When a patient presents with a hot, swollen leg, you may suspect cellulitis—but a critical diagnostic pitfall can lead to needless antibiotic courses and delayed appropriate treatment. A careful history and examination, and consideration of potential differential diagnoses, can improve patient outcomes and prevent unnecessary interventions.

Well versus unwell patients

In your initial assessment, the patient’s general condition provides important clues about the likely diagnosis—with both cellulitis and deep vein thrombosis (DVT) being key differentials.

Be alert to possible pulmonary embolism secondary to DVT, particularly when respiratory symptoms accompany leg swelling. If dyspnoea is present, check blood oxygen saturation.

A patient who presents with unilateral leg swelling and respiratory symptoms after a recent long-haul flight requires urgent Doppler ultrasound or immediate emergency department referral. Patients with fever, tachycardia, or tachypnoea should also be sent to an emergency department.

When patients are systemically well, you can conduct a thorough assessment and consider a broader range of diagnoses.

Beware bilateral cellulitis

Be extremely wary when patients present with bilateral lower limb symptoms. True bilateral cellulitis is very rare, yet hospital discharge summaries sometimes document this diagnosis after excluding DVT/PE.

If it looks like bilateral cellulitis, it’s almost certainly something else. This diagnostic pitfall leads to one of the most common delayed diagnoses in dermatology practice, with patients cycling through multiple antibiotic courses while the underlying condition progresses untreated.

Lipodermatosclerosis masquerading as cellulitis

Lipodermatosclerosis is surprisingly common, typically affecting patients who are overweight with chronic venous insufficiency. In its acute phase, lipodermatosclerosis presents with a hot, red, swollen leg.

The underlying pathophysiology involves incompetent veins causing blood reflux, leading to red blood cell leakage. This results in fibrotic and sclerotic skin changes.

Recognising lipodermatosclerosis

Patients often present with a history of recurrent “cellulitis” episodes. They may have signs of chronic venous insufficiency such as varicose veins or previous venous ulcers, particularly on the medial aspects of the lower legs.

A key diagnostic clue is brownish discoloration (haemosiderin staining) of the lower legs caused by leaked red blood cells. In chronic cases, patients develop the classic “inverted champagne bottle” sign, with enlarged, hardened calves tapering to narrow ankles. The skin develops a leathery, woody texture, often with associated pitting oedema.

Risk factors for venous insufficiency

Obesity plays a significant role, with the weight of the abdominal apron preventing effective venous return to the heart. Previous deep vein thrombosis is another risk factor, as it can damage venous valves and lead to chronic insufficiency. People who work in occupations that involve standing for extended periods are also at increased risk.

Compression therapy and specialist referral are warranted in patients with venous disease who develop pain at rest, or pain accompanied by recurrent lower limb swelling.

Investigations and differential diagnosis tips

Skin swabs aren’t particularly useful in diagnosing cellulitis unless there’s obvious skin breakdown with purulent or serous discharge, as they typically yield commensal organisms rather than pathogenic bacteria. The diagnosis of cellulitis remains primarily clinical.

Doppler ultrasound studies can identify venous reflux and guide treatment decisions for suspected venous insufficiency.

Most patients who develop true cellulitis have predisposing factors, such as diabetes, peripheral vascular disease or immunosuppression. They may present with systemic toxicity symptoms including fever, tachycardia, and malaise.

Consider lipodermatosclerosis when patients have recurrent bilateral episodes, obvious venous insufficiency signs, or haemosiderin staining. History is often the key—repeated episodes of presumed cellulitis that fail to resolve completely should trigger reconsideration of the diagnosis.

Managing confirmed cellulitis

When lower limb cellulitis is confirmed, oral antibiotics targeting gram-positive organisms remain the mainstay of treatment. Flucloxacillin and cephalexin are generally recommended, with clindamycin an alternative agent for penicillin-allergic patients.

Treating lipodermatosclerosis

Lipodermatosclerosis management requires a different approach. It’s important to include mid-potency topical corticosteroids in your treatment strategy to reduce inflammation. If you have any concerns about using topical steroids in the context of possible cellulitis, check in with a dermatologist or vascular surgeon. Elevating the legs can help, as can compression stockings and regular moisturising.

When to refer

Referral to a dermatologist or vascular specialist is recommended in patients with:

• Active venous ulcers
• Suspected or confirmed lipodermatosclerosis if systemic therapies such as pentoxifylline (which reduces blood viscosity and improves red blood cell flexibility) are being considered.

Key takeaways

• Assess unwell patients for DVT/PE; refer for urgent Doppler or ED assessment if systemic signs or respiratory symptoms are present.
• Bilateral lower limb cellulitis is rare and should prompt consideration of alternative diagnoses, particularly lipodermatosclerosis.
• Signs that suggest lipodermatosclerosis include haemosiderin staining, woody skin, and inverted champagne bottle legs.
• Refer to dermatology/vascular if patients have active venous ulcers or requite systemic treatment for suspected lipodermatosclerosis.

Dr Philip Tong is a Sydney-based dermatologist and founder of DermScreen, a telehealth platform that supports GPs with dermatology-related clinical decision making. He offers nation-wide telehealth services for medical dermatology including acne, eczema and psoriasis through his clinic Dermatology Junction.