Diagnosis of Atopic Eczema from Western Medical Perspective

Pathophysiology for Medical Herbalists

ABSTRACT

Diagnosis of atopic eczema can be difficult as there many forms of eczema and some characteristics are often shared. In addition, there are comorbidities, overlaps, where two conditions can co-exist, and complications from bacterial and viral secondary infections. However, it is widely accepted that the U.K developed diagnostic criteria is the most validated and reliable way of determining the condition since no is no specific diagnostic test available.

There are number or conventional and CAM treatment options available. Conventional western medicine sees the use of topical corticosteroids and calcineurin inhibitors, bleach baths and phototherapy as potential treatment routes. Whilst CAM management solutions could include both topical and internal preparations of herbs such as

Echinacea purpurea,


Urtica dioica,


Glycyrrhiza glabra

and

Stellaria media.

In addition, as atopic eczema has a strong genetic links there is some argument that prophylactic measures could be used should at-risk individuals be identified.

Either way the complexity of the condition necessitates a patient-centric strategy be employed for treatment.

INTRODUCTION

Eczema and dermatitis are terms often substituted for one another to denote an inflammatory skin disease (Mitchell and Kennedy, 2006). There are many types of eczema, but they are generally split into two categories as either endogenous (constitutional) or exogenous (contact) conditions. Atopic eczema, the most common form is classed as a constitutional condition (Kumar and Clark, 2017).

ATOPIC ECZEMA

Atopic eczema (AE) is prevalent amongst infants and children, affecting approximately 20% (Kumar and Clark, 2017). The incidence in adults is lower at between one and three percent (Lee et. al, 2016), and whilst not well understood, 80-90% of children’s symptoms disappear of their own volition, with 50% of suffers being symptom free by age 6. Symptoms can however reoccur in adulthood. If onset is in late childhood or adulthood it is more likely to present as a chronic rather than acute condition (Kumar and Clark, 2017).

Like all forms of eczema, AE presents with inflammation causing erythema. The condition creates changes to the skin’s surface creating a dry, scaly and highly pruritic rash (Kumar and Clark, 2017). In acute AE, spongiosis can occur as keratinocytes become enlarged with fluid in the epidermis (Mitchell and Kennedy, 2006). As the condition degenerates, fluid erupts causing vesicles or bullae in the skin. Pruritus often causes sufferers to scratch the affected site causing serosanguinous exudate and crusts (Kumar and Clark, 2017). In chronic AE, lichenification is common, as the skin thickens with irritation (Siegfried and Herbert, 2015).

In babies, the face, trunk and extensor surfaces are commonly affected (Siegfried and Herbert, 2015), manifesting on the cheeks, before spreading further (Kumar and Clark, 2017), but usually avoiding the bottom and groin (Siegfried and Herbert, 2015). In children AE is found in flexural surfaces of the knees, elbows, ankles and wrists, whilst in adults the typical morphology is on the hands (Siegfried and Herbert, 2015).

There are a number of comorbidities associated with AE and the development of other atopic diseases is common (Siegfried and Herbert, 2015). AE is usually the first step in what is referred to as ‘atopic march’, a sequence of other diseases such as allergic rhinitis, asthma, food and environmental allergies (Kapur et. al, 2018).

AE suffers are prone to secondary infections, due to altered skin microbiome (McPherson, 2016). Staphylococcus aureus (S. aureus), colonises in 90% of patients (Kapur et. al, 2018) regardless of whether the skin is healthy or inflamed (Siegfried and Herbert, 2015). Dry skin, scratching and trauma can then lead to bacterial infections (McPherson, 2016). Since skin culture tests can’t distinguish between colonisation and infection, diagnosis for secondary infections like Impetigo cannot be done by laboratory tests alone and must be reviewed alongside clinical signs (Siegfried and Herbert, 2015).  Erythema, oedema and crusted yellow papules are all indicators (Kumar and Clark, 2017).

Initially thought to be caused by immune dysfunction alone it is now widely accepted that the pathogenesis of AE is a complex blend of skin barrier function, genetics, immune dysregulation and exogenous factors (Kapur et.al, 2018). Children with AE are more likely to have a filaggrin gene (FLG) mutation especially in those with early onset or chronic AE and atopic march (McPherson, 2016). Filaggrin deficiency results in dry skin due to transepidermal water loss, this creates poor barrier function and antigens and microbes then enter through the epidermis (Kumar and Clark, 2017). Even without the FLG mutation reduced barrier function is common due to pruritis and inflammation, leaving allergens such as dust mites, pollens, grass and pet dander to penetrate and cause an immune response. Conversely, not all children with the FLG mutation develop AE, so it is clearly not the only factor at play (McPherson, 2016).

Despite AE having a clear set of features, diagnosis is not always straightforward. This is because there are other conditions that mimic symptoms, plus it is entirely possible to have two different skin conditions that coexist (referred to as overlap) or a secondary infection that creates complications (Siegfried and Herbert, 2015).

AE has different clinical signs at different ages, as do other skin conditions and this can thwart diagnosis. In infants and children psoriasis, although not as common, may be misdiagnosed as AE because the plaques associated with psoriasis are much less obvious and often appear on the face (Siegfried and Herbert, 2015). With psoriasis-eczema overlap, patients will present with flexural eczema and the lesions associated with psoriasis lack their thick plaque appearance. Unlike the singular form of psoriasis, they are also more prone to be pruritic (Siegfried and Herbert, 2015).

The secondary skin infections associated with AE are open to misdiagnosis. In addition to bacterial infection patients are susceptible to viral infections, such as eczema herpeticum (EH). EH, which can be fatal, is caused by the herpes simplex virus and manifests in areas of the skin affected by chronic atopic eczema (Kapur et.al, 2018). However, it can be easily misdiagnosed as a bacterial infection. Due to colonisation, a positive skin culture test could still confirm the presence of staphylococcal or streptococcal bacteria but not exclude EH. Whilst diagnosis could be determined by skin scrapes, viral cultures and immunofluorescence, these tests have poor sensitivity leading to the potential of false negatives (Siegfried and Herbert, 2015). This clearly has significant implications for treatment as each condition requires a different solution (Kapur et.al, 2018).  Overall, 10-20% of patients contract EH and they are more likely to have had recurrent S. aureus infections, with a higher incidence of other atopic conditions and severe or early onset AE (Siegfried and Herbert, 2015).

There is no specific diagnostic test for AE (Kapur et.al, 2018) and due to the varying ways it presents in patients (severity, appearance and distribution), there is difference of opinion regarding classification (Brenninkmeijer et. al, 2007). A variety of different diagnostic criteria exist but Brenninkmeijer et.al conducted a systematic review of each of these and concluded that the U.K. criteria, was the most extensively validated (2007). The U.K. diagnostic cites patients must have an itchy skin condition plus three or more of the following for adults and older children: a history of asthma or hay fever, flexural dermatitis, dry skin in the last 12 months, onset of rash under the age of 2 years. In children under four they must have the same major criteria but with a history of itching on the cheeks, atopic diseases in a first-degree relative and dermatitis to the cheeks, forehead and exterior limbs (Williams et. al, 1994).

Glucocorticoids, a type of topical corticosteroid (TCS) are often the first choice for medical treatment. TCS vary in terms of potency to allow for age, site of application and severity (Lee et. al, 2015). Corticosteroids have anti-inflammatory, antiproliferative, and immunosuppressive actions and to maximise efficacy they are applied under skin emollients. Long-term use can have side effects including striae, petechiae, telangiectasia, skin thinning, atrophy and acne (Kapur et.al, 2018).

Emerging worries regarding topical steroid withdrawal (TSW) is causing patients to stop the use of TCS. TSW is a condition that occurs when long-term TCS treatment ceases, signs include burning pain, red skin (both on the site of application and to areas of untreated skin), red sleeve – a rebound AE eruption to the limbs that ends suddenly at the dorsal and palmar boundary, headlight sign – erythema to the entire face excluding the nose with perioral dermatitis and finally, elephant skin – thickened, wrinkly skin often on the anterior knees and extensor elbows (Sheary, 2018).  A recent Australian study found that 65% of TSW sufferers had been using potent TCS on their face and 42% had been using an oral corticosteroid (Sheary, 2018). This then perhaps leads to an interesting debate regarding prescription and patient education. In that milder steroids, such as hydrocortisone, should only be used on the face leaving the more potent applications such as fluocinolone acetonide for palmoplantor skin where the stratum corneum is thicker (Kumar and Clark, 2017).

Topical calcineurin inhibitors (TCIS), such as pimecrolimus and tacrolimus, are immunosuppressants. They tend to be gentler than TCS and are not prone to skin atrophy (Kumar and Clark, 2017). They are good option for sensitive areas like the eyes, face and genitals (Kapur et.al, 2018) but are less effective on thicker lichenified skin (Kumar and Clark, 2017). Common side effects, which cease with continued use, are skin burning and irritation. There is some concern regarding their immunosuppressant ability and the risk of skin cancer (Kapur et.al, 2018). Therefore, caution is advised regarding sun exposure and vaccinations (Kumar and Clark, 2017).

Phototherapy is indicated in the treatment of adult AE, but its long-term effects remain unknown (Kapur et.al, 2018). UVB and UVA are reported to have immunosuppressive effects on the skin (Kumar and Clark, 2017). Narrowband UVB is the preferred form of treatment as it is less carcinogenic than UVA, which is also ineffective when used on its own (Kumar and Clark, 2017).

For secondary

S. aureus

infections, short-term antibiotic therapy is indicated with either cephalosporins or anti-staphylococcal penicillin (Kapur et.al, 2018). Whilst antibiotics do eradicate AE infections, there are growing problems associated with resistance (McPherson, 2016). An alternative treatment is the use of bleach baths which involves soaking in a bath at a comparable concentration to that of a chlorine swimming pool (Kapur et.al, 2018) and reports show an improvement in symptoms after a period of 3 months (Huang et. al, 2009).

For EH the systemic antiviral treatment acyclovir is a common treatment (Kapur et.al, 2018). This presents challenges as acyclovir resistance is developing and since EH reoccurs in 50% of patients, other antiviral agents will need to be found (Frisch and Seigfried, 2011).

CAM APPROACH

There a number of indicated herbs that could be considered both internally and topically.

Echinacea purpurea

radix aids the management of AE on a number of levels. Firstly, with its ability to boost the immune response, Echinacea is indicated in the presence of S. aureus infections. It is thought that it may also be able to move the immune response away from a Th2 to Th1 response. This is of particular interest as whilst both Th1 and Th2 both play a part in the production of immunoglobulins, it is only Th2 cells that stimulate IgE, the immunoglobulin associated with allergic reactions in response to environmental antigens (Hoffman, 2003). The efficacy of the epidermal barrier also relies on the immune system because Th2 cytokines have been shown to reduce filaggrin and other proteins causing further damage to the epidermal barrier thus letting in more antigens and creating a vicious circle (Darsow et. al, 2013). A recent randomized, double-blind, placebo-controlled clinical study found

Echinacea purpurea

cream alleviated symptoms of AE by demonstrating both anti-inflammatory actions and restoring the epidermal barrier (Olah et.al, 2017).

Calendula officinalis

contains antibacterial, antiseptic, anti-inflammatory and antimicrobial properties, alongside its skin healing ability it is an effective preparation for skin issues susceptible to infection (Chevallier, 2000). In the case of AE, Calendula is indicated as a topical treatment to control skin microflora imbalance and to treat S. aureus infection (Bone and Mills, 2013).

Glycyrrhiza glabra

contains glycyrrhizin which has an anti-inflammatory affect like hydrocortisone and other corticosteroids. It stimulates hormone production in the body by acting on the adrenal glands and increasing the anti-inflammatory action of cortisol,

as well as inhibiting the breakdown of steroids by the liver (Chevallier, 2000). Glycyrrhiza is indicated in supporting those patients wishing to withdraw from steroidal anti-inflammatory drugs and studies show that it inhibits IgE production and reduces scratch behaviour in mice (Bone and Mills, 2013).

Urtica dioica

, is known for its anti-allergenic actions and is a valuable agent in treating allergic rhinitis, asthma and AE, all conditions associated with atopic march (Chevallier, 2000).

Antipruritics herbs reduce the sensation of itching, alleviating uncomfortable symptoms and protecting the skin barrier by reducing trauma (Hoffman, 2003).

Stellaria media

is one herb that works in this way and can be used as a topical cream or as an infusion added to a bath (Chevallier, 2000).

McPherson suggests that altering a high-risk infant’s environment could impede the onset of AE and atopic march. Studies suggest that avoidance of soap, which increases transdermal water loss and pH causing downregulation of FLG, can reduce the risk of AE development (2016). Furthermore, administering probiotics to the mothers of at-risk children during pregnancy and breast feeding can improve microbiome (McPherson, 2016).

The role of food allergens in AE is somewhat controversial. Whilst it is clear that many patients with AE experience high IgE antibodies and that some foods may act as triggers, recent research highlights the need for care with exclusion diets that avoid allergenic food, citing that these may inadvertently exacerbate or cause food intolerances (Kapur, 2018). Instead new thinking is that the immune system of high-risk individuals should be exposed to potential allergenic foods earlier (McPherson, 2016).

CONCLUSION

AE is a common and complex disease. Secondary infections, comorbidities and overlap complicate the overall picture and differential. Recent research into the pathophysiology of AE suggests a combination of genetics, skin barrier disfunction, immune dysregulation and external factors. With this in mind a multifaceted patient-centric approach to management of the condition must be employed, in addition, there are some potential prophylactic measures, which could be adopted for high-risk individuals.

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