Inflammatory skin diseases

1. Layers of the host defense system

The host defense system of the skin is mainly composed of the following three layers: (1) barrier of the skin, (2) innate immunity, and (3) acquired immunity [1]. In general, these layers are aligned in this order chronologically, functionally, and phylogenetically. A disorder in a specific layer can arise from defects in the superior layer. Each layer has unique roles to protect the body against specific infectious agents and external/internal dangers. Inflammation is defined as a series of protective and regenerative responses of the body. Therefore, inflammatory skin diseases are originally a result of these protective and regenerative responses of the skin against infections and dangers. If primarily causative infections and dangers are ruled out, the dermatitis is due to hereditary or acquired disorder in a specific layer of the host defense system.

Descriptive dermatology of the morphological phenomena of skin has been developed for more than two thousand years. Despite recent and ongoing progress in immunology, innate immunity, and the skin barrier, inflammatory skin diseases have not yet been fully classified in terms of the defects in each layer of the host defense system.

In this review, we propose a new algorithm to understand the pathology of inflammatory skin diseases in terms of the specific roles of each three layer in host defense system of the skin (Box). We describe the disorder of these layers in reverse order from acquired immunity to barrier, for the better understanding (see Section 5).

2.1. Immunodeficiency

A number of hereditary diseases have been identified as a genetic lack of the specific molecules that are essential in acquired immunity. Many of them are associated with a variety of cutaneous infections and inflammation. For example, X-linked agammaglobulinemia (XLA) develops furunculosis, impetigo, and atopic-like eczematous eruptions. X-linked lymphoproliferative (XLP) disease is highly accompanied by infectious mononucleosis due to Epstein–Barr virus (EBV) infection. Chronic mucocutaneous candidiasis (CMCC) is composed of heterogeneous diseases, some of which have molecular defects in the acquired immunity, such as defects in the autoimmune regulator (AIRE) gene (see Section 2.3.1) [2]. Acquired immunodeficiency syndrome (AIDS) patients are highly susceptible to fungal and herpes virus infection, such as human herpes virus 8 (HHV8), and patients develop repetitive and severe herpes and Kaposi’s sarcoma in the skin.

Skin diseases and people’s health

In modern society, more and more people are attacked by a variety of diseases. In medicine, relevant skin diseases seriously affect people’s health. As one of the common diseases, skin diseases such as leprosy, scabies, fungal disease, bacterial skin infections appear frequently. With the form, structure and functions changing, skin (including hair and armor) is influenced by external and internal factors, which produce the pathological process, and the corresponding produce all sorts of clinical successively performance. This is the cause of skin diseases. They have a high incidence of dermatitis, but relatively the symptoms are not serious, they often do not affect health, but a few heavier are even life-threatening.

As a typical kind of skin diseases, photodermatoses are among the most common skin disorders in the world. Some of them acquired a particular importance in some regions because of their high frequency, severity, and also be­cause of their different diagnostic and therapeutic ap­proaches.

Photo medicine is a rapidly developing subspe­cialty of dermatology concerned with skin diseases caused by radiation in the UV and visible spectra. Initiation or exacerbation of a rash after sun exposure that occurs in typical light-ex­posed areas is features that point toward a sun­light-induced condition. The diagnosis of photosen­sitive conditions may be difficult, and the use of investigations such as light, patch, and photopatch testing may be necessary to confirm the diagnosis. [1]

Background and history

With the development of modern medicine, every Teaching Hospital Department is in treat­ment development dilemmas. For becoming involved in a new therapy, they still need to promise to be at the speculative stage. In the early 1990s, the problem about whether to actively become involved in the development of PDT for skin cancers was discussed by the Photobiology Unit within the Department of Dermatology in Dundee. As a new invest significant re­sources, it’s so difficult for PDT to have a fairly certain outcome. By 1998, with the position changed and enough good quality data existed, treatment outcomes justi­fied become involved in the development of both PDT and photodiagnosis (PD) for pre-malignant and malignant skin lesions. From a clinical re­search and therapeutic point of view, the skin has two huge advantages. Firstly, it can be easily ex­amined with the naked eye, and secondly, it is the most accessible organ for investigation, biopsy and treatment. Although PDT firmly has its roots at the beginning of the last century, it is only over the last 15 years that it has gained considerate popularity as a topical treatment of great promise for the treatment of skin cancers.[2]

In 1900 a German medical student Oscar Raab famously reported the concept of cell-induced death subsequent to light interacting with chemicals. In subsequent exper­iments he demonstrated that this effect was greater that with alcidine red alone, light alone or alcidine red exposed to light and then added to the paramecium. He postulated that in vitro toxicity occurred as a result of fluorescence caused by the transfer of energy from the light to the chem­ical. Professor von Tappeiner soon after predicted the future of fluorescent substances in medicine.

In 1904 von Tappeiner and Jodlbauer identified that oxy­gen was integral component in photosensitisation reactions and termed the phrase ”photodynamic action” in 1907. Since its incidental discovery in 1900 photodynamic ther­apy (PDT) and all aspects relating to it from mechanism of action, differing photosensitisers through to clinically based applications have been studied. Three components are required for PDT to occur; a photosensitiser, oxygen and a light source. [3]

The Photobiology Unit (photobiology = the study of tight on living systems) has the purpose in Scotland of diagnosing tight sensitive skin disease (the photodermatoses) and the development of new forms of tight therapy (phototherapy). This Centre, which has been in existence since 1973, has always combined clinical skills (photodermatology) with a strong scientific base (photophysics) and laboratory biology (photobiology). This combination of applied science and clinical service in the same unit has pro­vided exciting research opportunities. Applied photo physics, through the Medical Physics Department, has dedicated members of staff whose only rote is optical physics. The necessary expertise in tight de-tivery and measurement is essential for predictable PDT and PD.

Basic knowledge of sun and the skin

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Visible light

Figure 1 the place of ultraviolet radiation in the electromagnetic spectrum

Figure 1 illustrates the relationship between ultraviolet radiation and the other types of non-ionizing radiation, such su natural light an infra-red radiation. It will be seen that ultraviolet radiation from the sun is divided into three different wavelengths-UVA, UVB, and UVC. The UVA waves are the longest and the UVC the shortest.

At present, UVC is prevented from reaching the earth’s surface by the ozone layer, and is not therefore a natural hazard. There is, however, concern that the loss of the protective layer of ozone above the earth’s atmosphere will continue, and that in future more UVB might reach the earth. The main ultraviolet component of travel of natural that does each the earth’s surface is UVB. This penetrates the epidermis and reaches the more superficial layer of the dermis—the papillary dermis. UVA is also present in sunlight and ,in the early spring, a high proportion of natural sunlight in countries at latitudes 50 degrees or more north of south of the equator is composed of UVA. As the summer develops the proportion of UVA falls. UVA is the main, but not the only, wavelength found in the long tubes in UVA sunbeds. The effects of UVA go deeper into the skin than those of UVB. A very simple rule of thumb is that chronic over-exposure to UVB causes wrinkles, chronic over-exposure UVA causes sagging, and chronic over-exposure to both increases the risk of developing skin cancer. One of the important points of difference between UVB and UVA exposure is that acute over-exposure to UVB causes the redness and soreness recognized as sunburn. This is maximal 12-24 hours after the exposure has taken place, and is a useful warning that the skin should be protected for a few days until the redness has disappeared.

The chemicals in sun-screens that protect against UVA and UVB can be divided into those that absorb ultraviolet radiation and those that reflect it away. The absorbing chemicals include para-aminobenzoic acid-PAMA- cinnamates, and salicylates, which protect against UVB alone. Benzophenones protect against both UVB and UVA and are also chemical sun-screeners.[4]


The skin is our main defense against light, and in particular against ultraviolet (UV) radiation. Sometimes the skin reacts abnormally to light by becoming inflamed. This is called photosensitivity.

There are many causes of photosensitivity. Some of the most important are below:

Acute parts like Sunburn Xeroderma pigmentosum, Porphyria, Solar urticaria, Pellagra, and Photosensitivity disorders like Polymorphic light eruption, Juvenile spring eruption, Hydroa vacciniforme, actinic prurigo. Disorders exacerbated by light include Drug reactions, Lupus erythematosus, Rosacea Darier’s disease Eczema (including actinic dermatitis and photo contact dermatitis Psoriasis Lichen planus.

These reactions are either a direct toxic effect of light, or have an immunological component, either provoked by light alone or in conjunction with something else such as a drug.

Diagnosis and treatment of common causes of photosensitivity

The acute effects of sun on the skin are all too familiar. They are caused largely by medium wavelength UV radiation (UVB), but the “dose” required producing sunburn depends on:

(1)An individual’s skin type

(2)The intensity of the radiation (greatest near the equator and around midday)

(3)The length of exposure to UVB

Mild sunburn causes erythema: more severe damage leads to extensive blistering and epidermal boss. Treatment makes little difference to the acute changes, but symptomatic relief can be obtained with soothing lotions, such as calamine. These include avoiding the midday sun, seeking shade, wearing appropriate clothing and eyewear, and using sunscreens, this is more important for those with skin type I and II than for those with a more radiation skin.

There are several special examples which are listed and explained:

(1) Porphyria:

Some forms of porphyria are associated with photosensitivity. In a European child the most common is erythropoietic protoporphyria, whereas an adult presenting for the first time probably has porphyria cutanea tarda. The latter is often associated with alcoholic liver disease. Screening tests involve blood ,urine and stool samples and are best undertaken in a specialist setting.

(2)Solar Urticaria: Rarely, exposure to light leads to urticarial weals.


In western societies, nicotinic acid deficiency is seen most commonly in alcoholics. It presents a triad of changes: Diarrhoea Dementia Dermatitis, which is light sensitive.

(4)Polymorphic light eruption

This is perhaps the most important, and certainly the commonest of the primary photosensitivity disorders. Patients often refer to their skin changes as”prickly heat”, but true prickly heat (or miliaria rubra)is quite different.

Polymorphic light eruption presents a day or two after sun exposure, with changes on light exposed areas, for example the forearms, legs the “V” of the neck and the face. The lesions are itchy and morphologically variable (hence “polymorphic”). There may be papules, plaques, and blisters of areas resembling eczema. They increase in intensity over a week or so before subsiding.

Treatment with topical steroids provides some relief, but some patients require systemic steroids to control an acute attack. Prevention is a better approach. Unfortunately, sunscreens are often not effective, but pre-season PUVA works well and can last for a whole summer. An alternative is the use of antimalarial medication (notably hydroxychloroquine) taken during sunny periods, or while abroad. A variety of polymorphic light eruption occurs almost exclusively in boys. Clusters of small blisters appear on the topes of the ears, especially in early spring. The condition settles spontaneously with age.

Skin Diseases in the Era of Highly Active Antiretroviral Therapy

With the increasing number of HIV-infected patients receiving highly active antiretroviral therapy (HAART), the shift in their dermatologic profile becomes less characteristic of AIDS-defining illnesses.

Retrospective review of mucocutaneous pathology among patients seen at HIV-Dermatology Clinic from January 2009 to December 2013.

Among 534 patients, there were 68.4% males and 31.6% females, with 8.7-year average duration of infection; 82.8% were receiving HAART. Kaposi sarcoma was the only relatively frequent AIDS-defining disease. Fungal and viral infections were common, with human papilloma virus (HPV) as the most frequent overall. Benign and premalignant tumors were associated with HAART and CD4 >200/mm3 (P < .05). Psoriasis was prevalent among patients without HAART (P < .05). Prurigo was associated with lower CD4 count (P < .001).

Patients receiving HAART are faced with chronic skin problems such as benign and premalignant tumors, and HPV infection adds to their neoplastic predisposition. Further research is recommended to develop protocols for treating psoriasis and screening for HPV-associated neoplasia among patients.

Keywords skin diseases, HIV, HAART

Patients living with HIV infection are usually afflicted with skin diseases, and their variability and severity often reflect their level of immune deficiency. Ranging from infections, inflammations, and neoplasms, these can lead physicians to the initial diagnosis of HIV infection or can manifest the various stages of its disease evolution. In addition to this is the problem of drug reactions and iatrogenic effects as well as the reactivation of certain diseases alongside immune reconstitution while receiving highly active antiretroviral therapy (HAART).1

The epidemiologic profile of dermatologic illnesses in relation to HIV varies between countries. This is mainly affected by economic and political factors pertaining to the availability of HAART, as well as the risk-taking behavior of patients. In Portugal, a few years after the recognition of HIV (1985-1991), the mucocutaneous manifestations were dominated by AIDS-defining conditions, such as oropharyngeal candidiasis and Kaposi sarcoma, as well as the aggravation of more common conditions, such as herpes simplex virus (HSV) infection, herpes zoster, dermatophytosis, seborrheic dermatitis, and drug-related skin disorders.2 However, for the past 5 years, there has been a decreasing trend in terms of the number of new HIV-infected cases but with an increasing number of people living with the infection alongside the increasing number of patients receiving HAART.3 These observations result to a less number of opportunistic infections, but instead there is the emergence of medical problems that were less common before4 and a shift to more chronic forms of illnesses.

This study aims to have a descriptive measure of the current epidemiology of mucocutaneous pathology among HIV-positive patients, based on the referrals to the dermatology clinic of a tertiary hospital in Lisbon, Portugal, from 2009 to 2013. By understanding the trend and identifying shifts in the epidemiologic burden of disease, the authors hope to identify areas that can be bases for future research in assessing the economic burden of HIV in the field of dermatology and hence aid in the formulation of new policies and planning of resource allocation.5

Clinical Data

We accessed data from the electronic records of all HIV-infected patients on their first consult at the Specialized HIV Clinic of the Dermatology Service of Hospital de Santa Maria during the period of January 2009 to December 2013. These include in-hospital referrals as well as those referred from other hospitals in Greater Lisbon area. Dermatologic diagnoses were based on clinical data and, if needed, laboratory and pathologic correlations as in the case of malignant neoplasms. The medical ethics board of the hospital approved the study.

Statistical Analysis

The primary outcome variable was the frequency rate of identified skin diseases among the study participants, classified according to those receiving and not receiving HAART. We also determined the mean CD4 count for each diagnosis. The secondary outcome variables were the significant correlation of each diagnosis with the patient’s HAART status and the significant difference in the mean CD4 count among the diagnoses.

We analyzed the data statistically using IBM Statistical Package for the Social Sciences (SPSS) version 22. We used summary statistics, where N is the total number of HIV-infected patients included in the study. For the analysis of the secondary outcome variables, we used Pearson χ2 test (P < .05) to check for correlations between categorical data. For parametric data, we used independent samples t test at the same significance level.

Epidemiologic Profile

We initially assessed a total of 564 patients, of which 5% did not have CD4 count available on record. In the end, we included a total of 534 patients, of which 68.4% were males and 31.6% were females. They were mostly Caucasians with 18% non-Caucasians. The mean age at the time of dermatologic consult was 44.6 years (standard deviation [SD] = 11.9), whereas the mean age at initial HIV diagnosis was 36 years (SD = 11.9), both values with no significant difference between the genders. The average duration of HIV infection was 8.7 years (SD = 6.4). The primary mode of HIV transmission was heterosexual, with 18% being men having sex with men (MSM). History of intravenous (IV) drug use was identified in 21.8%, of which 96.6% were Portuguese and 98.3% were heterosexuals. Also, the majority of the study population had HIV-1, with 3.9% HIV-2, of which 76% were non-Caucasians.

In this study, around 82.8% were receiving HAART at the time of their dermatologic consult. Almost all (96.4%) of them were compliant, with no significant difference between genders. The 3.4% of those who were not compliant were all heterosexuals. In this case, noncompliance was significantly correlated with the history of IV drug use (P < .05).