Cellulitis differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Aditya Govindavarjhulla, M.B.B.S.

Overview

Cellulitis should be distinguished from thrombophlebitis, contact dermatitis, insect stings, drug reactions, and arthritis.

Differentiating Cellulitis from other Diseases

Cellulitis must be differentiated from other causes of lower limb edema like chronic venous insufficiency, acute deep venous thrombosis, lipedema, myxedema, lymphatic filariasis and causes of generalized edema.

Diseases	Symptoms							Signs	Gold standard Investigation to diagnose
	History	Onset	Pain	Fever	Laterality	Scrotal swelling	Symptoms of primary disease
(Cellulitis-erysipelas-skin abscess)	Acute painful swelling Fever	Acute	+	+	Unilateral	-	-	Tenderness, hotness, and may be fluctuation if abscess formed. Lymphangitis in nearby lymph nodes. Toxemia and fever in severe cases. Cellulitis involves the deeper dermis and erysipelas involves the upper dermis.	Usually it doesn't need any laboratory tests to diagnose. Blood cultures are warranted for patients in the following circumstances: Systemic toxicity Extensive skin or soft tissue involvement Underlying comorbidities persistent cellulitis In patients with recurrent cellulitis, serologic testing for beta-hemolytic streptococci is a good diagnostic tool.
Lymphatic filariasis	History of living in endemic area or travelling to it	Chronic	+	+	Bilateral	+	-	Hepatomegaly Lymphedema Elephantiasis Lymphangitis Hydrocele Scrotal elephantiasis Lymphadenopathies Rhonchi may be present in patients with Pulmonary tropical eosinophilia syndrome.	Preparing blood smears Thick smears Thick smears consist of a thick layer of dehemoglobinized (lysed) red blood cells (RBCs). Thick smears allow a more efficient detection of parasites (increased sensitivity). Thin smears consist of blood spread in a layer such that the thickness decrease. By the ultrasound, the following findings can be observed: Dilated lymphatic channels Living worms tend to be in motion which called "filarial dance" sign.
Chronic venous insufficiency	History of untreated varicose veins Painful bilateral lower limb swelling that increases with standing and decreases by rest and leg elevation.	Chronic	+	-	Bilateral	+ (If congenial)	-	Typical varicose veins Skin change distribution correlate with varicose veins sites in the medial side of ankle and leg Reduction of swelling with limb elevation.	Duplex ultrasound will demonstrate typical findings of venous valvular insufficiency
Acute deep venous thrombosis	History of prolonged recumbency Classic symptoms of DVT include acute unilateral swelling, pain, and erythema	Acute	+	-	Unilateral	-	May be associated with primary disease mandates recumbency for long duration	Dilated superficial veins Difference in calf diameter is twice as likely to have DVT(most impotant sign ) Calf pain on passive dorsiflexion of the foot (Homan's sign) isn't realiable sign.	Compression ultrasonography (CUS) with doppler is the diagnostic test of choice D-dimer level is used for unprobable cases
Lipedema	Family history especially in women; X-linked dominant or autosomal dominant condition. Abnormal deposition of fat and edema and easy bruising.	Chronic	+	-	Bilateral	-	-	Tender with palpation Negative Semmer sign to differentiate from lymphedema. Pinching the skin on the upper surface of the toes. If it is possible to grasp a thin fold of tissue then it is negative result. In a positive result, it is only possible to grasp a lump of tissue.	MRI offers strong qualitative and quantitative parameters in the diagnosis of lipedema
Myxedema	History of untreated hypothyroidism. Infiltration of the skin with glycosaminoglycans with associated water retention.	Chronic	+	-	Bilateral	-	+ (hypothyroidism )	Pretibial myxedema	Thyroid function tests.
Other causes of generalized edema	History of chronic general condition (cardiac-liver-renal)	Chronic	-	-	Bilateral	-	+		According to the primary cause ( Echo- LFTs- RFT)

Cellulitis can be promptly diagnosed with an appropriate history and physical exam. Administration of an antibiotic therapy will initiate resolution of the condition in 2-3 days. Differentials have to be thought of only when resolution is not seen. Non- resolution of cellulitis can be due to infection by resistant strains of the bacterium involved.

There are many dermatological conditions which manifest in manner similar to cellulitis. Careful evaluation of each case, based on accurate history and physical examinations, is very important. Differentials are as follows:

• Erysipelas is a skin infection similar to cellulitis, but it affects superficial layers of the skin. It has more demarcated edges than cellulitis.

• Erysipeloid is a skin infection which is mostly occupational in nature. It is most commonly seen in people involved in the poultry and meat industry. It is characterized by local lesions, diffuse lesions and systemic forms.

• Deep vein thrombosis is a condition in which a blood clot is formed in the deep veins. It can be differentiated from cellulitis by the presence of tenderness along the clotted vein. Duplex ultrasonography would reveal the clot in the vein.

• Necrotizing fasciitis looks like cellulitis at the onset of the disease but it is much more serious. Large amounts of pain, necrosis, and bullae are noticeable. It often requires surgical exploration.

There are a few conditions which can be misdiagnosed as cellulitis such as thrombophlebitis, contact dermatitis, insect stings, drug reactions, arthritis.

• Contact dermatitis is an inflammation of the skin in response to direct exposure to an allergic or irritating substance. This inflammation is usually present with papular erythematous indistinct margins. The extent of distribution is often limited to the area of exposure.

• Insect bites cause a local reaction leading to the development of erythema, tenderness, pruritus and edema. In severe reactions, it can involve adjacent joints. In very severe cases, insect bites can lead to anaphylaxis.

• Drug rashes are the cutaneous presentation of a drug reaction. The rashes are variable, ranging from a pinkish hue to an exanthem. The rash can be limited or widespread. Itching is the most common symptom. If fever, dehydration and involvement of membranous surfaces is present along with the rash, then other diagnoses have to be considered. Drug rashes present most commonly when taking drugs such as sulfa, anticonvulsant drugs, and insulin from animal sources.

• Arthritis presents as pain in the joints, but at times it can be severe enough to present as erythema. At times, septic arthritis can infect overlying skin and can cause cellulitis.

• Some autoimmune conditions may mimic symptoms of or actually cause cellulitis. Panniculitis, Familial Mediterranean Fever, and Hyper IgD syndrome can present erythema and other systemic symptoms.

• In leukemic patients, some times cancerous cells infiltrate the skin causing erythema, papules, and nodules. The cause of these symptoms has to be differentiated by immunostaining.

Cellulitis must be differentiated from other diseases that cause bone pain, edema, and erythema.

Disease	Findings
Soft tissue infection (Commonly cellulitis)	History of skin warmness, swelling and erythema. Bone probing is the definite way to differentiate them.
Osteonecrosis (Avascular necrosis of bone)	Previous history of trauma, radiation, use of steroids or biphosphonates are suggestive to differentiate osteonecrosis from ostemyelitis. MRI is diagnostic.
Charcot joint	Patients with Charcot joint commonly develop skin ulcerations that can in turn lead to secondary osteomyelitis. Contrast-enhanced MRI may be diagnostically useful if it shows a sinus tract, replacement of soft tissue fat, a fluid collection, or extensive marrow abnormalities. Bone biopsy is the definitive diagnostic modality.
Bone tumors	May present with local pain and radiographic changes consistent with osteomyelitis. Tumors most likely to mimic osteomyelitis are osteoid osteomas and chondroblastomas that produce small, round, radiolucent lesions on radiographs.
Gout	Gout presents with joint pain and swelling. Joint aspiration and crystals in synovial fluid is diagnostic for gout.
SAPHO syndrome (Synovitis, acne, pustulosis, hyperostosis, and osteitis)	SAPHO syndrome consists of a wide spectrum of neutrophilic dermatosis associated with aseptic osteoarticular lesions. It can mimic osteomyelitis in patients who lack the characteristic findings of pustulosis and synovitis. The diagnosis is established via clinical manifestations; bone culture is sterile in the setting of osteitis.
Sarcoidosis	It involves most frequently the pulmonary parenchyma and mediastinal lymph nodes, but any organ system can be affected. Bone involvement is often bilateral and bones commonly affected include the middle and distal phalanges (producing “sausage finger”), wrist, skull, vertebral column, and long bones.
Langerhans' cell histiocytosis	The disease usually manifests in the skeleton and solitary bone lesions are encountered twice as often as multiple bone lesions. The tumours can develop in any bone, but most commonly originate in the skull and jaw, followed by vertebral bodies, ribs, pelvis, and long bones.