ATOPIC DERMATITIS (ECZEMA) AND COMORBIDITIES

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Atopic dermatitis (AD), also known as atopic eczema, is a chronic inflammatory disorder that causes significant morbidity and has a wide range of allergic and non-allergic comorbid disorders.

Comorbidity is a concurrence of multiple diseases or disorders in association with a given disease. The patient with AD has an increased risk of developing one or more of a number of other diseases/conditions that share many immunological features with AD.

 CHART 1: Comorbidities Associated with AD

Cutaneous (skin) infections including:-

Bacterial – Staphylococcal   / Impetigo contagiosum

Viral – eczema herpeticum

Fungal

 

Other Skin Conditions:

Vitiligo

Psychological and Psychiatric Disorders – Depression

Anxiety

Attention Deficit/Hyperactivity Disorder (ADHD)

Autistic spectrum disorder (ASD)

Food Allergies/Intolerances Cardiovascular Disease – Arterial hypertension/ Atherosclerosis

Stroke

Prediabetes

Diabetes

Obesity

Fatty Liver

Dyslipidemia (Raised cholesterol)

Allergic conjunctivitis

Cataracts 

Atopic keratoconjunctivitis (AKC) 

Allergic rhinitis

Hayfever

Asthma

Acute upper respiratory infection

Acute pharyngitis

Fatigue, insomnia  

1, 2, 3, 4, 5, 6, 7

Most cases of AD begin in childhood or adolescence, with more than 80% of pediatric patients having persistent symptoms of itch and dry skin in adulthood. The early age of onset and disease chronicity, plus impaired quality of life, secondary to AD weigh heavily on a child’s psychological and behavioural development, with delayed social development throughout life and very high rates of psychological and behavioural disorders and quality-of-life impairment.6 Various studies have consistently indicated an association between AD and ADHD which is independent of environmental exposures and other comorbidities. Particularly infant AD appears to be associated with later development of ADHD symptoms. Sleeping problems due to AD are suggested as playing an important role for the observed association between AD and ADHD. Children with previous or prevalent AD have an approximately 43 % increased risk to be diagnosed with ADHD or to display clinical ADHD symptoms.8

Researchers have found that adults with AD have higher rates of cigarette smoking, consumption of alcoholic, lower rates of exercise, and higher classification of obesity with category II / III consistently indicated in children and adults, hypertension, prediabetes, diabetes, and high cholesterol.6, 7

staph-infection

Bacterial superinfection by staphylococcal aureus is the most common complication in atopic dermatitis and is almost always present in AD flares.  S. aureus is an important human pathogen that causes a variety of  infections ranging from localised skin and soft-tissue infections (SSTIs) to severe necrotising fasciitis and life-threatening infections.7 , 8  S. aureus can be isolatedfrom 55–75% of unaffected AE skin, 85–91% of chronic lichenified lesions and 80–100% of acute exudative skin lesions.9 The correlation between AD severity and colonization with S. aureus has already been well documented, and it is generally known that this colonization is an important mechanism involved in the continued aggravation of the disease in patients.

S. aureus has shown a capacity to develop resistance to antimicrobials that were originally active against the species. In 1961, there were reports of strains that were methicillin resistant, and they were called methicillin-resistant Staphylococcus aureus (MRSA). By 1980, MRSA strains became an endemic problem in hospitals in several countries. Reports on MRSA infections in AD patients have been published since 2005. Some authors suggest that MRSA should be considered when patients with AD present with more intense and generalized erythemas (redness of the skin), and with the predominant location of infection in these patients being the face, and a fetid (fishy) odour present. Studies worldwide suggest that the prevalence of MRSA in the population with AD varies from 0 to 30.8% depending upon the country of research.10

Colonization by streptococcus generally precedes the development of impetignized lesions (by about 10 days). Group A streptococci often colonize the pharynx of asymptomatic people, especially school-age children. In cases of infected atopic dermatitis lesions, a high prevalence of co-infection by staphylococci and streptococci was reported, and these bacteria were present in about 70 to 85% of patients. B-hemolytic streptococci are the main cause of impetigo and are more commonly isolated on the skin of people with AD than on the skin of healthy individuals or of those with other skin diseases.11

Eczema herpeticum (EH) is caused by Herpes simplex virus-1 (HSV-1), Herpes simplex virus-2 (HSV-2), Herpes zoster virus, Coxsackie virus, etc. Also, EH may occur in children who have AD after smallpox vaccination. If corticosteroid therapy is used in these patients because of misdiagnosis, the lesions may worsen. Therefore, if skin lesions or another pre-existing dermatitis is aggravated after varicella (smallpox) infection then EH must be considered and antiviral therapy must be started immediately.11

AD, is an immunoglobulin E (IgE)-mediated disease with a complex etiology (cause) that is accompanied by superficial inflammation and itchy rashes. An association with asthma and Allergic rhinitis (Hayfever) is well documented. Fifty percent of all those with AD develop other allergic symptoms within their first year of life. In the International Study of Asthma and Allergies in Childhood (ISAAC), among the 56 countries, the prevalence of AD in children varied significantly from 0.3% to 20.5% but shows consistent trends in increasing disease prevalence over time. The main risk factors for progression and persistence of asthma are early onset, IgE sensitization, and severity of AD. Approximate 70% of patients with severe AD develop asthma compared with 20-30% of patients with mild AD and approximately 8% in the general population. Epidemiologic studies have consistently demonstrated strong associations between rhinitis and asthma. Recent clinical and basic science evidence indicated that the two diseases share anatomical, physiological, immuno-pathological, and therapeutical factors. Allergic rhinitis is an inflammatory condition affecting nasal mucosal membranes. In sensitized individuals, allergens such as pollens, moulds, and animal dander provoke this allergic response.12, 13

The relationship between food allergy and AD is complex and the presence of food sensitization and allergy earlier in life predicts a prognosis of severe AD. Around 50–70% of children with an early onset of AD are sensitized to one or more allergens. These are mainly food allergens (cow’s milk, hen’s egg and peanuts being the foods most frequently involved). Food allergy is actually much more common in children with AD with studies reporting ranges from 20 to 80% of children being affected.12,13

Allergic conjunctivitis (AC), either seasonal and/or perennial, is one of the most common types of ocular inflammation which causes redness and swelling of the eyes. Estimates vary, but these types of allergy are said to affect at least 15–20% of the population and higher incidences in those with AD. Its pathophysiology also involves a type I IgE-mediated immune reaction triggered by allergens contacting surface of the eye.2 Atopic keratoconjunctivitis (AKC) is a bilateral chronic inflammatory disease of the ocular surface and eyelid. Its pathomechanism involves both a chronic degranulation of the mast cell mediated by IgE, and immune mechanisms mediated by Th1- and Th2-lymphocyte derived cytokines. It is considered the ocular counterpart of AD. Eczematous lesions may be found on the eyelids, or any place on the body. Skin lesions are red and elevated. They often occur in the antecubital (inner elbow) or popliteal (behind the knees) regions. Typically, eczematous lesions are itchy, and scratching them makes them itchier. Ocular findings vary. The eyelid skin may be chemotic (inflamed eyelid) with a fine sandpaper-like texture. There may be mild, or severe, red and swollen eyes.14

If you have any questions please do not hesitate to contact our clinic by either emailing us at info@goodskincare.com.au or message us on our Facebook page https://www.facebook.com/PsoriasisEczemaClinic/

 

 REFERENCES

  • Simpson EL.; Comorbidity in Atopic Dermatitis; Curr Dermatol Rep. 2012 March 1; 1(1): 29–38. doi:10.1007/s13671-011-0003-5
  • Augustin M. et al.; Epidemiology and Comorbidity in Children with Psoriasis and Atopic Eczema; Dermatology 2015;231:35–40 DOI: 10.1159/000381913
  • Deckert S. et al.; Nonallergic comorbidities of atopic eczema: an overview of systematic reviews; Allergy 69 (2014) 37–45 © 2013
  • Ellis CN. et al.; Validation of Expert Opinion in Identifying Comorbidities Associated with Atopic Dermatitis/Eczema; Pharmacoeconomics 2003; 21 (12)
  • Gradman J. et al.; Allergic conjunctivitis in children with asthma, rhinitis and eczema in a secondary outpatient clinic.
  • Silverberg J.I.; Eczema and cardiovascular risk factors in 2 US adult population studies; J Allergy Clin Immunol 2015;135:721-8.
  • Silverberg J.I. and Silverberg N.B.; Atopic Dermatitis: Update on Pathogenesis and Comorbidities
  • Baviera G. et al.; Staphylococcus Aureus And Atopic Dermatitis: Which Came First, The Chicken Or The Egg?; EMJ Dermatol. 2015;3[1]:92-97.
  • Leung DYM.; The role of Staphylococcus aureus in atopic eczema; Acta Derm Venereol 2008; Suppl 216: 21–27
  • Petry V. et al.; Bacterial skin colonization and infections in patients with atopic dermatitis; An Bras Dermatol. 2012;87(5):729-34.
  • Celtik C. et al.; A Life-Threatening Condition In A Child With Chicken Pox: Eczema Herpeticum; Open Journal of Pediatrics 1 (2011) 1-3
  • Tao Zheng et al.; The Atopic March: Progression from Atopic Dermatitis to Allergic Rhinitis and Asthma; Allergy Asthma Immunol Res. 2011 April;3(2):67-73. doi: 10.4168/aair.2011.3.2.67
  • Nutten S.; Atopic Dermatitis: Global Epidemiology and Risk Factors; Ann Nutr Metab 2015;66(suppl 1):8–16
  • La Rosa M. et al.; Allergic conjunctivitis: a comprehensive review of the literature; Italian Journal of Pediatrics 2013, 39:18 http://www.ijponline.net/content/39/1/18

PSORIASIS – the Relationship with Viral, Bacterial and Fungal Infections?

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Several viral infections have been associated with the provocation or exacerbation of psoriasis such as strep infections. Psoriasis preceded by herpes simplex virus (HSV) infection has also been reported in the past whilst other less well documented cases of viral induced psoriasis have been reported with Hepatitis B and C. Recently a case of human papilloma virus (HPV) and late onset of psoriasis has been reported. Chikungunya infection, HIV/AIDS, persistent Cytomegalovirus (CMV) infection and varicella zoster virus (VZV) have all been reported as causal and/or aggravating factors. 1,2,3,4,5,6  

The relationship between bacterial infection and the exacerbation of psoriasis is perhaps most clearly demonstrated in guttate psoriasis where there are multiple reports demonstrating that acute exacerbation of guttate psoriasis, in the majority of patients, is preceded by an infection with group A streptococci. Streptococcus pyogenes infection has also been implicated.

Guttate psoriasis is a distinctive acute form of psoriasis that generally occurs in children and young adults. The association between guttate psoriasis and Streptococcus pyogenes is medically well recognized; however, the exact mechanism remains unknown. The streptococcal trigger and genetic background of psoriasis suggest that psoriasis patients may display a particular, genetically determined sensitivity to streptococcal infection. Streptococcal infection has been found exclusively in type I psoriasis patients. (Please refer to our Blog PSORIASIS – Is it all in the family?) In up to 45% of guttate psoriasis cases, Pharyngitis and upper respiratory infections are the most common trigger recorded. Recent studies suggest that continuing, subclinical streptococcal and staphylococcal infections might be responsible not only for the relapse of acute guttate psoriasis but also for a guttate flare of a new episode of chronic plaque psoriasis as 70%of patients with guttate psoriasis go on to develop chronic plaque psoriasis. 7,8.9,10

Activation of T-cells is considered as an important factor in the pathogenesis of psoriasis, since the laboratory studies have shown that the population of T-cells isolated from the skin of patients with psoriasis is capable of stimulating keratinocytes proliferation. Super antigens, including a group of viral or bacterial proteins, can directly bind to major histocompatibility complex (MHC) class II and the V? component of T-cell receptors, and cause T-cells activation. Recently, much attention has been paid to the role of super antigens as triggering factors in the pathogenesis of psoriasis. Super antigens produced by Staphylococcus aureus are among the most lethal toxins. Toxins of this large family trigger an excessive cellular immune response leading to toxic shock. Some examples of staphylococcal super antigens are staphylococcus enterotoxin A, B, and C (SEA, SEB, SEC), toxic shock syndrome toxin-1 (TSST-I) and exfoliative toxin (ET). Staphylococcal super antigens (SAg’s) play role in the pathogenesis of inflammatory skin diseases. Severity of PS is significantly correlated to enterotoxin production of the isolated S. aureus strains. 11

Infectious perianal dermatitis is in fact a group of diverse diseases that are characterised by anal and/or peri-anal inflammation in children and rarely in adults. Perianal streptococcal dermatitis (PSD) generally occurs in children between six months and ten years of age and affects boys more often than girls. Although uncommon, PSD has also been reported as being caused by Staphylococcus aureus.  In one study, the incidence was reported to range from one in 218 to one in 2000 pediatric outpatient visits.14 Signs and symptoms in this study included perianal dermatitis (90%), perianal itching (78%), rectal pain (52%), and blood-streaked stools (35%). Intra-family spread has been reported in 50% of possible cases. Children with streptococcal pharyngitis have a 6% anal carriage rate. PSD develops 24 to 48 hours after acute afebrile pharyngitis. Some cases of perianal streptococcal dermatitis in children may be linked to guttate psoriasis.

A study published in 2014, concluded superantigens and toxins from Candida “…may play various roles in the exacerbation and the persistence of psoriasis.” 60% of the psoriasis patients tested positive for Candida versus 20% of the control group in oral tests and 15% of the psoriasis patients tested positive verses 4% of the control group in skin tests. The link between the exacerbation of psoriasis, and skin and/or gut colonization by Candida albicans was further confirmed in another study in 2015. 12,15

The role of Malassezia species in psoriasis is still undetermined, but several reports have associated the lipophilic yeasts with the development of skin lesions in psoriasis, the lipophilic yeast Malassezia furfur has been implicated in the exacerbation of scalp psoriasis.15

It was found that when cell fragments of Malassezia were topically applied to the skin of psoriatic patients, new psoriatic plaques were induced.15 Research has also reported that there is a significant correlation between the presence of Malassezia yeast and the severity of skin irritation in existing psoriatic plaques.16 These findings suggest that there are several mechanisms by which Malassezia yeasts may contribute to exacerbate psoriasis, but still remains unclear whether these microorganisms are able to initiate the development of psoriasis lesions. Psoriasis is also known to have a strong genetic component. Therefore, research has investigated immune reactions in patients with psoriasis. It has been shown that these individuals have immunological responses to both Malassezia yeasts and to proteins derived from them. T cells reactive to the yeasts have been isolated from lesional skin and it has been demonstrated that antibodies to the yeasts are present in serum taken from patients with psoriasis, but not from control subjects. 17

REFERENCES

  • Jain SP, Gulhane S, Pandey N, Bisne E. Human papilloma virus infection and psoriasis: Did human papilloma virus infection trigger psoriasis?. Indian J Sex Transm Dis 2015;36:201-3
  • Shinichi Imafuku, Reiko Naito, Juichiro Nakayama; Possible association of hepatitis C virus infection with late-onset psoriasis: a hospital-based observational study. ; J Dermatol 2013 Oct 21;40(10):813-8. Epub 2013 Aug 21.
  • Mohamed A.E. et al.; Psoriasis; a new marker for Hepatitis C among Egyptian Patients; Int.J.Curr.Microbiol.App.Sci (2015) 4(6): 761-767
  • Ahmad QM, Sameem F, Shah IH. Prevalence of hepatotrophic viruses b&c in psoriasis -A study from kashmir. Indian J Dermatol 2005;50:200-2
  • Zakaria Mahran and Tarek M. Emran. Prevalence of hepatitis C virus infection in patients with chronic plaque Psoriasis in Damietta Governorate. J Am Sci 2015;11(7):130-133
  • Failla V. et al; Childhood Herpes Zoster-Triggered Guttate Psoriasis; The Open Dermatology Journal, 2012, Volume 6
  • Sigurdardottir S. L. et al.; The association of sore throat and psoriasis might be explained by histologically distinctive tonsils and increased expression of skin-homing molecules by tonsil T cells; British Society for Immunology, Clinical and Experimental Immunology, 174: 139–151
  • Bartenjev I. et al.; Subclinical Microbial Infection in Patients with Chronic Plaque Psoriasis; Acta Derm Venereol 2000; Suppl 211: 17-18.
  • Leung D.Y.M., et al; Evidence for a Streptococcal Superantigen-driven Process in Acute Guttate Psoriasis; The Journal of Clinical Investigation, Inc. Volume 96, November 1995, 2106-2112
  • Weisenseel P. et al.; Streptococcal infection distinguishes different types of psoriasis; Downloaded from http://jmg.bmj.com/ on February 7, 2016 – Published by group.bmj.com
  • Atefi et al.; The Rise of Staphylococcal Super Antigens in Psoriatic Patients: A Case-Control Study; Jundishapur J Microbiol. 2014 May; 7(5): e9912.
  • Taheri Sarvtin,et al.; Evaluation of candidal colonization and specific humoral responses against Candida albicans in patients with International Journal of Dermatology. Dec2014,Vol.53Issue12, pe555-e560. 6p.
  • Fakhrozaman Pezeshkpoor et al.; Prevalence of Candida in saliva and skin lesions of Psoriasis Vulgaris patients; Journal of Mycology Research. Vol 2, No 1, March 2015, Page 9-14
  • Abbas Rasi, Nargess Pour-Heidari; Association between Plaque-Type Psoriasis and Perianal Streptococcal Cellulitis and Review of the Literature – Case Report; Arch Iran Med 2009; 12 (6): 591 – 594
  • Prohi? A.; Psoriasis and Malassezia Yeasts; www.interechopen.com; http://cdn.intechopen.com/pdfs-wm/32471.pdf
  • Baroni A. et al.; Possible role of Malassezia furfur in psoriasis: modulation of TGF-b1, integrin, and HSP70 expression in human keratinocytes and in the skin of psoriasis-affected patients; J Cutan Pathol 2004: 31: 35–42
  • Zomorodian et al.; Malassezia isolated from psoriasis patients; J Cutan Pathol 2008 doi: 10.1111/j.1600-0560.2007.00968.x
  • Gomez-Moyano E, et al. Do Malassezia species play a role in exacerbation of scalp psoriasis?. Journal De Mycologie Médicale (2014), http://dx.doi.org/10.1016/j.mycmed.2013.10.007