Eczema – Etiopathogenesis Treatment Management and Repertorial Approach

Dr Appu Gopalakrishnan

The terms ‘eczema’ and ‘dermatitis’ are synonymous. There are a number of clinical variants, which are all characterised by acute orchronic inflammation and spongiosis (oedema) of the dermis and epidermis on histology¹.

Atopic eczema
Generalised, prolonged hypersensitivity to common environmental antigens, including

pollen and house dust mites, is the hallmark of atopy, in which there is a genetic predisposition to over-production of IgE. Atopic individuals manifest one or more of a group of diseases that includes asthma, hay fever, food and other allergies, and atopic eczema. The identification of null alleles in the filaggrin gene predisposing to atopic eczema (and asthma in association with atopic eczema) has dramatically increased our understanding of the pathogenesis of atopic eczema. Filaggrin is an important component of the skin barrier and it is the combination of this defect with exposure to environmental allergens that is likely to cause the clinical signs of atopic eczema².

Pathophysiology

The clinical hallmarks of Eczema can be  explained by two main features:

Disturbance of epidermal barrier
A profoundly disturbed epidermal barrier leads to dry skin as a consequence of a high transepidermal water loss on  one hand and to enhance penetration of irritant substances and allergens into the skin on the other side. The disruption of the epidermal barrier may be caused by genetic alterations such as null mutations in the gene filaggrin that strongly predispose to development of eczema or ichthyosis. Filaggrin is expressed in the upper layers of the stratum corneum and is encoded within the epidermal differentiation complex (EDC).

Besides genetic determination, the epidermal barrier function also depends on the immune system. It has been demonstrated that  cytokines such as IL-4 inhibit the expression of filaggrin and S100 proteins and thus impair the epidermal barrier. Mechanical (scratching) or physical (hot water, UV exposure, sweating) irritation further weakens the epidermal barrier.

Deviated immune response, allergy, and impaired innate immunity
Eczema  is typically characterized by a Th2 dominated immune response both in skin and in circulation. This is especially true for atopic eczema (formerly called extrinsic atopic eczema), but also for other kinds of eczema such as non-atopic eczema (formerly called intrinsic atopic eczema), allergic contact dermatitis, and nummular or dishydrotic eczema. The Th2 prevalence is partially based on genetic predisposition (e.g. mutations in the IgE receptor ) and/or on the nature of the antigen causing an immune reaction. Increasing evidence suggests that for example pollen-derived low-molecular weight substances favor a Th2 immune response.

In lymphoid tissue, Th2 cells induce the production of IgE antibodies by plasma cells. Increased total and allergen specific IgE is a typical hallmark of atopic eczema. In contrast, type I allergic reactions with food allergen specific IgE regularly cause Eczema exacerbations in young children. The most common allergens are milk, egg, peanut, soy, and cereals. These allergies are typically lost during school age. In adults, a subpopulation of E patients may also react with exacerbation to some allergens, most commonly to aeroallergens such as house dust mite or pollen. The atopy patch test might help to identify those patients.

In the skin, Th2 cells induce an inflammatory reaction involving mast cells and eosinophil granulocytes. Importantly, Th2 cytokines such as IL-4, IL-5, and IL-13, inhibit the induction of an adequate innate immune response of epithelial cells. This is why the patients display lower amounts of antimicrobial peptides in the skin than for example psoriasis patients. The reduced innate immunity explains why the skin of almost all patients are frequently colonized with Staphylococcus aureus. There is a correlation of the number of staphylocci and the severity of eczema, most likely due to release of exotoxins such as staphylococcus enterotoxin A/B. Also other microorganisms such as the yeast Malassezia furfur (formerly called Pityrosporum ovale or orbiculare) or the Molluscum contagiosum virus are regularly detected on  skin. Primary infections with herpes simplex virus (Eczema herpeticum) are often severe in atopic eczema patients and require hospitalization.

While acute  lesions are infiltrated by a vast majority of Th2 cells, more chronic lesions are characterized by a broader immune response of mostly Th1, Th2, and Th22 cells. In line with that observation, the clinical hallmarks of acute versus chronic cases are strikingly different, but the reduced epidermal barrier function with dryness of the skin and the skin colonization with extracellular microorganisms are constantly observed throughout all stages .

Co-factors of pathology: irritants and psychoneuroimmunology
The dry skin with reduced epidermal barrier function causes a non-specific hypersensitivity of the skin towards all kinds of irritant factors. This involves substances with irritative potential (e.g. citrus fruits, rough woolen clothing, tobacco smoke) and physical factors (sweating, cold, heat, extensive washing).

There is no doubt that psychology greatly influences eczema, and most patients report stress results in aggravation of the disease. The field of psychoneuroimmunology is rapidly evolving and initial theories report a functional and morphological interaction of mast cells, neuropeptides, and nerve fibers.

It is currently under debate whether psychiatric and/o psychosomatic diseases are associated with eczema. While initial studies reported an association with attention deficit hyperactivity disorder in children, the current concept assumes concentration problems in children might occur secondary as a consequence of the permanent and agonizing itch and sleep loss.

Increased IgE production
IgE antibodies and positive Atopy Patch Test have been found in the majority of adult patients with atopic eczema. The inflammatory infiltrate in  lesions mainly consists of CD4+ T lymphocytes, and a correlation with disease activity can be shown by the proportion of activated and unactivated CD4+ cells. In the early lesions Th2 cells predominate, later in the more chronic phase Th1 cells prevail.

More than in other allergic diseases, eczema is characterized by increased serum IgE levels. T cells play a major role in regulation of IgE production. The Th2 subtype secreting the cytokines IL-4, IL-5 and IL-13 is most important.

Cell-mediated dysfunction
As patients  are prone to develop a variety of infectious diseases of fungal, viral or bacterial origin like candidiasis, eczema herpeticum (Kaposi´s varicelliform eruption), or staphylococcal impetigo, defective cellular immunity has been suspected. However, the hypothesis of a lower prevalence of T cell-mediated contact allergy  has been questioned. Greater prevalence rates of contact allergy are found in  patients . Rather, these patients show a different contact allergen spectrum compared to individuals lacking the atopic constitution (metal allergy more frequent; lanolin, fragrance, etc. less frequent).

Food allergy and other non-allergic food hypersensitivity
An exacerbation of atopic eczema by foods in food allergic patients has been repeatedly reported, with the vast majority of cases seen in children. This should be considered in the management  when there is a history of food allergy, or when conventional treatment measures are ineffective. Whereas the IgE-mediated reactions are the most common ones, a non-immunological hypersensitivity reaction to food additives can also worsen the conditio in some cases. An appropriate diagnosis of the suspected food allergy should be made.

Aeroallergens
Some patients  suffers exacerbations of their skin lesions after contact with certain aeroallergens, e.g., house dust mite, pollen or animal dander, and improve after appropriate avoidance strategies have been applied. In certain patients,  skin lesions can be induced by epicutaneous patch testing with aeroallergens, e.g. house dust mite. The term “atopy patch test” (APT) has been proposed for this test procedure.

Skin barrier
The clinical appearance of  inflamed lesions emerging on dry, scaling skin is suggestive of an impairment of skin barrier function. An enhanced transepidermal water loss (TEWL) and reduced skin surface water content are physical parameters that directly reflect this impaired barrier function. The barrier function is maintained by the stratum corneum which forms a continuous sheet of alternating squamae, which are protein-enriched corneocytes embedded in an intercellular matrix, consisting mainly of non-polar lipids which have developed as lamellar sheets. Even uninvolved skin of E patients is characterized by distinct differences in skin surface lipid composition, especially in the ceramide fraction.

Microbial colonization
Profound changes in cutaneous flora occur in some patients  and the pathogenic importance of microbial organisms is recognized. Among these, Malassezia furfur and Staphylococcus aureus seem to play a major role. S. Aureus is responsible for a known, very often quite dramatic complication , named “impetiginised eczema,”, and in addition S. aureus may act as a persistent allergen stimulating IgE antibody production, or as an irritant with inflammatory potency when colonizing atopic skin. The inflammatory reaction may be caused by enterotoxin production, possibly with superantigen effects. More than 50% of S. aureus isolates cultured from patients with E have the ability to produce these enterotoxins. It is speculated that staphyloccocal superantigens, when released within the epidermis, cause a marked immune stimulation. The ability of staphylococcal enterotoxin B to elicit dermatitis after application to intact normal or intact atopic skin has been shown.

Psychosomatic factors
Severity of pruritus  has been described as directly related to severity of depressive symptoms. Increased itch and sweating in lichenified skin areas, following emotional stimuli, can be recorded by psychophysiological methods. Investigations of parent-child relationships have shown different emotional responses from diseased children when compared to controls. Increased “fear scores” on personality questionnaires of patients with eczema have been reported by different investigators. Stressful emotional events have been shown to precede the deterioration of  symptoms. Partner conflict situations in the parents are associated with a higher risk  in the offspring. Further investigations in the field of psychoneuroimmunology may shed light on the reasons for the contradictory results³

Clinical features
Acute atopic eczema presents with severe itch, redness and swelling.Papules and vesicles may be evident, along with scaling and cracking of the skin, which is excessively dry. In patients with chronic eczema, lichenification may be found (dry, leathery thickening of the skin with increased skin markings, secondary to constant rubbing/ scratching). The distribution of atopic eczema varies with the age of the patient: in infancy and adulthood the eczema tends to affect the face and trunk, while in childhood it affects the limb flexures, wrists and the ankles⁴.

Seborrhoeic eczema
This condition, which is characterised by a red scaly rash, classically affects the scalp (dandruff), central face, nasolabial folds, eyebrows and central chest. It is thought to be a reaction to Pityrosporum yeastinfection of the skin⁵.

Discoid eczema
This is common and characteristically consists of discrete coinshaped eczematous lesions, which may become infected, most commonly on the limbs of men⁶.

Irritant eczema and allergic contact eczema
These terms refer to eczematous eruptions of the skin in response to exogenous agents. Detergents, alkalis, acids, solvents and abrasive dusts are common causes of irritant eczema. Allergic contact eczema represents a type IV hypersensitivity reaction to an exogenous agent. Nickel, parabens (a preservative in cosmetics and creams), colophony

(in sticking plasters) and balsam of Peru (in perfumes) are common causes of allergic contact eczema. Both types of eczema account for a large amount of work loss. Patch testing may be helpful in diagnosis⁷.

Asteatotic eczema
This occurs in dry skin, most often on the lower legs of the elderly, as a rippled or ‘crazy paving’ pattern of fine fissuring on an erythematous background. Low humidity caused by central heating, over-washing and diuretics are contributory factors⁸.

Gravitational (stasis) eczema
This occurs on the lower legs and is often associated with signs of venous insufficiency (oedema, red or bluish discoloration, loss of hair, induration, haemosiderin pigmentation and ulceration)⁹.

Lichen simplex
This describes a localised plaque of lichenified eczema caused by repeated rubbing or scratching. Common sites include the neck, lower legs and anogenital area¹⁰.

Pompholyx
Intensely itchy vesicles and bullae occur on the palms, palmar surface and sides of the fingers and soles. Pompholyx may have several causes, which include atopic eczema, irritant and contact allergic dermatitis and fungal infection¹¹.

Investigation and management of eczema
Patch tests are performed if contact allergic dermatitis is suspected.Bacterial and viral swabs should be taken where supra-infection issuspected. Herpes simplex virus (HSV) may cause a widespread infection, eczema herpeticum; small, punched-out lesions within worsening eczema suggest secondary HSV infection. Skin scrapingsto rule out secondary fungal infection should be considered¹².

REPERTORIAL APPROACH WITH HIGHER GRADED MEDICINES FOR ECZEMA IN VARIOUS REOERTORIES

KENT

SKIN – ERUPTIONS – eczema

ARS. ARS-I.. BAR-M.. CALC. CALC-S.. CIC.. CROT-T.. DULC.. GRAPH, HEP, JUG-C,JUG-R, LAPPA,. MEZ,  OLND,PETR,. PSOR,RHUS-T, SULPH, SUL-I.

eczema – alternating with internal affections – Graph.

SKIN – ERUPTIONS – elevated  –Bry. .

SKIN – ERUPTIONS – excoriated – MERC, NAT-M, PETR, SULPH

SKIN – ERUPTIONS – fetid –PSOR., SULPH.

SKIN – ERUPTIONS – flat -BELL,. LACH

SKIN – ERUPTIONS – granular – Agar, Carb-v

SKIN – ERUPTIONS – grape shaped -CALC

SKIN – ERUPTIONS – hairy parts,on -RHUS-T

SKIN – ERUPTIONS – hard – Ant-c.. Ran-b¹³

MURPHY

Diseases – ECZEMA

ARS,  ARS-I,  BAR-M, CALC, CALC-S, CIC, CROT-T,. DULC,, GRAPH, HEP, JUG-C, JUG-R, LAPPA, MEZ, OLND, PETR, PSOR, RHUS-T,SUL-I, SULPH¹⁴

BOGERS SYNOPTIC KEY

SKIN – Eruptions; tendency to – eczema  – Bov., Dulc. Graph¹⁵. .

PHATAK S.R, CONCISE REPERTORY

Eczema – BOV,DULC, GRAPH

Eczema – beard, of – ars-i.

Eczema – digestive affections, with – lyc.

Eczema – dry children; in – calc-s.,dulc., frax., tarent., viol-t.

Eczema – hair, margins, at – hydr.

Eczema – itching without – cic.

Eczema – liver affections, with – lyc.

Eczema – menstrual affections, with – mang.

Eczema – recurrent – com.

Eczema – urine affections, with – lyc.

Eczema – washing agg – ars-i.

Eczema – sun, exposure, from – mur-ac¹⁶.

BOERICKE’S REPERTORY

SKIN – Eczema
Aethi-m. , Anac,. Ant-c., Ars. , Berb., Bov,. Calc., Canth., Carb-ac. . Cic. Clem.  Crot-t.. Graph. Hep.. . Kali-ar. Mang-act. Merc. Merc-c.. Mez.. Olnd. Petr. . Plb. . Psor. Rhus-t.. Sep. . Sul-i. Sulph.. Vinc. Viol-t..

Eczema – Acute form : Chinin-s. Crot-t.. Rhus-t.

Eczema – Behind ears : Chrysar. Graph. Hep.. Mez. Olnd. Petr.. Scroph-n.

Eczema – Of – face : Carb-ac.. Crot-t.. Sul-i. Sulph. Vinc.

Eczema – Of – flexures of joints : Aeth.. Graph.. Nat-m. . Sep. .

Eczema – Of – hands : Berb. Bov.  Graph. Hep.. Pix

Eczema – Of – neurasthenic persons : Anac.  Stry-ar.

Eczema – Of – pudendum : Crot-t.

Eczema – Of – rheumatico-gouty persons : .Rhus-t.

Eczema – Of – scalp : Calc.. Olnd.. Sel.. Vinc..

Eczema – With – pigmentation in circumscribed areas following – berb.

Eczema – With – urinary, gastric, hepatic disorders – lyc.

Eczema – Worse – after vaccination – mez.

Eczema – Worse – at menstrual period, menopause – mang-act.

Eczema – Worse – at sea shore, ocean voyage, excess of salt – nat-m¹⁶.

VON ZANDVOORT, COMPLETE REPERTORY

SKIN – ERUPTIONS – eczema

ARS, ARS-I, ARS-S-F, AUR-S, BAR-M, CALC, CALC-S, CIC, CROT-T.., DULC., GRAPH., HEP., JUG-C., JUG-R.. LAPPA,. MEZ. . OLND.. PETR. PSOR. . RHUS-T.. SUL-I. . SULPH.

eczema – alternating with internal complaints –  GRAPH.

eczema – amenorrhea, with – mang-act.

eczema – bathing in sea, from – MANG.

eczema – climacteric period, in – MANG-ACT.

eczema – neurasthenic persons, in – ANAC.

eczema – rheumatic, gouty persons, in – RHUS-T.

eczema – salt or salty food, after – NAT-M.

SKIN – ERUPTIONS – eczema – strumose persons, in – ARS-I.. CALC-I.. HEP.

eczema – sun, from – MUR-AC.

eczema – vaccination, after – AMMC.

eczema – chronic – NAT-C. PSOR.. SULPH.

eczema – dry – ALUMIN-SIL.

eczema – dry – ovulation, during – foll.

eczema – moist

BAR-C. . BOV.. CARB-V.. CLEM.. GRAPH.. HEP. KALI-BR.. LYC.. NAT-S.. OLND. PETR.. PSOR. RHUS-T. RUTA. SEL. SEP. SIL.. STAPH.. SULPH.

eczema – sore, as if excoriated – SKOOK.

eczema – syphilitic – ARS. GRAPH.. SARS¹⁷.

REFERENCE

1. Davidson,Stanley.Davidsons Principles and practice of medicine.21st ed.London Elsvier:Churchill Livingston;2010, 708
2. Prof. Dr. Ulf Darsow,Prof. Dr. Kilian Eyerich, Prof. Dr. Dr. Johannes Ring Dept. of Dermatology and Allergy Biederstein, university Munich, Germany, Eczema pathophysiology(internet), 2007(cited 2018 April 2) available from, http://www.worldallergy.org/education-and-programs/education/allergic-disease-resource-center/professionals/eczema-pathophysiology
3. Kent J.T., Repertory of the Homoeopathic. Materia Medica
4. Robin Murphy, Homoeopathic medical repertory
5. C.M Boger, A synoptic key of Materia medica
6. S.R Phatak, A Concise repertory of Homoeopathic material medica
7. O.E Boerick, Clinical repertory
8. Roger Von Zandvoort, Complete repertory.