Sweet’s Syndrome and Erythema Nodosum: What is the Difference?

Erythema nodosum is a skin condition where red lumps (lesions) mainly form on the shins. It is a type of panniculitis, i.e. an inflammatory disorder affecting the fatty tissue under the skin. It is a condition that is sometimes confused with Sweet’s syndrome, particularly an unusual form of Sweet’s syndrome called Sweet’s panniculitis or Subcutaneous sweet’s syndrome.

Differences between Sweet’s syndrome and Erythema nodosum.

Where are the lesions?

  • Sweet’s syndrome: commonly appear on the face, neck and upper parts of the body, e.g. arms, but can also develop in other areas. Can affect the mucosal membranes, e.g appearing as mouth ulcers and rarely, genital ulcers. On rare occasions can form in internal joints and organs.
  • Erythema nodosum: most commonly appear on the lower legs but can occur on the thighs, trunk and forearms. Rarely appear on the face unless associated with leprosy.

What do the skin lesions look like?

  • Sweet’s syndrome: may be few or numerous. Can appear as bumps, blisters, pus-filled bumps, plaques (small lesions that join up and spread out to form large, raised red patches), ring-shaped lesions, abscess-like lesions and ulcers.
  • Erythema nodosum: may be few or numerous. Red bumps most commonly appear on the shins or about the knees and ankles. At first the bumps are bright red, later becoming purple and fading through the colour change of a bruise. Rarely, larger lesions join up to form a crescent shaped ring. The lesions never appear as ulcers.

Are the skin lesions painful?

  • Sweet’s syndrome: can be tender & painful. May cause a hot, throbbing pain.
  • Erythema nodosum: when they first appear the lesions can be hot and painful.

How long do the lesions last for?

  • Sweet’s syndrome: may last for days or weeks. Without treatment they can last for several months. In at least 1/3 of cases the lesions come back again.
  • Erythema nodosum: lesions last for approximately 2 weeks but new lesions can continue to appear for 6 weeks. Lesions can take up to 2 months to completely fade.

Other symptoms:


  • Sweet’s syndrome: almost always occurs. Less common in malignancy-associated Sweet’s syndrome. Fever – normally 38 degrees centigrade (100.4 degrees fahrenheit) or above.
  • Erythema nodosum: low-grade fever (below 38 degrees centigrade).


  • Sweet’s syndrome: no cough (a cough may be present when lesions form in the lungs, but this is rare).
  • Erythema nodosum: cough may be present.

Fatigue and general unwellness/flu-like symptoms

  • Sweet’s syndrome: yes.
  • Erythema nodosum: yes.


  • Sweet’s syndrome: conjunctivitis and other eye problems can occur (see ‘A List of Eye Problems Associated With Sweet’s Syndrome’).
  • Erythema nodosum: conjunctivitis less commonly occurs.

Joint pain and swelling

  • Sweet’s syndrome: frequently occurs. Can be widespread and affect numerous joints. Tends to disappear once the lesions are brought under control.
  • Erythema nodosum: frequently occurs. Almost always affects the knees, and less commonly other large joints. Symptoms can persist for several months (sometimes up to 2 years) after the lesions have healed.


  • Sweet’s syndrome: blood tests showing raised white cell count, raised ESR (erythrocyte sedimentation rate) and raised CRP (C-reactive protein). Punch, incisional or excisional biopsy showing lots of neutrophils (a type of white blood cell) in the tissues and no inflammation of the vessels. N.B. Inflammation of the vessels can occur in lesions more than 1 week old as a result of neutrophils releasing toxic substances (see ‘Histological Differences and Variants’ for further information).

*An incisional or excisional biopsy is needed to accurately diagnose the variant Sweet’s panniculitis or Subcutaneous sweet’s syndrome (a form of Sweet’s syndrome that affects both the skin and fatty tissue under the skin). Even a 6mm punch biopsy does not always penetrate deeply enough to obtain an adequate sample.

For information on punch, incisional and excisional biopsies see ‘What is a biopsy: do you need one?’

  • Erythema nodosum: blood tests showing raised white cell count, raised ESR and raised CRP. Erythema nodosum affects the fatty tissue under the skin so an incisional or excisional biopsy is needed for accurate diagnosis. Biopsy results should show radial granuloma – a collection of neutrophils surrounded by histiocytes (cells that remove foreign materials from blood and tissues). Only very rarely does inflammation of the blood vessels occur.


  • Sweet’s syndrome: other tests may be required to detect underlying malignancy or other conditions.
  • Erythema nodosum: other tests may be required to detect infectious causes or other underlying conditions.

Sources and further information:

A List of Eye Problems Associated With Sweet’s Syndrome http://sweetssyndrome.wordpress.com/2013/09/29/a-list-of-eye-problems-that-can-be-caused-by-sweets-syndrome/

Erythema nodosum (DermNet NZ) http://www.dermnetnz.org/vascular/erythema-nodosum.html

Histological Differences and Variants http://sweetssyndrome.wordpress.com/2013/04/22/histological-differences-and-variants/

Schwartz, R. and Nervi, S. (2007) Erythema Nodosum: A Sign of Systemic Disease. American Academy of Family Physicians (AFP Online)  http://www.laboratoriosilesia.com/upfiles/sibi/R0307227.pdf

Sweet’s Panniculitis (Subcutaneous Sweet’s Syndrome) – A Rare Variant

Sometimes, Sweet’s syndrome can occur in an unusual form. This is known as a disease variant.

Sweet’s panniculitis or Subcutaneous sweet’s syndrome is a rare form of Sweet’s syndrome where both the skin and fatty tissue under the skin can become inflamed. It is sometimes associated with cancer, particularly blood cancers (leukaemias).

Lesions in the form of coin-sized red areas and red circular bumps appear under the skin, and these may be tender. Lesions mainly appear on the extremities, e.g. shins, ankles, hands and wrists. When the inflammation has settled, a depression in the skin may be left behind temporarily or permanently. This is called localised lipodystrophy. Sweet’s panniculitis can look just like the condition Erythema nodosum.

Sweet’s panniculitis is diagnosed via incisional or excisional biopsy (even a 6 mm punch biopsy does not always provide an adequate sample as it may not penetrate deeply enough), and more than one biopsy from different parts of the body may be needed. This is because Sweet’s panniculitis can appear at the same time as Erythema nodosum, or one condition can appear after the other.

*There is also a Subcutaneous histiocytoid variant. See ‘Sweet’s Syndrome Variants’.

Further information:

Jihyun, K. et al (2010) A Case of Sweet’s Panniculitis Associated with Spinal Metastasis from Prostate Cancer (PMC Online) http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991733/

Erythema nodosum (DermNet NZ) http://www.dermnetnz.org/vascular/erythema-nodosum.html

What is a biopsy? Do you need one? http://sweetssyndrome.wordpress.com/

Histiocytoid Sweet’s Syndrome: A Histological Variant of Sweet’s Syndrome

Sometimes, Sweet’s syndrome can occur in an unusual form. This is called a disease variant. Histiocytoid sweet’s syndrome is a histological variant. This means that the biopsy results of people with Histiocytoid sweet’s syndrome will be different from the biopsy results of people with Sweet’s syndrome. Despite the differences in biopsy results, Histiocytoid sweet’s syndrome ‘behaves’ in the same way as Sweet’s syndrome.

*Less commonly, Histiocytoid sweet’s syndrome is caused by medication – Bortezomib and possibly, trimethoprim-sulfamethoxasole.

Differences in biopsy results:

In Sweet’s syndrome mature neutrophils (a type of white blood cell) gather in the tissues.

In Histiocytoid sweet’s syndrome immature cells not mature neutrophils gather in the tissues and can be mistaken for histiocytes (immune cells that eat foreign substances). Histiocytoid sweet’s syndrome can be confused with the condition leukaemia cutis.

*There is also a Subcutaneous histiocytoid variant. Please see ‘Sweet’s Syndrome Variants’.

Medical articles:

Histiocytoid Neutrophilic Dermatoses and Panniculitides: Variations on a Theme (Biblioteca) http://www.biblioteca-innsz.org.mx:8080/xmluiNutricion/bitstream/handle/123456789/10588/842.pdf?sequence=1

Histiocytoid Sweet Syndrome:  A Dermal Infiltration of Immature Neutrophilic Granulocytes (JAMA) http://archderm.jamanetwork.com/article.aspx?articleid=396993

Histiocytoid Sweet syndrome: Report of two cases and review of the literature (Dermatologica Sinica) http://www.dermatol-sinica.com/web/data/35c950.pdf

What is a Biopsy? Do You Need One?

A biopsy is a medical procedure that involves taking a small sample of tissue so that it can be examined under a microscope. In patients with suspected Sweet’s syndrome the sample will be taken from a skin lesion (an area of skin where abnormal changes have occurred).

The term biopsy is often used to refer to both the act of taking the sample and
the tissue sample itself.

Is a biopsy necessary?

YES! Sweet’s syndrome cannot be accurately diagnosed via visual examination of your lesions or blood tests alone. A biopsy is needed to detect certain changes in the tissues.

What type of biopsy will you need?

A punch biopsy is the commonest type of biopsy. A special instrument is used to punch a small hole in the skin to obtain a skin sample. Occasionally, an incisional or excisional biopsy is needed where a larger section of tissue is taken away with a scalpel. An incisional biopsy is where some of the tissue is taken away, and an excisional biopsy is where the entire lesion is taken away.

*An incisional or excisional biopsy is needed to diagnose a form of Sweet’s syndrome called Sweet’s panniculitis or Subcutaneous sweet’s syndrome. This form affects both the skin and fatty tissue under the skin. Even a 6mm punch biopsy does not always penetrate deeply enough to obtain an adequate sample.

*Excisional biopsy may be used to remove lesions that are thought to be cancerous.

How many biopsies will you need?

Sweet’s syndrome can sometimes occur at the same time as other conditions that affect the skin, so you may need biopsies from different lesions. These lesions might be on different parts of your body.

Sometimes, the changes that occur in older lesions can affect biopsy results so to get an accurate diagnosis you might need to have another biopsy of a newer lesion.

Does a biopsy hurt?

Before you have a biopsy you will be given a local anaesthetic to numb the area. After the anaesthetic has worn off you may experience soreness or a dull ache. This can be treated with painkillers on the advice of your doctor.

If you have an incisional or excisional biopsy you will need stitches and a dressing before you leave.

How soon will you get your biopsy results?

How quickly you get the results of a biopsy will depend on the urgency of your case and the hospital where you had the procedure. Sometimes your results will be available within a few days but it can take longer.

Sweet’s Syndrome in Pregnancy

In 2% cases, Sweet’s syndrome is pregnancy-associated. It has only been reported in the first and second trimesters and tends to occur in a milder form – but not always. In all known cases, no harm to the baby has occurred.  Symptoms often disappear after delivery, and this may be linked to lower levels of oestrogen and progestogen.

Treatment: normally steroid tablets or creams, but other treatments can be considered. Potassium iodide and biologic agents must NOT be used. Obstetric monitoring must be performed as for an at-risk pregnancy.

Pregnancy-associated Sweet’s syndrome may be confused with conditions such as cellulitis,  urticarial vasculitis, eosinophilic panniculitis and herpes gestationis.