Diagnosis and Treatment of Cellulitis: Why Can't We Get It Right?

Roni K. Devlin, MD, MBS


February 09, 2022

I can honestly say that not a week goes by on the infectious diseases service without at least one consult request for cellulitis (and often, there are multiple cases). This has always surprised me — cellulitis is a disease that all hospital-based physicians have studied, diagnosed, managed, and cured. Why would an infectious diseases expert need to weigh in, too?

I'm not the only physician that has noticed this trend, either. One recent study, conducted by researchers at Brigham and Women's Hospital and Harvard Medical School, examined data for 259 patients admitted with an initial diagnosis of cellulitis. Nearly a third of these patients were considered to have been misdiagnosed, and a good portion would not have required either antibiotic use or hospital admission if they had been diagnosed correctly. I'd estimate that about half of my consults for cellulitis result in a diagnosis of pseudocellulitis (similar exam findings of skin redness, swelling, and pain, but due to a noninfectious etiology).

Uncomplicated cellulitis, as a disease process, hasn't changed much since we learned about it in medical school and residency. It is still caused by unilateral entry of bacteria through a break in the skin (whether appreciated by the naked eye or not), and it most often involves one of the lower extremities. Most cases are due to beta-strep organisms (usually group A, B, C, or G), resulting in inflammation of the skin and underlying layers. Cellulitis is often accompanied by an immune response causing fever, rigors, sweats, myalgias, and/or malaise; these systemic symptoms can manifest before or after the skin changes are appreciated.

The diagnosis of cellulitis can usually be made by history and physical without laboratory assessment. Beta-strep organisms are highly sensitive to beta-lactam antibiotics (including penicillin), yet many patients admitted with presumed cellulitis are started on multiple broad-spectrum agents (and yes, I have seen vancomycin plus meropenem used inappropriately on many occasions for this diagnosis).

The request for ID consultation often comes 2-3 days into a patient's hospital stay. By then, if the patient has confirmed cellulitis, they have already demonstrated good response to antibiotic use: no further fever or rigors, improved white blood cell count, and less pain. I can usually transition them immediately to oral antibiotics for a short course (uncomplicated cellulitis requires only 5 days of antibiotics).

At least half the time, though, I instead make the diagnosis of pseudocellulitis, which may be due to insect bite, contact or stasis dermatitis, drug reaction or vasculitis, lymphedema with stretch or dependent erythema, panniculitis, gout, or deep venous thrombosis. So, my time is spent documenting all the reasons why I think a patient doesn't have cellulitis; in these cases, I suggest that antibiotics be stopped and that the primary service reconsider the differential diagnosis and management plan.

How can we do better in diagnosing and treating cellulitis for our patients? Here's what I'd suggest.

1. Get a good story.

Often, the history alone can help distinguish between cellulitis and pseudocellulitis. Both legs involved? Not likely cellulitis. Symptoms progressive over days to weeks? Not likely cellulitis. No systemic symptoms despite acute onset? Not likely cellulitis.

2. Do a thorough exam.

Cellulitis is usually unilateral. The involved skin is most often diffusely red, swollen, and painful (though some patients have purplish discoloration or superficial hemorrhage); it is hot to the touch. Enlargement of regional lymph nodes can also be palpated.

3. Remember that skin findings change with time.

I sometimes liken the skin findings of cellulitis to a burn injury. The inflamed skin can seem thickened, and swelling of the hair follicles can cause dimpling (known as "peau d'orange"). The superficial skin layers sometimes separate, which can lead to blistering or collections of fluid under the surface. Blisters may pop and skin can peel. And damaged skin doesn't immediately return to normal, even as the infection is cured. Some patients (such as those with underlying skin conditions, chronic hyperpigmentation, and lymphedema) are left with residual discoloration that can be particularly apparent with increased swelling or gravity influence.

4. Match your bugs and drugs.

Since most cases of uncomplicated cellulitis are due to beta-strep organisms, there is usually no need for multiple broad-spectrum antibiotics. I typically recommend cefazolin, with a transition to either amoxicillin or cephalexin once the patient demonstrates overall clinical improvement. Remember, the skin appearance can worsen after antibiotics — this shouldn't be interpreted as a treatment failure, especially if all other clinical measures show an appropriate response.

5. Shorten your antibiotic duration.

For patients that respond rapidly to antibiotics, a 5-day course is sufficient. Patients who are immunocompromised or slow to respond to treatment may need 10 days.

6. Don't make things worse.

Inflamed skin can be irritated by progressive edema or stretching, use of soaps or moisturizers with dyes or fragrances, topical ointments or creams, influence of gravity, and/or dressings that hold moisture in place.

Of course, I realize that the diagnosis and management of cellulitis can be complicated by abscess formation or an underlying concern for osteomyelitis, and on rare occasion, you'll see a case caused by a pathogen other than beta-strep. But we all need to do better in the diagnosis and treatment of this infection. I hold on to the hope that someday when I'm on the inpatient ID service, I won't be asked to consult for cellulitis at all.

Comments to this blog post are welcomed and encouraged. If you have an infectious disease topic you'd be interested in reading about here, please don't hesitate to mention it.

Join Medscape's new blog initiative! We're looking for physicians, nurses, PAs, specialists, and other healthcare professionals who are willing to share their expertise in one to two paid blog posts per month. Please email for more information.

Follow Medscape on Facebook, Twitter, Instagram, and YouTube

About Dr Roni Devlin
Roni K. Devlin, MD, MBS, is an infectious diseases physician currently residing in the Midwest. She is the author of several scholarly papers and two books on influenza. With a longstanding interest in reading and writing beyond the world of medicine, she has also owned an independent bookstore, founded a literary nonprofit, and published articles and book reviews for various online and print publications. You can reach her via LinkedIn.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.