Candida albicans is a yeast that is sometimes found as part of the body’s flora, especially in the gastrointestinal tract. It acts as an opportunist, taking hold in the skin when there is a suitable warm moist environment such as in nappy rash or intertrigo in obese individuals.

The flexural areas affected are red with a rather ragged peeling edge that may contain a few small pustules. Small circular areas of erythema or small papules and pustules may be seen in front of the advancing edge (satellite lesions). Candida may also affect the moist interdigital clefts of the toes and mimic tinea pedis. In people who have their hands immersed frequently in water (e.g. cleaners, nurses) Candida may cause infection in the macerated skin of the finger web spaces or the damaged skin around the nail folds (’chronic paronychia’). Nail infection may mimic tinea unguium. It can infect mucosal surfaces of the mouth or genital tract. This tends to occur in patients taking broad-spectrum antibiotics (due to suppression of protective bacterial flora) or in immunosuppressed patients. Clinically superficial white or creamy pseudomembranous plaques appear which can be scraped off leaving raw areas underneath.

Treatment

Treatment is aimed at removing any underlying predisposing factor and applying topical antifungal creams, e.g. clotrimazole or miconazole (or the equivalent as mouth lozenges/pessaries). Candida nail infections require systemic antifungal therapy with an imidazole such as itraconazole (100 mg daily for 3 months). Recurrent candidiasis is relatively common, especially in women. Diabetes mellitus should always be excluded. Repeated topical treatment or an oral imidazole may be needed.

The history should aim to elicit the following points:

• time course of rash
• distribution of lesions
• symptoms (e.g. itch or pain)
• family history (especially of atopy and psoriasis)
• drug/allergy history
• past medical history
• provocating factors (e.g. sunlight or diet)
• previous skin treatments.

Examination entails looking at and feeling a rash (for terminology, see Table 23.1). It should include an assessment of nails, hair, and mucosal surfaces, even if these are recorded as unaffected. The following terms are used to describe distribution: flexural, extensor, acral (hands and feet), symmetrical, localized, widespread, facial, unilateral, linear, centripetal (trunk more than limbs), annular and reticulate (lacy network or mesh like).

Investigation.

With regard to investigation, clinical acumen remains the most useful tool in dermatology but a variety of tests are useful in confirming a diagnosis.

Table 23-1. Morphological description of skin lesions

Atrophy	Thinning of the skin
Bulla	A large fluid-filled blister
Crusted	Dried serum or exudate on the skin
Ecchymosis	Large confluent area of purpura (’bruise’)
Erosion	Denuded area of skin (partial epidermal loss)
Excoriation	Scratch mark
Fissure	Deep linear crack or crevice (often in thickened skin)
Lichenified	Thickened epidermis with prominent normal skin markings
Macule	Flat, circumscribed non-palpable lesion
Nodule	Large papule (> 0.5 cm)
Papule	Small palpable, circumscribed lesion (< 0.5 cm)
Petechia	Pinpoint-sized macule of blood in the skin
Plaque	Large flat-topped, elevated, palpable lesion
Purpura	Larger macule or papule of blood in the skin which does not blanch on pressure
Pustule	Yellowish white pus-filled lesion
Scaly	Visible flaking and shedding of surface skin
Telangiectasia	Abnormal visible dilatation of blood vessels
Ulcer	Deeper denuded area of skin (full epidermal and dermal loss)
Vesicle	A small fluid-filled blister
Weal	Itchy raised ‘nettle rash’-like swelling due to dermal oedema

Most lymphocyte maturation and activation occurs within the lymphoid tissue/organs located throughout the body. Populations of lymphoid cells of different types originate from pluripotent stem cells in the bone marrow. Immature B lymphocytes remain in the bone marrow to mature. Lymphoid precursors destined to be T cells move to the thymus for maturation. These are termed the primary lymphoid tissues. Once cells have matured, they are released into the circulation and populate secondary lymphoid tissue such as lymph nodes, tonsils and spleen where they are ready to respond to foreign antigens.

Mucosa-associated lymphoid tissue (MALT)

Lymphoid tissue is frequently found in mucosal surfaces in non-encapsulated patches. This is termed mucosa-associated lymphoid tissue (MALT), consisting of genitourinary and gut-associated lymphoid tissue (GALT, mainly Peyer’s patches), bronchus-associated lymphoid tissue (BALT, found in the lobes of the lungs along the main bronchi) and skin-associated lymphoid tissue (SALT).

B cells

These cells comprise approximately 25% of lymphocytes. In response to antigen binding to the B-cell receptor (BCR) and usually with T-cell help, B cells divide and are activated to become plasma cells which secrete large amounts of antibody.

Antibody molecules (immunoglobulins)

Antibodies are glycoproteins. They consist of two heavy chains and two light chains (either κ or λ polypeptides). The heavy chain determines the antibody isotype or class, i.e. IgG, A, M, D or E. The major regions of immunoglobulin are as follows:

Variable ‘V’ domains have variation in the amino acid sequence between immunoglobulins, with short segments of hypervariable regions. Antigen binding occurs in the area where the loops bearing the hypervariable regions of the light and heavy chains come together, called the Fab (fragment antigen binding) region. The shape of the binding site determines the ‘goodness of fit’ or affinity/avidity of any particular antibody for an antigen.

Idiotypes are markers found in the hypervariable region and are associated with the antigen-binding site. The idiotype is antigenic, and idiotypes and anti-idiotypes are thought to make a network regulating the production of antibody.

The Fc (fragment crystalline) region is formed from the constant domains in which the amino acid sequences are relatively conserved. This is the part that binds to cell-surface immunoglobulin receptors (FcR) or causes complement fixation; hence it controls the effects of the antibody molecule after it has bound its antigen.

Genetics of antibody production

Rearrangement of the germline DNA occurs within immature B cells in the bone marrow, leading to production of antibodies with many different antigen-binding sites or clonal diversity. There are three main areas of the gene called the variable (V), diversity (D) and joining (J) regions which need to be spliced together to form the final sequence from which protein will be transcribed to form the antibody molecule. It is during this splicing that much of the variability occurs. Firstly, there is a multiplicity of all these regions within the DNA (V = 25-100 genes, D = 10 genes and J = 5-6 genes). Any one of the multiple genes within a region can join any other (called combinational freedom) to form the final VDJ sequence. Secondly, splicing of the genes together is frequently inaccurate and ‘frame-shift’ in base-pairs leads to misreading and production of the ‘wrong’ amino acid (junctional diversity). Thirdly, somatic mutation in the genes may occur during cell division.

Once the VDJ region is spliced it combines successively to the IgM, IgD, IgG, IgA, and IgE constant genes to cause progressive switching in the isotype of the antibody. However, as the Fab gene is not further altered the same antigen-binding region is maintained. Thus, a mature but naive B cell that has rearranged its VDJ gene will initially make an IgM response on antigen stimulation, as this is the first to be translocated. The primary immune response is therefore of the IgM isotype with IgG and other isotype responses developing later and usually requiring additional T-cell help (T-independent responses are restricted to polysaccharide antigens and usually do not progress from the IgM isotype). However, once the ’switch’ from IgM to another isotype has occurred, memory B cells remain in the body for many years. These react rapidly to any re-challenge with the same antigen, and the characteristic IgG production of the secondary or late primary response occurs. Knowledge of the timing of primary and secondary antibody responses is used in the serological diagnosis of infections, the presence of IgM suggesting acute infection.

The dermis is of mesodermal origin and contains blood and lymphatic vessels, nerves, muscle, appendages (e.g. sweat glands, sebaceous glands and hair follicles) and a variety of immune cells such as mast cells and lymphocytes. It is a matrix of collagen and elastin in a ground substance.

The sweat glands

Eccrine sweat glands are found throughout the skin except the mucosal surfaces.
Apocrine sweat glands are found in the axillae, anogenital area and scalp and do not function until puberty.
The sweat glands and vasculature are involved in temperature control.

The sebaceous glands

These are inactive until puberty. They are responsible for secreting sebum or grease onto the skin surface (via the hair follicle) and are found in high number on the face and scalp.

Nerves

The skin is richly innervated. These fibres allow sensation of touch, pain, itch, vibration and change in temperature.

Hair

Hairs arise from a downgrowth of epidermal keratinocytes into the dermis. The hair shaft has an inner and outer root sheath, a cortex and sometimes a medulla. The lower portion of the hair follicle consists of an expanded bulb (which also contains melanocytes) surrounding a richly innervated and vascularized dermal papilla. The hair regrows from the bulb after shedding.

There are three types of hair:

• terminal – medullated coarse hair, e.g. scalp, beard, pubic
• vellus – non-medullated fine downy hairs seen on the face of women and in prepubertal children
• lanugo – non-medullated soft hair on newborns (most marked in premature babies) and occasionally in people with anorexia nervosa.

All hair follicles follow a growth cycle: anagen (growth phase), catagen (involution phase), telogen (shedding phase). At any one time most hairs (> 90%) will be in the anagen phase, which is typically 3-5 years for scalp hair.
Grey hair is due to decreased tyrosinase activity in the hair bulb melanocytes. White hair is due to total loss of these melanocytes.

Nails

Nails are tough plates of hardened keratin which arise from the nail matrix (just visible as the moon-shaped lunula) under the nail fold. It takes 6 months for a finger-nail to grow out fully and 1 year for a toe-nail.

The subcutaneous layer

The subcutaneous layer consists predominantly of adipose tissue as well as blood vessels and nerves. This layer provides insulation and acts as a lipid store.