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Rosacea--psycho-dermatologic approach.

INTRODUCTION

It is well known that by the aesthetic impact of skin lesions dermatologic disorders can significantly affect the quality of life and mental health of the patient. For many patients, the impact of psychiatric comorbidities is sometimes more important than that of the underlying skin disorder, sometimes with less visible signs. The psychological impact of skin disorders was considered so important that tools to measure quality of life and its changes under the influence of diseases have been developed.

Thus, psycho-dermatology has become a field of interest, which connects two specialties, psychology and dermatology, covering all aspects of how the mind and body interact in relation to the onset and progression of various skin disorders. This interaction occurs in certain skin disorders, such as rosacea, even after the disease onset and throughout the disease course, especially in chronic diseases (1).

Most psycho-dermatologic disorders can be classified into four categories:

* Psycho-physiological disorders: skin disease is exacerbated by psychological factors, such as stress. Some examples in this category are atopic dermatitis, psoriasis, acne, rosacea, lichen simplex, lichen planus, hyperhidrosis. In most patients there is a clear and chronological association between stress and exacerbation, but there may be patients in which mental status does not influence the progression of skin disease.

* Primary psychiatric disorders: diseases in which skin lesions are self-inflicted. In these patients the clinical manifestations are primitively cutaneous, but are a reflection of psychiatric disorders. These include: neurotic excoriations, trichotilomania, illusory parasitosis, dermatitis artefacta.

* Secondary psychiatric disorders: patients with psychiatric manifestations caused by disfiguring skin diseases: vitiligo, alopecia areata, nodular cystic acne.

* Sensory skin diseases: patients complain of burning, stinging, and itching sensations and pain that may not be associated with a skin condition in the absence of an associated mental illness.

This classification of psycho-dermatologic diseases is extremely useful to both dermatologists and psychiatrists for an adequate approach of the patient and initiation of a correct treatment plan, to which the patient to adhere in order for the outcome to be favourable.

CLINICAL FEATURES

Rosacea is a skin disease lacking an entirely satisfactory definition. It is a very common disease, accounting for about 1-3 % of the new skin disease cases diagnosed each year.

Rosacea is a chronic inflammatory dermatitis, which predominantly affects females aged 35-50 years, and rarely seen in adolescents and the elderly. The lesions are located predominantly in the central region of the face, are polymorphous (erythema, telangiectasia, papules, pustules, nodules, etc.) and evolve in successive stages. In some cases the lesions may be located on the scalp, trunk (upper region) and the neck. Despite its benign character, rosacea may be the source of important aesthetic damage. This aesthetic damage underlies the major psychological impact the disease has on patients and significant changes in their quality of life.

The National Rosacea Society, the largest organization in the world dedicated to improving the lives of patients with rosacea, based in the United States, defined and classified rosacea into 4 subtypes: erythematotelangiectatic, papulopustular, phymatous and ocular (1).

The role of digestive, endocrine, infectious, psychological-emotional and vasomotor factors is frequently discussed. However, the association of vascular lesions with inflammatory lesions and the stadial progression are universally accepted.

Although the exact pathogenesis of rosacea is unknown, various theories have been proposed over the years. (3) Among the possible causes, were included defects of the immune system, nervous systems, and facial blood vessels as well as microbial colonization --Demodex folliculorum, Propionibacterium acnes (commensal in the pilosebaceous follicle) and Bacillus oleronius. It has also been suggested that this condition may be inherited and genetic studies are now in progress (4).

Today, research on rosacea has increased significantly, resulting in a growing number of scientific information.

The main possible theories include:

* immunological theory;

* genetic theory.

Other theories:

* involvement of the neurovascular system;

* involvement of vascular changes;

* role of Demodex folliculorum.

Mark et al. (1,3) believe that at the basis of the characteristic rosacea changes is the destruction of the dermal connective tissue (often caused by sun exposure). Other theories include: an abnormality of the blood vessels, characterized by hyperreractivity determined by over expression of endothelial growth factor receptor (VEGFR), which would initiate inflammatory and vascular changes (3) leading to increased skin sensitivity and reactivity to heat; changes in oxidoreduction processes with a decrease in superoxide dismutase levels, not yet known if it is the cause or effect of the inflammatory reaction, but revealed by the efficient use of such antibiotics as tetracycline, metronidazole, azithromycin with important antioxidant properties; high levels of cathelicidin (endogenous antimicrobial peptide), which promotes angiogenesis and leukocyte chemotaxis, being a trigger factor for inflammatory phenomena (3).

Despite the conflicting results, many recent studies correlate rosacea with gastroenterological and chronic gallbladder disorders. Responsibility is attributed to the presence in the stomach of Helicobacter pylori, a gram-negative bacillus associated with chronic gastritis, gastric ulcer and gastric cancer. Arguments in favour of this theory are the detection of Helicobacter pylori by histological examination of antral mucosal biopsy in a large percentage of patients with rosacea, serological detection of antibodies to Helicobacter Pylori (IgG, IgM, IgA), and the simultaneous therapeutic efficacy of metronidazole administered orally for rosacea and Helicobacter Pylori (4,1).

The subjects who develop rosacea are certainly constitutionally predisposed. Primitive cephalic vascular abnormalities involve changes in physiological venous drainage, with reversal of blood flow from the facial vein into its collaterals in the conditions of cerebrovascular hyperthermia. These changes lead to vascular stasis with vascular dilations that, initially, have a paroxysmal character, "flush". Their occurrence is favoured by the ingestion of alcohol and hot liquids, stress or sun exposure. Also involved in flushing are enkephalins, endorphins, bradykinins, their release being stimulated by adrenalin (8). Flush-type lesions are characteristic to the erythematotelangiectatic stage, being associated with spider veins. Another change found in rosacea patients is the elevated blood levels of substance P, substance with a vasodilator role (6).

In the papulopustular stage, the pathogenic mechanisms are less known. The role of infectious factors is controversial, these factors not being considered essential in the causation of rosacea. The role of Demodex folliculorum, commensal mite of the pilosebaceous follicle, has long been debated; it would promote inflammation by mechanical blockage of follicles. Although detected by cutaneous parasitological examination in a large number of subjects diagnosed with rosacea (4), currently its etiologic role is controversial. In the serum of patients with rosacea anti-collagen and antinuclear antibodies (6) were detected, the involvement of an inflammatory immune reaction being increasingly discussed. Another argument would be complement and immunoglobulin deposits at the dermoepidermal junction with a lupus band-like appearance on direct immunofluorescence (6,8), the presence of lesions characterized by granulomatous inflammatory infiltrates, determined by epithelial debris, especially in advanced stage skin lesions.

Clinical signs suggestive for the diagnosis of rosacea are: erythema, telangiectasias, papules, pustules, scales, and granulomatous lesions. Over time, the clinical behaviour of dermatosis is suggestive and consists in cyclical course influenced by patient's eating habits, psychological state and sun exposure, with sudden episodes of eruption and even periodic improvements. Another important diagnostic feature is the progressive nature of eruption. Onset is characterized by a transient congestive dermatosis (paroxysmal flush) followed by a remarkable stability of the lesional context (couperose/telangiectasia and papulopustular lesions) (7) progressing to granulomatous and even phymatous lesions (especially in men) (5,6).

Papular lesions may become nodular in the severe forms of rosacea, with appearance of lupoid infiltrate on vitropression. Skin edema may accompany or follow the episodes of papulopustular eruption. The eruption is commonly located symmetrically on the convexities of the central face, forehead, cheeks, nose, chin, and rarely on the cervical region, areas of scalp alopecia, forearms or legs. During the stage of tissue hyperplasia, the skin has an inflammatory, swollen appearance, with enlarged pores and associated with connective tissue hypertrophy and hyperplasia of sebaceous glands give the face an irregular appearance. The affected areas are the cheeks, nose, central face, with a major aesthetic impact (4).

The particular types of rosacea are often seen in clinical practice, but their true incidence is not correctly quantified.

Ocular rosacea (ophthalmic rosacea): the incidence of this clinical form is differently estimated by the various authors, ranging from 3 % to 50 %. Ocular manifestations are of inflammatory type (8) and range from minor (conjunctivitis, iritis, blepharitis, episcleritis) to major complications (iridocyclitis, keratitis, corneal ulcers and corneal opacity).

Hyperplastic rosacea: it is considered an advanced, severe form of rosacea, described in a small number of patients. Characteristic is the progressive occurrence of prominent inflammatory nodules with tissue and sebaceous hyperplasia, predominantly on the nose (rhynophyma), chin (gnatophyma) and auricular pavilions (otophyma). The skin is purple, with venous ectasias and dilated pillar orifices through which sebum and cellular debris are removed. This stage is more common in males and was associated with chronic alcohol use (8), but, at present, there is no supporting evidence in this regard.

Granulomatous or lupoid rosacea: is characterized by multiple brown-red papules or little nodules on a diffusely erythematous and edematous skin with chronic course. It frequently involves the lower eyelids, perioral area or hairy skin of the scalp. The small nodular type of sarcoidosis, contact eczema, or perioral dermatitis should be excluded, the clinical differential diagnosis being extremely difficult. This clinical form is associated in a significant number of cases with haemorrhagic rectocolitis (6).

Rosacea conglobata: is a severe form of rosacea that mimics an acne conglobata. The characteristic lesions are indurated plaques and haemorrhagic and purulent nodular abscesses. History of rosacea and topography provide clues to the diagnosis (7). Steroid rosacea: characterized by papulopustular lesions, multiple telangiectasias and atrophy, lesions resulting from the excessive use of topical corticosteroid, exacerbating an already existing rosacea (8).

Lymphedematous rosacea: rare form of rosacea (6) characterized by massive, hard, diffuse edema associated with chronic skin inflammation on the forehead, nose and cheeks.

Rosacea fulminans: controversial and rare entity occurring in young women; it is characterized by nodules that coalesce to form abscesses (4).

The identification of the aggravating factors of rosacea is an individual process. Each patient has to identify what are the causes of skin lesion worsening, since these vary from case to case. This has to be done prior to treatment initiation, their avoidance being the main therapeutic indication. Of the common aggravating factors, we mention: extreme temperatures, wind, hot drinks, soda, alcohol, caffeine, spices, drugs, topical substances and, last but not least, emotional factors (7).

TREATMENT

Treatment has to be adapted to the stage of the disease (6). The first therapeutic indication is to avoid the aggravating factors, whenever possible. Independent of the stage of disease and therapeutic indications, psychological/psychiatric assessment of the patient should be performed before the initiation of treatment, very helpful in this respect being the scoring forms for the quality of life. These scores may be useful for monitoring the treatment and quantify the effects of treatment on the course of the disease.

Treatment of vascular hyper-reactivity (flush) (4)

In this stage of rosacea, the therapeutic goal is to reduce the discomfort caused by paroxysmal erythema, decreasing its intensity and duration. Patients should be informed about the importance of good personal hygiene and healthy lifestyle in obtaining a long-term therapeutic success. Alcohol, spicy foods, emotional upsets, temperature changes and sun exposure should be avoided by the patient with rosacea. Topical vasoconstrictors or systemic administration of substances that could control the circulatory abnormality have a beneficial effect on the vascular component of rosacea (8).

Treatment of couperose includes such therapeutic alternatives as cryotherapy, linear microscarification, dermabrasion, electrocautery, microinjections with sclerosing substances, laser therapy (5).

The first-line treatment of papulopustular rosacea is general and local antibiotic therapy (5).

Local treatment

Topical metronidazole 1 % is an effective molecule and can be used in the treatment of rosacea, but also as a single dose in maintenance treatment. Alcoholic lotions with 3 -5 % resorcinol, 0.3 % vitamin A acetate or 2 % erythromycin cream can also be used (4,5). General treatment

General treatment includes second-generation tetracyclines (minocycline, doxycycline) which have a good tolerance when administered for several weeks, and have a role in the prevention of eye involvements. In case of intolerance or ineffectiveness, macrolide (erythromycin, clarithromycin) at average doses and in repeated courses may be prescribed (5,6).

Metronidazole is effective but poorly tolerated during long-term treatment, thus topical administration is preferred. In subjects diagnosed with Helicobacter pylori, the use of metronidazole 250 mg twice daily for a month, then 250 mg/day for another month followed by 125 mg/day for 2-4 months has beneficial effects.

Isotretinoin is not typically used in rosacea, and it is most commonly used in the treatment of severe forms (granulomatous rosacea, rosacea conglobata or fulminans); it is administered in minidoses of 2.5 mg/day for about 6 months, but with close monitoring of its side effects (eye disturbances, angiogenesis stimulation, changes in serum transaminases). Also in severe forms (lupoid, infiltrated), isoniazid 300 mg/day for several weeks and in rosacea conglobata isotretinoin combined with short courses of corticosteroids can be used (4).

Rhynophyma is a rare clinical form of rosacea with major psychological impact. Treatment is essentially surgical or cryosurgical and is indicated in cases of hyperplasia, obtaining the remodelling of the nasal pyramid. Other used methods are cryotherapy combined with electrocoagulation or argon laser photocoagulation. Preoperatively, patients may receive treatment with systemic retinoids at a dose of 0.5 mg/kg/day to reduce sebaceous gland hyperplasia.

PSYCHIATRIC APPROACH OF THE PATIENT WITH ROSACEA

It is well known that most skin diseases have significant comorbidities, requiring a comprehensive approach of the patient. Stress is one of the etiological/trigger factors most frequently involved in dermatological diseases, reason why assessing the impact of the disease on the quality of life has become one of the mandatory instruments for assessing the severity of a disease, but also for monitoring the course of the disease or therapeutic outcomes (7).

An instrument for assessing the impact of the rosacea on patient's quality of life is Dermatology Life Quality Index Questionnaire (DLQI) (7). It has long been used in dermatology, being one of the instruments that serve to quantify the severity of atopic dermatitis and psoriasis. Patients with rosacea may suffer from depression or anxiety, and the presence of these psychiatric conditions is a reason for referral to a mental health professional. Loss of self-confidence and self-esteem are red flags that must be noticed by the dermatologist in view of initiating an adequate therapy (1). The dermatologist does not have the arsenal required for treating mental illnesses, but can refer the patient to a psychiatrist or psychologist for receiving an appropriate treatment. Unfortunately, some of these patients may refuse to see a psychiatrist because of the perceived stigma (2). Dermatologists are concerned with the course of skin lesions, while patients with how the disease affects their everyday life, social functioning and family life.

Nicholson et al. developed a questionnaire for assessing the quality of life of patients with rosacea called RosaQuel which proved to be an invaluable tool for monitoring patients with rosacea. Although rosacea is considered only a cosmetic problem, the incidence of psychiatric comorbidities (depression being the most important) requires a change in attitude towards this disease (7).

DISCUSSIONS

In the past diseases, such as rosacea, urticaria, eczema were thought to be sometimes caused by stress, the result of "damage to the nervous system, as a manifestation of emotions, especially those of depressive type" (1).

The term psychosomatic disorder refers to a physical disease caused or aggravated by psychological factors. In the case of dermatological conditions, such as rosacea, psoriasis, lichen planus etc., there is a proven relationship between somatic dermatological disease and psychological status of the patient, especially correlated with the flare-ups.

Dermatologists should refer patients with psychosocial needs to a psychiatrist or psychologist, because these manifestations are as important as the somatic ones (1). The use of questionnaires measuring quality of life can be an easy way to identify the impact of the disease on mental status and to monitor disease progression during treatment.

Many skin diseases are chronic and incurable. The psychological impact on the patient is subjective and individual, thus it cannot be generalized. The impact on the quality of life is complex, unpredictable, and plays a major role in treatment decision. Approximately 30 % of patients have at least one psychiatric comorbidity related to the fear of disfigurement (dysmorphophobia), excessive handling of skin lesions, intentional or not, social anxiety, social phobia (1).

Associated to social phobia, an increased incidence of depression was found. Studies in large cohorts of patients (2) showed that 76 % of patients experienced diminished confidence and self-esteem, 69 % felt ashamed of their physical appearance, 65 % felt frustrated, 50 % lost hope for the better, 41 % suffered from anxiety, 38 % used to cancel social activities because of their physical appearance, 35 % felt hopeless, 25 % had depression, 18 % feel isolated from entourage and society. Other psychosocial implications are represented by career (especially in patients with public service professions) and sex life (3).

Besides DLQI, one of the most commonly used instruments in dermatology patients, other instruments that can detect the emotional aspects determined by the sometimes disfiguring lesions of rosacea are available. Among these, we mention Body Image Avoidance Questionnaire, Appearance Schemas Inventory and Derriford Appearance Scale (7). Although these questionnaires can be adapted for use in dermatology, they have not yet been approved for clinical dermatology practice.

Thus, studies showed a mild to moderate impairment of quality of life (score 4 to 7.8). To be more specific, a 21-item questionnaire, called RosaQol, was developed to provide information related skin lesions, need to cover them, feelings of shame, frustration, concern for the side effects of medication, etc.

CONCLUSIONS

The patient with rosacea is a multidisciplinary patient, but the main involved specialties are dermatology and psychiatry/psychology.

Because skin lesions are mainly located on central face, the aesthetic impact is major resulting in significant change in quality of life. Skin lesions may cause significant mental changes, determining decreased self-esteem, anxiety, depression, tendency to isolation. Emotional stress can be considered both a trigger factor and a consequence of rosacea lesions. Thus, when patients feel stressed about their condition, it can aggravate or maintain their skin lesions and lead to a further decline in their emotional state, which becomes a vicious cycle. Given these circumstances, the patient with rosacea should benefit from a complex treatment, both dermatological and psychological counselling. For a complete treatment, especially in patients with inflammatory, phymatous lesions, psychological counselling is essential.

A correct treatment will improve the quality of life of patients with rosacea. This parameter can be measured using specific instruments that can be used both initially to determine the stage of disease and its severity and during the disease course to assess the effectiveness of treatment, disease restaging, etc.

When a dermatologist has to treat diseases like rosacea, he/she should keep in mind that treatment should address both the physical manifestations and the mental and social consequences and profound impact on the quality of life. The psychological problems of patients should not be minimized because they may be a major aggravating factor. Appropriate and timely psychiatric approach, timely and discussing the issues with the patient can be essential for an adequate management of patients with rosacea. This approach may increase patient adherence with the prescribed therapy, and thus lead to a favourable course of the disease.

Laura STATESCU--M. D., Ph. D., Dermatologist at "St. Spiridon" Emergency Hospital Iasi, No. 2 str. Vasile Conta; teaching assistant at "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Department of Dermatology, Iasi, Romania

Dan VATA--M. D., Ph. D. Senior Dermatologist at "St. Spiridon" Emergency Hospital Iasi, No. 2 str. Vasile Conta; lecturer at "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Department of Dermatology; E-mail: dan.vata@umfiasi.ro, tel.: +40.741.084.264, corresponding author; Iasi, Romania

Alina STINCANU--M. D., Dermatologist at "St. Spiridon" Emergency Hospital Iasi, No. 2 str. Vasile Conta, Iasi, Romania

Laura GHEUCA SOLOVASTRU--M. D., Ph. D., Senior Dermatologist at "St. Spiridon" Emergency Hospital, No. 2 str. Vasile Conta; Professor at "Grigore T. Popa" University of Medicine and Pharmacy Iasi, Department of Dermatology, Iasi, Romania

ACKNOWLEDGEMENT AND DISCLOSURE

The authors have no potential conflict of interests to disclose.

REFERENCES

(1.) Millard, L. G., Millard, J. Psychocutaneous Disorders in Tony Burns, Stephen Breathnach, Neil Cox and Christopher Griffiths Editors, Rook's Textbook of Dermatology, Vol. 1, Eighth Edition, Blackwell Publishing, 2010, pp. 64.1-64.55.

(2.) Lee, C. S., Accordino, R., Howard, J., Koo, J. Psychopharmacology in dermatology. Dermatologic Therapy, Vol. 21, 2008, 69-82.

(3.) Berth-Jones, J. Rosacea, Perioral Dermatitis and Similar Dermatoses, Flushing and Flushing Syndromes in Tony.

(4.) Burns, Stephen Breathnach, Neil Cox and Christopher Griffiths Editors. Rook's Textbook of Dermatology, Vol. 1, Eighth Edition, Blackwell Publishing, 2010, pp. 43.1-43.11.

(5.) Gheuca Solovastru, L., Vata, D., Statescu, L., Andrese, E. The psychiatric burden of chronic dermatological diseases, Bulletin of Integrative Psychiatry, 2014.

(6.) Kupiec Banasikowska, A., Singh, S. Rosacea, http://emedicine.medscape.com/article/1071429-overview

(7.) Powell, F. C., Raghallaigh, S. N. Rosacea and Related Disorders in Bolognia, J. L., Jorizzo, J. L., Schaffer, J. V. Editors, Dermatology, Vol. 1, Third Edition, Elsevier Limited, 2012, pp. 561-570.

(8.) Zouboulis, C. C., Katsambas, A. D., Kligman, A. M. Pathogenesis and Treatment of Acne and Rosacea, Springer-Verlag Berlin, Heidelberg, 2014.

(9.) Petrescu, Z., Branisteanu, D. E., Taranu, T., Statescu, L., Statescu, C. Dermatologie si infecfii transmise sexual. Ed. Junimea, Iasi, 2008:318-327.

(10.) Picardi, A., Pasquini, P., Abeni, D., et al. Psychosomatic assessment of skin diseases in clinical practice. Psychother Psychosom. 2005;74:315-22.

(11.) Garnis-Jones, S. Psychological aspects of rosacea. J Cutan Med Surg. 1998;2:S4-S16.

(12.) Drake, L. Rosacea Review. The National Rosacea Society Newsletter: Winter; 2005. http://www.rosacea.org

(13.) Nicholson, K., Abramova, L., Chren, M. M., et al. A pilot quality-of-life instrument for acne rosacea. J Am Acad Dermatol. 2007;57:213-21.

Correspondence:

Dan VATA

M. D., Ph. D., Senior Dermatologist

"ST. SPIRIDON" EMERGENCY HOSPITAL IASI

Lecturer at "GRIGORE T. POPA" UNIVERSITY OF MEDICINE AND PHARMACY IASI

Dermatology Department, Iasi, Romania

Tel.: +40 741 084 264

E-mail: dan.vata@umfiasi.ro

Submission: August, 31st, 2015

Acceptance: November, 2nd, 2015
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Author:Statescu, Laura; Vata, Dan; Stincanu, Alina; Solovastru, Laura Gheuca
Publication:Bulletin of Integrative Psychiatry
Article Type:Report
Date:Dec 1, 2015
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