Introduction
Cellulitis is a common bacterial skin infection, typically presenting as a poorly demarcated, warm, erythematous area with associated oedema and tenderness to palpation. Diagnosis of cellulitis is mainly clinical. 1 It is not uncommon to misdiagnose non-infectious cause of skin inflammation as cellulitis. 2,3,4 This case echoes the sentiment of misdiagnosis of cellulitis and highlights the importance of considering the cellulitis mimics.
Case Description
Presentation
An 83-year-old female with a past medical history of essential hypertension presented to the same day emergency clinic (SDEC) for recently worsening pain in the right leg on a background of ongoing bilateral leg swelling over the last 3 weeks. She had previously been well, with independent mobility and daily activities. She had already received a 2-week course of antibiotics prescribed by the GP. Despite this, there was no clinical improvement and the right leg became increasingly painful, affecting her sleep and mobility.
Clinical examination revealed bilateral pitting leg oedema with erythema and increased localised temperature over the right leg from the ankle up to the upper thigh.
Initial investigations
CRP was 105 milligram/litre while the white cells were normal at 8.7 x109 per L.
Blood tests showed AKI stage II with creatinine of 153 micromoles/l while baseline creatinine was around 60 micromoles/L. Urea was 17.8 mmol/l. Albumin was slightly low at 32 g/l. NT pro BNP was raised at 634 ng/l. There was evidence of normocytic anaemia with Hb 112 g/l. Other blood tests including platelet count, electrolytes, liver enzymes and thyroid function tests were within the reference range. Urinalysis was done to look for any significant proteinuria and it showed only trace of protein.
An Ultrasound with Doppler for the right leg swelling showed no evidence of deep vein thrombosis (DVT).
Initial diagnosis and treatment
The impression on admission was bilateral cellulitis and acute kidney injury (AKI) stage II likely pre-renal, precipitated by infection. IV flucloxacillin was commenced to cover for bilateral cellulitis as per the local microbiology guidelines.
Progress
Despite 5 days of IV flucloxacillin, leg oedema persisted, and CRP remained elevated in the absence of fever. In view of persistently high CRP, IV flucloxacillin was switched to IV vancomycin.
An ultrasound of the kidneys was done to investigate the acute kidney injury. It revealed incidental finding of ascites. Ongoing leg swellings with ascites prompted the consideration of other clinical conditions like fluid overload and possible undiagnosed pelvic malignancy compressing venous drainage leading to bilateral leg swellings. Tumour markers including CA125 were sent, and ultrasound pelvis and CT chest abdomen and pelvis were requested. Diagnostic ascites tap was performed. CA125 returned at a level of 1188 kunits/l. The ascites fluid cytology showed evidence of adenocarcinoma.
Trans-vaginal ultrasound showed a distended endometrial cavity with possible thickened endometrium. Subsequent CT scan showed pathological endometrial cavity dilatation with large volume ascites and widespread peritoneal disease. There was also right long saphenous vein superficial thrombophlebitis extending to adjacent saphenofemoral junction and there was no visible deep vein thrombosis.
Final diagnosis
Based on these results, it was concluded that the rising CRP is more likely related to ongoing malignancy process rather than infection. After discussion with the microbiologist, antibiotics were discontinued with plan to repeat septic screen and monitor for any flare of infection. She was also started on anticoagulation in view of extended superficial thrombophlebitis. There was no clinical evidence of sepsis during the monitoring period for 2 days. The final diagnosis at discharge was newly diagnosed gynaecological malignancy with peritoneal metastasis resulting in ascites and extended right superficial thrombophlebitis. She was discharged from the hospital with the plan for review at the gynaecology multidisciplinary follow-up for management of new diagnosis of gynaecology malignancy.
Discussion
Cellulitis is a relatively common medical condition, with an incidence of approximately 50 cases per 1000 patient-years globally.1 Despite the common prevalence of cellulitis, the diagnostic challenge remains with the lack of globally agreed diagnostic criteria and the presence of many mimicking clinical conditions. It is frequently misdiagnosed, with approximately 30% of cases initially mistaken for cellulitis.2,3,4
In our case, the presentation of increasing pain with temperature and erythema over the right leg with high CRP on a background of 3-week history of new bilateral leg swellings prompted the initial diagnosis of bilateral cellulitis. However, a salient point to note is that bilateral lower leg cellulitis is very rare in the absence of specific risk factors like skin trauma or underlying co-morbidities 5. It is important to consider other cellulitis mimics like venous stasis dermatitis, lymphedema, deep vein thrombosis, gout and contact dermatitis. 2
The patient in this case did not have any skin trauma or any previous medical history or clinical feature to suggest chronic venous stasis or lymphoedema. The initial ultrasound doppler of right leg did not show any evidence of deep vein thrombosis or superficial thrombophlebitis. Other common causes for bilateral leg swellings like cardiac failure, hypoalbuminemia, and thyroid dysfunction were explored but there was no clear evidence to suggest these conditions.
Given the lack of response to the antibiotic therapy with persistent swelling and high CRP, further investigations were conducted to explore less common condition like venous compression caused by pelvic malignancy. In this particular case, CT abdomen and pelvis scan and ascites cytology confirmed the underlying cause of adenocarcinoma of uterus with peritoneal metastases and right superficial thrombophlebitis extending to saphenofemoral junction, explaining the symptoms of bilateral asynchronous leg swellings, predominantly affecting the right leg.
Retrospective speculation of this case suggested that the pelvic malignancy and peritoneal metastases may have caused venous stasis leading to bilateral leg swelling over the course of several weeks and right superficial thrombophlebitis is likely responsible for the acute onset of worsening pain in the right leg. The initial negative DVT scan might have missed the finding of superficial thrombophlebitis. This emphasised the inter-operator variability with ultrasounds imaging and the need to repeat the imaging or use alternatives if there is discrepancy between the imaging report and the clinical suspicion.
This case highlighted that it is crucial to reconsider the diagnosis when the clinical progression does not align with the expected outcome. It is important to have a broad differentials and avoid premature diagnostic closure, especially when the initial diagnosis is very rare like bilateral lower leg cellulitis. In such case of bilateral painful leg swellings, CT scanning of the abdomen and pelvis should be considered after ruling out common causes of bilateral leg swelling. 6
Conclusion
Bilateral cellulitis is very rare, and a broad differential diagnosis should be considered, especially in the absence of risk factors like skin trauma or significant co-morbidities. Imaging of the pelvis and abdomen should be considered when the cause of bilateral leg swelling remains unclear after initial clinical assessment and investigation.
Reference
1. Brown BD, Hood Watson KL. Cellulitis. [Updated 2023 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK549770/
2. Weng QY, Raff AB, Cohen JM, et al. Costs and consequences associated with misdiagnosed lower extremity cellulitis. JAMA Dermatol. 2017;153(2):141–146. doi: 10.1001/jamadermatol.2016.3816.
3. David CV, Chira S, Eells SJ, Ladrigan M, Papier A, Miller LG, Craft N. Diagnostic accuracy in patients admitted to hospitals with cellulitis. Dermatol Online J. 2011 Mar 15;17(3):1. PMID: 21426867.
4. Ko LN, Garza-Mayers AC, St John J, Strazzula L, Vedak P, Shah R, Dobry AS, Rao SR, Milne LW, Parry BA, Kroshinsky D. Effect of dermatology consultation on outcomes for patients with presumed cellulitis: A randomized clinical trial. JAMA Dermatol. 2018 May 1;154(5):529-536. doi: 10.1001/jamadermatol.2017.6196. PMID: 29453872; PMCID: PMC5876891.
5. Chuang YC, Liu PY, Lai KL, Tseng CH. Bilateral lower limbs cellulitis: A narrative review of an overlooked clinical dilemma. Int J Gen Med. 2022 Jun 9;15:5567-5578. doi: 10.2147/IJGM.S356852. PMID: 35707739; PMCID: PMC9191579.
6.Goodkin DA. Massive adrenocortical carcinoma presenting as peripheral edema: a case report. J Med Case Rep. 2022 Jun 20;16(1):249. doi: 10.1186/s13256-022-03397-5. PMID: 35725572; PMCID: PMC9210600.
Author Information
Inzali Moe Moe Kyaw
MBBS, MRCP (UK), MRCP (Acute Medicine),
PGCert Clin Ed Consultant in Acute Medicine
Department of Acute Internal Medicine, West Suffolk Hospital, UK
