in patients with RA. Streptococcal infection, primary tuberculosis, sarcoidosis, Behçet’s disease, medication, inflammatory bowel disease, non-Hodgkin lymphoma, and pregnancy were reported as common causes of EN but no etiology was identified in several cases [8-14]. EN presents as painful and erythematous nodules in the subcutaneous tissue usually seen on the shins. Histologically, it reveals septal panniculitis without vasculitis with early lesions showing lymphohistiocytic infiltrate along with neutrophils and eosinophils in the septae and surrounding adipose tissue [14]. Miescher’s radial granuloma is characteristic of EN, consisting of small histiocytes surrounding a central cleft [15].

Case Presentation

We present a case of a 35-year-old Hispanic female with no significant past medical history who presented to the emergency room with complaints of recurrent episodes of fever, swelling, rash, and pain in her right thigh that had been going on for almost 2 months. She presented to the hospital for similar problems three times, when she was empirically treated for cellulitis each time with IV antibiotics initially during the hospital stay and was discharged on oral antibiotics. The blood culture was negative during each visit. She continued to have these symptoms persistently and again presented for the fourth time with fever, swelling, and pain in the upper inner aspect of her right thigh. These symptoms were associated with dizziness and a painful nodular rash on both thighs and shins. She denied taking any medications, having a family history of autoimmune diseases or cancer, or having a personal history of smoking, alcohol, or illicit drug use. Upon initial assessment, she was tachycardic with a pulse rate of 120 per minute, a blood pressure of 95/57 mm of Hg, a temperature of 38.5 degrees Celsius, a respiratory rate of 20 breaths per minute, and a pulse oximetry reading of 98% on room air. She had also lost 5 pounds in the last 3 months. Clinical examination showed significant induration, mild tenderness, and redness in the medial aspect of the right thigh. There were multiple nodular lesions on both legs that were tender on palpation (see figure 1). Both ankles had slight swelling, tenderness to touch, and a limited range of motion.

Since she exhibited features of systemic inflammatory response syndrome (SIRS), initially thought to be secondary to cellulitis, she was started on broad-spectrum antibiotics. She had experienced two spikes of fever in the first two days of admission. Despite not having leukocytosis and her recurrent admission for similar symptoms with no response to antibiotics, further workup was done. A skin biopsy was done, which showed septal panniculitis, and histiocytic collection demonstrating intercellular clefting, suggestive of Miescher granuloma (see histopathological Figures 2-4). No evidence of vasculitis or atypia was found, and the spirochete stain was negative. AFB (Acid Fast Bacilli) stain failed to highlight acid-fast bacilli and fungal hyphae, respectively. Acknowledging histologic changes are nonspecific, extensive workup was done for erythema nodosum, considering infectious, autoimmune, and malignant etiologies. Serologies for bacterial, mycobacterial, hepatitis profile, HIV, and fungal infections, including Aspergillus, Histoplasma, and Coccidioides, were sent, all of which returned negative. Antibody panel evaluations for autoimmune conditions revealed negative results for ANA, c-ANCA, p-ANCA, SSA, SSB, anti-double-stranded DNA, and anti-Smith antibodies. Anti-streptolysin O antibody screens, C3-C4 levels, and total complement were also within normal ranges. Computed tomography of the chest did not show hilar or mediastinal lymphadenopathy. The transthoracic echocardiogram showed no evidence of vegetation. Colonoscopy with a random biopsy of the colonic mucosa revealed normal mucosa with no signs of inflammation, polyps, masses, or ulcers. However, the rheumatoid factor was elevated at 128 and the cyclic citrullinated peptide (CCP) antibody test revealed a strongly positive result of 80. These findings were suggestive of rheumatoid arthritis. Given the diagnosis of erythema nodosum secondary to rheumatoid arthritis, the patient was started on prednisone at a dose of 1 mg per kg for the first 7 days. Following the initiation of steroids, her symptoms improved with the resolution of fever and tachycardia in 48-72 hours. Further investigations were conducted to assess the systemic involvement of rheumatoid diseases. The bilateral ankle and hand x-rays showed no signs of fractures, dislocations, or soft tissue inflammation. Prednisone was then planned to be tapered by 10 mg per week, consecutively. After gradual improvement and absence of other systemic signs and symptoms, the patient was discharged home with a tapering dose of steroid and trimethoprim/sulfamethoxazole for Pneumocystis jirovecii pneumonia prophylaxis. The patient followed rheumatology on an outpatient basis with improvement in rash and was started on maintenance prednisone 20 mg once a day.


Figure 1: Erythema nodosum of bilateral thigh.