A Warm, Tender, and Erythematous Medial Ankle Rash

Correct Answer: A. Deep vein thrombosis

Based on clinical presentation and a low pretest probability, per Wells’ criteria (Table 1), the initial diagnosis for this patient was nonpurulent lower extremity cellulitis (NLEC). Given this diagnosis, oral cephalexin 500 mg every 8 hours was initiated, and the patient was advised to seek medical attention if symptoms persisted or worsened.

After 48 hours of no symptom improvement, additional workup was advised. Doppler ultrasonography revealed a distal deep vein thrombosis (dDVT) in the posterior tibial vein. DDVT specifies thrombosis in the peroneal, anterior, and posterior tibial and muscular veins, and is commonly associated with vascular injury.^1,2 Based on our patient’s presentation and benign history, clinical suspicion for DVT was low, thus resulting in our initial misdiagnosis.

The patient’s score calculated at -2; Low pretest probability: -2 to 0 points, Moderate pretest probability: 1 to 2 points, High pretest probability: 3 to 8 points.³

Differential diagnosis. Without a definitive diagnostic test for nonpurulent cellulitis, about 39% of cases are misdiagnosed as entities such as DVT, dermal hypersensitivity, or lipodermatosclerosis.^4,5 NLEC is two-fold more common than DVT, and more than twelve-fold that of dDVT.⁶ Uncomplicated cellulitis typically resolves with oral antibiotics covering Methicillin-sensitive Staphylococcus aureus and beta-hemolytic streptococci, and generally does not require additional workup.

Tinea incognita (TI), or steroid-modified tinea, is a type of dermatophyte infection associated with improper use of topical or systemic steroids or calcineurin inhibitors.⁷ Depending on location, TI presents similarly to limb tinea, venous insufficiency, drug eruptions, erythema migrans, or eczema.^8,9 Diagnosis is made clinically, but can be confirmed by visualization of long narrow hyphae on KOH skin scrapings, or “moth eaten” skin scales, patchy erythema, dotted vessels, and perifollicular casts on dermoscopy.^8,10

Exercise-induced vasculitis (EIV), also called golfer’s vasculitis, is a benign, self-limiting condition involving the small vessels of the lower legs. EIV typically presents proximal to the medial malleolus in women older than 50 years of age.^11,12 Symptoms include a bilateral or unilateral lower extremity rash with edema, pain, or pruritus during or immediately following strenuous or prolonged activity, especially in the heat.^11,12 Diagnosis is primarily clinical, but further testing with a skin biopsy may reveal leukocytoclastic vasculitis.¹¹

Treatment and management. The standard approach to DVT management involves anticoagulation, primarily with low molecular weight heparin for 5 days, with transition to direct oral anticoagulants (DOAC).^13,14

Management is well-defined for proximal DVT (pDVT); however, treatment guidelines for dDVT remain unclear. A Cochrane study reports benefits of anticoagulation therapy for patients with dDVT without a difference in major bleeding events, although non-major bleeding events increased. However, the small number of participants included in this report highlight the need for additional research.¹⁵ The American Academy of Family Physicians report unclear benefits from anticoagulation in dDVT patients, but other experts recommend DOAC therapy for three months, particularly for idiopathic or unprovoked cases.^16,17

Outcome and follow-up. Upon our patient’s diagnosis of dDVT, antibiotics were discontinued, and subcutaneous enoxaparin was initiated. Due to the unprovoked nature of her dDVT, she was transitioned to a 3-month course of oral apixaban without complications.

Discussion. DVT and NLEC can present with several overlapping clinical features, such as duration of onset, warmth, tenderness, edema, and erythema with poorly demarcated borders. A retrospective study of 542 emergency department visits found that 17% of patients initially suspected to have cellulitis were later diagnosed with DVT.¹⁸ Another study reports 30% to 74% of patients initially treated for cellulitis ultimately received an alternate diagnosis, including DVT.¹⁹ However, literature exploring misdiagnosis rates specifically for dDVT are lacking.

PDVT and dDVT account for 80% and 20% of all lower extremity DVT cases, respectively. DDVT progresses to pulmonary embolism (PE) at a rate of less than 5%, and about 25% of untreated cases can ascend to the proximal leg veins.^20,21,22 In post-surgical patients with untreated pDVT, 50% of cases evolved into a PE within a 3-month timeframe.²³ Therefore, a misdiagnosis of dDVT can be a potentially life-threatening error.

Homan’s sign is a maneuver performed by the clinician to induce traction on the posterior tibial vein, eliciting pain with presence of a thrombus. However, this test is positive in 33% of DVT cases, with 21% false positives.²⁴ Our patient had a falsely negative Homan’s, underscoring the low reliability of this maneuver.

In patients with low pretest probability, a D-dimer assay can further assist in evaluating for DVT.^3,25 Although more sensitive than Homan’s sign, a D-dimer lacks specificity, leading to high rates of false positives, particularly in inflammatory, infectious, or autoimmune processes.^26,27,28 Conversely, compression ultrasonography (CUS) has high specificity (95% to 97.8%) and poor sensitivity (43% to 56.8%) for dDVT, yielding approximately 50% false negatives; while duplex ultrasonography (DUS) offers 94.0% specificity and 71.2% sensitivity.^29,30

Overall, diagnostic decision-making for DVT workup is better defined in patients with moderate to high pretest probability, history of provoking factors, or clinical symptoms specifically in the calf. In contrast, our patient’s presentation was seemingly atypical for DVT, given the location over the medial malleolus, absence of edema, and lack of apparent thromboembolic risk factors. At the time of initial assessment, the patient’s negative Homan’s sign and low-risk Wells’ scoring were sufficient evidence to pursue treatment for NLEC without further diagnostic testing for DVT. Considering the high rate of false positive D-dimer assay levels, additional workup for patients with low-probability of dDVT is vastly at the clinician’s discretion to avoid subjecting patients to time-consuming and costly testing, considering a more likely alternative diagnosis.

It remains imperative, however, to provide patient counseling and maintain high clinical suspicion for an alternative diagnosis in any event where symptoms are unresponsive to initial treatment. Particularly when managing soft tissue infections where misdiagnosis rates are not uncommon, consideration to revisit the differential diagnosis is advisable after 24-72 hours without symptomatic improvement, with 48 hours being the most common recommendation.^4,13,31,32 While this patient experienced a relative delayed diagnosis of her dDVT, the authors take solace in the fact she suffered no adverse consequences due in part to the clinician’s prompt initiation of additional workup following 48 hours of no response to antibiotics.

References

1. Chang JC. Pathogenesis of two faces of dvt: new identity of venous thromboembolism as combined micro-macrothrombosis via unifying mechanism based on "two-path unifying theory" of hemostasis and "two-activation theory of the endothelium". Life (Basel). 2022;12(2):220. doi:10.3390/life12020220
2. Mattos MA, Melendres G, Sumner DS, et al. Prevalence and distribution of calf vein thrombosis in patients with symptomatic deep venous thrombosis: a color-flow duplex study. J Vasc Surg. 1996;24(5):738-744. doi:10.1016/s0741-5214(96)70006-x
3. Modi S, Deisler R, Gozel K, Reicks P, Irwin E, Brunsvold M, Banton K, Beilman GJ. Wells criteria for DVT is a reliable clinical tool to assess the risk of deep venous thrombosis in trauma patients. World J Emerg Surg. 2016;11:24. doi: 10.1186/s13017-016-0078-1.
4. Blumberg G, Long B, Koyfman A. Clinical mimics: an emergency medicine-focused review of cellulitis mimics. J Emerg Med. 2017;53(4):475-484. doi:10.1016/j.jemermed.2017.06.002
5. Cutler TS, Jannat‐Khah DP, Kam B, Mages KC, Evans AT. Prevalence of misdiagnosis of cellulitis: A systematic review and meta‐analysis. J Hosp Med 2022;18(3):254-261. doi:10.1002/jhm.12977
6. Paul J, Czech MM, Balijepally R, et al. Diagnostic and therapeutic challenges of treating opportunistic fungal cellulitis: a case series. BMC Infect Dis. 2022;22:435. https://doi.org/10.1186/s12879-022-07365-8
7. Kim WJ, Kim TW, Mun JH, et al. Tinea incognito in Korea and its risk factors: nine-year multicenter survey. J Korean Med Sci. 2013;28(1):145-151. doi:10.3346/jkms.2013.28.1.145
8. Nowowiejska J, Baran A, Flisiak I. Tinea incognito-a great physician pitfall. J Fungi (Basel). 2022;8(3):312. doi:10.3390/jof8030312
9. Dhaher S. Tinea incognito: Clinical perspectives of a new imitator. Dermatol Reports. 2020;12(1):8323. doi:10.4081/dr.2020.8323
10. Ghaderi A, Tamimi P, Firooz A, Fattahi M, Ghazanfari M, Fattahi M. Updates on tinea incognita: literature review. Curr Med Mycol. 2023;9(2):52-63. doi:10.22034/cmm.2023.345069.1425
11. Jud P, Hafner F. Exercise-induced vasculitis [published correction appears in CMAJ. 2018 Apr 30;190(17 ):E547]. CMAJ. 2018;190(7):E195. doi:10.1503/cmaj.171377
12. Cushman D, Rydberg L. A general rehabilitation inpatient with exercise-induced vasculitis. PM R. 2013;5(10):900-902. doi:10.1016/j.pmrj.2013.04.015
13. Venous thromboembolic diseases: diagnosis, management and thrombophilia testing. London: National Institute for Health and Care Excellence (NICE); 2023 Aug 2. (NICE Clinical Guidelines, No. 158.) Accessed: October 31, 2024. https://www.ncbi.nlm.nih.gov/books/NBK556698/
14. Jones NR, Round T. Venous thromboembolism management and the new NICE guidance: what the busy GP needs to know. Br J Gen Pract. 2021;71(709):379-380. doi: 10.3399/bjgp21X716765. Erratum in: Br J Gen Pract. 2022;72(718):214.
15. Kirkilesis G, Kakkos SK, Bicknell C, Salim S, Kakavia K. Treatment of distal deep vein thrombosis. Cochrane Database Syst Rev. 2020;4(4):CD013422. doi: 10.1002/14651858.CD013422.pub2.
16. Frasca DJ, Leach-Frasca K. Treatment of distal DVT. Am Fam Physician. 2021;103(7):432-433.
17. Stevens SM, Woller SC, Kreuziger LB, et al. Antithrombotic therapy for VTE disease: second update of the CHEST guideline and expert panel report [published correction appears in Chest. 2022 Jul;162(1):269]. Chest. 2021;160(6):e545-e608. doi:10.1016/j.chest.2021.07.055.
18. Rabuka CE, Azoulay LY, Kahn SR. Predictors of a positive duplex scan in patients with a clinical presentation compatible with deep vein thrombosis or cellulitis. Can J Infect Dis. 2003 Jul;14(4):210-4. doi: 10.1155/2003/675682.
19. Williams OM, Hamilton F, Brindle R. The natural history of antibiotic-treated lower limb cellulitis: analysis of data extracted from a multicenter clinical trial. Open Forum Infect Dis. 2023;10(10):ofad488. doi: 10.1093/ofid/ofad488.
20. Robert-Ebadi H, Righini M. Should we diagnose and treat distal deep vein thrombosis? Hematology Am Soc Hematol Educ Program. 2017;2017(1):231-236. doi:10.1182/asheducation-2017.1.231
21. Waheed SM, Kudaravalli P, Hotwagner DT. Deep Vein Thrombosis. 2023 Jan 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29939530
22. Kearon C. Natural history of venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I22-I30. doi:10.1161/01.CIR.0000078464.82671.78
23. Swanson E. Distal deep vein thrombosis causing pulmonary embolism after outpatient plastic surgery: a case report. Plast Reconstr Surg Glob Open. 2020;8(4):e2803. doi:10.1097/GOX.0000000000002803
24. Ambesh P, Obiagwu C, Shetty V. Homan's sign for deep vein thrombosis: A grain of salt?. Indian Heart J. 2017;69(3):418-419. doi:10.1016/j.ihj.2017.01.013
25. Palareti G. How I treat isolated distal deep vein thrombosis (IDDVT). Blood. 2020;123(12):1802-1809. doi: https://doi.org/10.1182/blood-2013-10-512616
26. Ebrahimpour A, Okhovatpour MA, Tabrizi A, Bakhshmandi M. Value of D-dimer as a diagnostic marker of infection associated with orthopedic implants. Adv Biomed Res. 2021;10(1):28. doi:10.4103/abr.abr_277_20
27. Franchini M, Focosi D, Pezzo MP, Mannucci PM. How we manage a high D-dimer. Haematologica. 2024;109(4):1035-1045. doi:10.3324/haematol.2023.283966
28. Kabrhel C, Mark Courtney D, Camargo CA Jr, et al. Factors associated with positive D-dimer results in patients evaluated for pulmonary embolism. Acad Emerg Med. 2010;17(6):589-597. doi:10.1111/j.1553-2712.2010.00765.x
29. Zhang Y, Xia H, Wang Y, et al. The rate of missed diagnosis of lower-limb DVT by ultrasound amounts to 50% or so in patients without symptoms of DVT: A meta-analysis. Medicine (Baltimore). 2019;98(37):e17103. doi: 10.1097/MD.0000000000017103. Erratum in: Medicine (Baltimore). 2019 Dec;98(49):e18469.
30. Goodacre S, Sampson F, Thomas S, van Beek E, Sutton A. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging. 2005;5:6. doi:10.1186/1471-2342-5-6
31. Ihm C, Sutton JD, Timbrook TT, Spivak ES. Treatment duration and associated outcomes for skin and soft tissue infections in patients with obesity or heart failure. Open Forum Infect Dis. 2019;6(6):ofz217. doi:10.1093/ofid/ofz217
32. Brown C, Brandt W, Wang TF, Delluc A, Carrier M. Incidence of recurrent venous thromboembolism and bleeding complications in patients with cancer and isolated distal deep vein thrombosis. Thromb Res. 2023 Aug;228:81-84. doi: 10.1016/j.thromres.2023.05.027.

AUTHORS:
Jessica M. Ruiz-Myara, MS, OMS-IV¹ • Hunter A. Vásquez, MS, OMS-IV¹ • Joy I. Zarandy, DO, FAAFP, DABFM²

AFFILIATIONS:
¹ Philadelphia College of Osteopathic Medicine Georgia, Suwanee, GA
² Department of Family Medicine, Philadelphia College of Osteopathic Medicine Georgia, Suwanee, GA

CITATION:
Ruiz-Myara JM, Vásquez HA, Zarandy JI. A Woman in Her 50s Presents With a Painful Medial Ankle Rash. Consultant. Published online October 31, 2024. doi:10.25270/con.2024.10.000006

Received June 17, 2024. Accepted July 22, 2024

DISCLOSURES:
The authors report no relevant financial relationships.

ACKNOWLEDGMENTS:
None.

CORRESPONDENCE:
Joy Zarandy, DO, Philadelphia College of Osteopathic Medicine (PCOM) – Georgia Campus, 625 Old Peachtree Road NW, Suwanee, GA 30024 (joyza@pcom.edu)

©2024 HMP Global. All Rights Reserved.
Any views and opinions expressed are those of the author(s) and/or participants and do not necessarily reflect the views, policy, or position of Consultant360 or HMP Global, their employees, and affiliates.