What Is Familial Eosinophilic Cellulitis?

Eosinophilic cellulitis (Wells syndrome) is a rare condition with a scary name.¹ In this article, we will explain all the information you need in an understandable and sensitive way.

Introduction

Also known as Wells syndrome, eosinophilic cellulitis is an extremely rare inflammation of the skin, which can affect any age, usually appearing as a rash before itching or burning.^1,2,3 

Typically, a rapid onset of symptoms can last from 4-8 weeks, with the rash possibly reappearing multiple times in the upcoming years. However, the lesions formed by this condition tend to go away on their own.^3,4

The cause of this condition is unknown, although it is assumed that eosinophilic cellulitis is an over-reaction by the immune system, caused by an unusually high build-up of immune cells known as eosinophils, accumulated in the red and swollen areas of the skin.^3,5

This article will explore the signs and symptoms of Familial Eosinophilic Cellulitis (FEC), and also explain some details about the diagnosis briefly.

Causes and triggers

Note of discretion from the author: Although these are pieces of circumstantial evidence suggesting that these are causes and triggers of the condition, the rates of familial eosinophilic cellulitis are very low. 

According to a Canadian literature review from 2012, there have been less than 200 cases reported in the scientific literature, and the rates of some of these triggers causing the condition can be as low as one case on record, being thiomersal in vaccinations. There has only been one case of a person encountering eosinophilic cellulitis, seemingly when they were exposed to thimerosal in vaccinations.²

There have been other cases like the aforementioned, where a single person encountered the condition, seemingly when exposed to a certain trigger.⁶

Currently, the exact cause of familial eosinophilic cellulitis, or ‘idiopathic’, which entails the same meaning, is unknown.³ However, a strong presumption is that the condition could be caused by an over-reaction of the immune system.⁴ 

Better documented triggers

Triggers that are better documented of familial eosinophilic cellulitis include:³

• Infection
• Arthropod bite
• Haematological (blood system-related) disorders and malignancies

Medications and Immunisation 

Twenty-five cases of drug-induced eosinophilic cellulitis have been reported (which, given the number of individuals diagnosed with the condition, is a substantial proportion),¹ The following medications have been noted as linked to the condition:⁶

• Antibiotics 
• Anticholinergics
• Anaesthetics
• Chemotherapy agents
• Non-steroidal anti-inflammatory agents (NSAIDs)
• Thiazide diuretics
• Thyroid medication
• Thiomersal in vaccinations

Symptoms and presentation

How symptoms act

The symptoms usually share the following characteristics:^4,5

• Symptoms present rapidly
• Symptoms can reappear suddenly and intermittently, potentially persisting for years
• Symptoms could last four to eight weeks

Different symptoms

Most common symptoms

• Pruritus: Itching or desire to scratch⁷
• Cellulitis: Bacterial infection in the skin, with inflammation that can also affect tissue under the skin.⁷

Other symptoms

• Flame-shaped pattern on skin that is swollen, raised, and red; it is also warm to the touch; this can affect a large area of skin.⁵
• Fever³
• Arthralgias (multiple pains in joints, with the joints lacking swelling³
• Vasculitis (blood vessels experiencing inflammation)⁷
• Increased number of cells involved in the immune system called ‘eosinophils’ in the blood⁷
• Lesions can take many different shapes including:³
  • Annulare granuloma-like: a ring-shaped grouping of lesions with aggregated histocytes, histocytes being types of cells involved with the immune system.⁸
  • Urticaria-like (also known as hives)
  • Papulovesicular (there are both papules or small bumps and vesicles or small blisters in a rash or lesion)
  • Bullous (large, fluid-filled blisters)^3,7
  • Papulonodula: similar to papules in that they are small, raised lesions, but they have a deeper skin-related component
  • Fixed drug eruption-like: when there is a sudden emergence of multiple skin lesions (skin eruption) due to re-exposure to a specific drug or chemical. The eruption reappears at identical sites.^3,9
  • Skin vesicles (small, elevated lesions that contain fluid and are limited to an area)⁷

Diagnosis

The diagnosis of FEC is commonly controversial.⁶ Often, the condition is misdiagnosed as infectious cellulitis due to the conditions having a similar presentation.²

The “gold standard” for diagnosis of FEC/Wells syndrome includes three conditions:²

• Flame figures: A pattern on the skin that resembles a flame; the skin is red, swollen, raised, and warm to the touch.⁵
• Oedema in the dermis: A build-up of fluid in the dermis layer of your skin; this layer works to protect and support the other layers of your skin¹¹
• Infiltration of the dermis by eosinophils: immune cells known as eosinophils enter the dermis layer of the skin.²

Proposed diagnostic criteria

There is a proposed criterion for diagnosing eosinophilic cellulitis/Wells’ syndrome which at minimum requires two of the major criteria along with one of the minor criteria to be met.³ 

Major criteria (2 required)

• Histology including eosinophils gathering in the dermis without the blood vessels being inflamed²
• Being without evidence of a systemic disease
• The condition reoccurs
• Clinical interpretation points to any of the reported variants of eosinophilic cellulitis

Minor criteria (1 required)

• The number/concentration of eosinophils that gather in the blood of surrounding areas to the rash are no more than >1.5 x 10⁹/L
• Histology shows a change because of granulomas (a kind of chronic inflammation where histocytes aggregate)⁸
• Flame figures
• Something to trigger the condition

Usually, biopsies are needed to diagnose familial eosinophilic cellulitis. Moreover, the findings of a histology test are dependent on the disease stage.³

Differential diagnoses

The previously mentioned ‘flame figures’ are not only seen in familial eosinophilic cellulitis, but can be signs of other types of disease where high numbers of eosinophils build-up in parts of the body.³ 

These other diseases include:

• Bullous pemphigoid (rare; an itchy rash that develops into large blisters)¹³
• Arthropod bite reactions (arthropods include spiders, insects, mites, crabs etc.)¹²
• Eosinophilic granulomatosis with polyangiitis (a rare type of inflammation that affects small vessels (like blood vessels)¹³
• Parasitic infection³

Other common differential diagnoses

• Bacterial cellulitis and erysipelas: they are both bacterial infections that cause redness, swelling, and pain at the site of infection_,¹⁴ with cellulitis affecting the deeper portion of tissues, and bacterial erysipelas affecting the upper layers of skin tissue¹⁵

FAQs

What does familial eosinophilic cellulitis mean?

Occurring in a family regularly (familial), and to do with increased numbers of eosinophils (eosinophilic), presenting there is redness, swelling, and pain in the affected area (cellulitis), giving the name familial eosinophilic cellulitis.

In eosinophilic cellulitis, the cellulitis symptom is thought to be caused by an over-reaction of the immune system.³

Eosinophilic in this context means that something has to do with eosinophilia, which is when the number of eosinophils circulating in the blood has become higher than usual.¹⁷

Eosinophils are a type of white blood cell used by the body to protect against infection.¹⁸

Cellulitis is a redness, swelling, and pain in an affected area of skin usually caused by a bacterial infection.¹⁴ 

Where can I expect to see skin lesions from eosinophilic cellulitis?

Typically the lesions form on the limbs and extremities, but lesions have also been reported on the trunk, face, and scalp¹⁹

Does familial eosinophilic cellulitis cause scarring?

The plaques caused by eosinophilic cellulitis heal without scarring¹⁶

Is familial eosinophilic cellulitis contagious?

Studies on the condition do not appear to suggest that the condition is contagious. However, the exact cause is still unknown, with it being thought that the condition is linked to some triggering events or associated with an underlying condition¹⁹

Can familial eosinophilic cellulitis be inherited?

There have been reports of the condition likely being inherited by members of the same family^{20, 21}

Summary

Familial eosinophilic cellulitis, also known as Wells syndrome, is a rare skin inflammation triggered by an overactive immune response, often involving an abnormal accumulation of eosinophils. Symptoms include a rash, itching, and burning, lasting 4-8 weeks, with potential recurrence. Triggers range from infections to medications. Diagnosis relies on criteria like flame figures, dermal oedema, and eosinophil infiltration. Lesions appear on limbs but may affect other areas. The condition, not conclusively linked to heredity, usually resolves without scarring. Though not deemed contagious, its precise origin remains unknown. This familial variant has limited documented cases, emphasising its rarity.