Discover Wells Syndrome (Eosinophilic Cellulitis) - its symptoms, causes, and treatment options. Get informed at Meri Sehat for better health.

Wells Syndrome (Eosinophilic Cellulitis)

Overview

Wells syndrome, or eosinophilic cellulitis, is a rare skin disorder characterized by the sudden onset of large, swollen, fluid-filled patches that are sometimes covered with vesicles. 
&nbsp;

Dr. George Wells first described this syndrome in 1971. He reported it as a recurrent granulomatous dermatitis with eosinophilia. Later, in 1979, the name was changed to eosinophilic cellulitis. 

Wells syndrome is a rare disorder with only about 80 cases reported worldwide<a href="#accordion">[3]</a>. The disease most commonly occurs in adults but has also been reported in children<a href="#accordion">[1]</a>.

While the exact pathogenesis of the rare dermatosis is unclear, researchers predict that an inappropriate eosinophilic reaction might be to blame. Several factors may trigger the reaction, for example, certain drugs, infections, insect bites, and allergic contact dermatitis. Moreover, the disease has also been associated with diseases, such as <a href="https://merisehat.pk/disease/ulcerative-colitis">ulcerative colitis</a>, <a href="https://merisehat.pk/disease/chronic-lymphocytic-leukemia">chronic lymphocytic leukemia</a>, malignant tumors, and Churg-Strauss syndrome. However, a majority of cases are idiopathic. 
&nbsp;

Although eosinophilic cellulitis has no types, the lesions can appear in different forms<a href="#accordion">[5]</a>. These include:

<ul>
	<li>Plaque type</li>
	<li>Annular granuloma-like</li>
	<li>Papulovesicular</li>
	<li>Papulonodular</li>
	<li>Urticaria-like</li>
	<li>Bullous</li>
	<li>Fixed drug-eruption like 
	&nbsp;</li>
</ul>

In children, eosinophilic cellulitis most frequently presents as the classic plaque type. Whereas, in adults, the annular granuloma-like variant is more common. 
&nbsp;

Signs and Symptoms

Wells syndrome resembles bacterial cellulitis due to the presence of erythematous skin lesions. 

The rare disorder has a sudden onset with an itching or burning sensation before the eruption of lesions. This is followed by redness and edema. In the classic plaque type, large, painful, red, and edematous patches form and are often covered with bullae or vesicles. The appearance of several blisters or nodules is often the first sign of eosinophilic cellulitis. 

Lesions are most commonly located on the face and trunk. They may be solitary or multiple. Other symptoms include:

<ul>
	<li>Ring-shaped patches</li>
	<li>Hives</li>
	<li>Systemic symptoms (e.g., <a href="https://merisehat.pk/disease/asthma">asthma</a>, fever, and joint pain) 
	&nbsp;</li>
</ul>

As time passes, the lesions may change color to brown-red, then blue-gray and finally greenish-gray. They typically last for a few weeks to months but often resolve spontaneously. However, recurrence, with variable locations, is common. Moreover, scarring alopecia and reticular pigmentation can occur as part of long-term sequelae.&nbsp; 
&nbsp;

Causes

The exact etiology and pathogenesis of Wells Syndrome remain unclear. However, researchers hypothesize that it is an autoimmune disorder. In such a condition, your immune system mistakes the body tissue as a foreign antigen and starts to attack it, leading to its destruction. Even though most of the cases are random, some may be familial<a href="#accordion">[2]</a>. 
&nbsp;

The following are considered common triggers of Wells syndrome:

<ol>
	<li>Arthropod bites, including bites from a mosquito</li>
	<li>Viral infections (e.g., parvovirus B19, <a href="https://merisehat.pk/disease/genital-herpes">herpes </a>simplex virus, <a href="https://merisehat.pk/disease/mumps-76">mumps </a>virus, varicella-zoster virus)</li>
	<li>Dermatitis (inflammation of the skin)</li>
	<li>Leukemia </li>
	<li>Fungal infections</li>
	<li>Parasitic infections (e.g., ascariasis, toxocariasis, giardiasis)</li>
	<li>Reactions to certain drugs or metallic objects</li>
	<li>Vaccines, such as the HPV vaccine, <a href="https://merisehat.pk/disease/influenza-116">influenza </a>vaccine, tetanus vaccine, <a href="https://merisehat.pk/disease/hepatitis-b-113">hepatitis B</a> vaccine, and tetanus-diphtheria vaccine. 
	&nbsp;</li>
</ol>

Currently, there are no screening tests available for Wells disease. 
&nbsp;

Diagnosis

Due to the appearance of the lesions, eosinophilic cellulitis is often misdiagnosed as bacterial cellulitis and, thus, inappropriately treated. Therefore, if based on the clinical presentation, Wells syndrome is suspected, then a skin biopsy is the preferred diagnostic method. 

The histopathological findings reveal a higher number of eosinophils in the skin and under the tissue compared to normal, along with inflammatory patterns that are consistent with the said syndrome. This sign is usually enough as it rules out other possible causes of inflammation, such as an allergy, parasites, dermatitis, insect bites, or Churg-Strauss syndrome. 

Moreover, a complete blood count (CBC) may also be conducted. Peripheral blood eosinophilia is a common finding in 50% of cases during the acute phase<a href="#accordion">[1]</a>. However, it is not a basis for diagnosis.

As per the proposed diagnostic criteria for eosinophilic cellulitis, at least two major and one minor criteria must be present<a href="#accordion">[5]</a>. 
&nbsp;

<h5>Major Criteria</h5>

<ul>
	<li>Clinical picture demonstrating any type of lesions</li>
	<li>No evidence of any systemic disease&nbsp; </li>
	<li>On and off course of symptoms</li>
	<li>Eosinophilic infiltrates without vasculitis present on histology 
	&nbsp;</li>
</ul>

<h5>Minor Criteria</h5>

<ul>
	<li>Eosinophilia on your peripheries which is not consistent and not more than &gt;1.5 x 109/L</li>
	<li>Histology exhibiting a granulomatous change</li>
	<li>Flame figures</li>
	<li>A triggering factor (eg, a drug, insect bite, etc). 
	&nbsp;</li>
</ul>

Treatment

Other than treating the underlying cause, doctors administer steroids and dapsone for the treatment of Wells syndrome. 

&nbsp;

<ul>
	<li>Corticosteroids: Systemic corticosteroids, such as prednisone, are the mainstay treatment. It can either be injected or administered orally. The drug has an immunosuppressant effect and prevents the immune system from attacking its own cells. Corticotherapy can also help reduce the duration of illness and the risk of relapses. The initial dose ranges from 0.5 to 1 mg/kg/day but needs to be tapered off rapidly. However, tapering off can often lead to relapses. Moreover, corticosteroid dependence is also a possible side effect of the treatment.</li>
	<li>Dapsone: The aim of dapsone is to reduce the duration of relapses. A recommended treatment duration for dapsone is not available, however, it can be used for a few months in an uncomplicated disease that may require discontinuation of treatment. It can either be used alone or in a combination with other treatment options including corticosteroids. Moreover, in cases of corticosteroid dependence, dapsone can be used.</li>
	<li>Antihistamines: Hydroxyzine is often used in cases of pruritus. Due to their excellent tolerance, healthcare practitioners often use antihistamines to avoid prescribing steroid treatment. The dosages vary from 50 to 100 mg/day.</li>
	<li>Other Treatments: Some non-traditional treatment modalities for Wells Disease include the use of Colchicine, PUVA (psoralen and ultraviolet A) therapy, interferon-alpha, cyclins, synthetic antimalarials, ciclosporin, and anti-TNF agents. 
	&nbsp;</li>
</ul>

Complications, such as a superinfection are a rare occurrence. However, severe limb swelling may lead to compartment syndrome. 
&nbsp;

While the exact cause of Wells syndrome remains unclear, the following factors may trigger the disease: 
&nbsp;

<ul>
	<li>Arthropod bites, including bites from a mosquito.</li>
	<li>Viral infections</li>
	<li>Dermatitis</li>
	<li>Giardiasis </li>
	<li>Leukemia</li>
	<li>Fungal infections</li>
	<li>Certain drugs or metallic objects 
	&nbsp;</li>
</ul>

Since the cause of Wells&rsquo; syndrome is still unknown to the doctors, it has not been possible just yet to determine the ways by which one can avoid it. 
&nbsp;

Key Points

<ul>
	<li>Wells syndrome is essentially the characterization of the sudden onset of large, swollen, fluid-filled patches that are sometimes covered with vesicles.</li>
	<li>On the basis of the reported cases, the triggering factors suggested are insect bites, drugs, allergic contact dermatitis, certain malignancies, and infections.</li>
	<li>Wells syndrome is very rare and globally only 80 cases have been reported. It primarily affects adults, but can also take place in children.</li>
	<li>Symptoms characteristically start with an itching or burning feeling in either one or more areas of your skin, followed by redness and swelling. Other than this, symptoms may include ring-shaped patches.</li>
	<li>Over time, the lesions may change color to brown-red, then blue-gray, and finally greenish-gray</li>
	<li>To accurately diagnose Wells syndrome, a skin biopsy is the preferred evaluation modality.</li>
	<li>Corticosteroids and dapsone are the two primary treatment modalities for Wells syndrome</li>
	<li>Some non-traditional treatment modalities for Wells syndrome include the use of Colchicine, PUVA (psoralen and ultraviolet A) therapy, interferon-alpha, cyclins, synthetic antimalarials, ciclosporin, and anti-TNF agents</li>
	<li>If left untreated, severe swelling of a limb may take place, also known as compartment syndrome. 
	&nbsp;</li>
</ul>

[1] Toumi A, Yarrarapu SNS, Litaiem N. Wells Syndrome. [Updated 2022 Sep 26]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

[2] Wells' syndrome. Cleveland Clinic.

[3] Robert A Schwartz MD. Wells syndrome. Background, Pathophysiology, Etiology.

[4] Bansal, M., Rai, T., & Pandey, S. S. (2012). Wells syndrome. Indian dermatology online journal, 3(3), 187–189.

[5] Eosinophilic cellulitis. January 21, 2023.

[6] Cellulitis - symptoms, causes, treatments, & more. WebMD.

[7] Sinno H, Lacroix JP, Lee J, et al. Diagnosis and management of eosinophilic cellulitis (Wells' syndrome): A case series and literature review. Can J Plast Surg. 2012;20(2):91-97. doi:10.1177/229255031202000204.