Hailey-Hailey Disease With Coexistent Herpes Virus Infection: Insights Into the Diagnostic Conundrum of Herpetic/Pseudoherpetic Features in Cutaneous Acantholytic Disorders.

The specific histopathologic diagnosis of a primary acantholytic disorder takes into account the distribution and extent of acantholysis, presence or absence of dyskeratosis, nature of the dermal inflammatory cell infiltrate, and immunofluorescence findings. Herpes virus infection is a common cause of secondary acantholysis where distinctive viral cytopathic changes aid in making it a clear-cut diagnosis in majority of cases. We present a case of coexistence of Hailey-Hailey disease and herpes simplex virus infection to compare and contrast their histopathologic features. This is imperative because acantholytic cells from primary acantholytic disorders may occasionally show cytological features traditionally associated with herpes virus infection (pseudoherpetic changes). The objective of this article is to create a greater awareness of pseudoherpetic changes and also to explore the clinical significance of coexistence of a primary acantholytic disorder and herpes virus infection, as in this case.

Pseudomembranous changes in the dermis: A novel observation and potential clue for evolving lipodermatosclerosis?

Lipodermatosclerosis (LDS) is a well-recognized form of fibrosing panniculitis. Although chronic cases are readily diagnosed, early and evolving lesions may be clinically mistaken for cellulitis and other forms of panniculitis. Most pathologists are familiar with a pseudomembranous type of fat necrosis as a useful feature of chronic LDS. Although nonspecific, this distinctive pattern of fat necrosis helps in supporting a diagnosis of LDS in the appropriate clinical context. The histopathologic features of early and evolving LDS and those involving the dermis are less well documented. We report a case of early LDS showing extensive pseudomembranous changes in the dermis on a superficial skin biopsy where progression to a classic established lesion was documented clinically. We suspect that this previously unreported and unusual finding may be a histopathologic clue for evolving lesions of LDS.

Managing patients with hidradenitis suppurativa.

Hidradenitis suppurativa affects the apocrine-bearing areas of the skin. The onset is variable but usually occurs in the second and third decades of life, coinciding with development of the apocrine glands. The condition is characterised by painful, inflammatory papules and nodules which frequently progress to form abscesses, sinus tracts and hypertrophic scars. Bacteria are not felt to have a primary role in lesion formation, and abscesses are often sterile. The diagnosis of hidradenitis suppurativa is clinically based, without a specific diagnostic test. The most important non-genetic factors implicated in hidradenitis suppurativa are obesity and smoking. Locally recurring lesions can be treated surgically and more widespread disease may be better managed with a combination of medical treatment and surgery.

Tailor systemic therapy to the patient with severe psoriasis.

There is no standard definition regarding the severity of psoriasis, and a number of factors should be considered, including the extent and stability of skin disease, involvement of joints, response to treatment, and impact on quality of life. Erythrodermic psoriasis and pustular psoriasis are severe conditions and the patient may be systemically unwell and febrile. NICE recommends that four key areas should be evaluated and recorded when assessing patients: severity, using the static Physician's Global Assessment (sPGA); disease impact on physical, psychological and social wellbeing using the Dermatology Life Quality Index (DLQI); the presence of psoriatic arthritis; and comorbidities. Ideally, patients should be assessed annually for psoriatic arthritis: the Psoriasis Epidemiology Screening Tool is a validated tool to screen for psoriatic arthritis in primary and secondary care. Patients with severe psoriasis should undergo cardiovascular risk assessment at presentation and every five years, or more frequently if indicated. Referral to secondary care should be made for patients with any type of psoriasis with poor response to topical therapy (after 2 or 3 months according to SIGN) and for extensive psoriasis. Cases where the psoriasis is having a significant physical or psychological impact on an individual's quality of life warrant early referral, as do those where the diagnosis is uncertain. Patients with generalised pustular psoriasis or erythroderma should be referred urgently for same-day specialist input. Patients with acute guttate psoriasis who may require phototherapy should also be referred. Children and adolescents with any type of psoriasis should be referred to a specialist at initial presentation.

Managing actinic keratosis in primary care.

Actinic, or solar, keratosis is caused by chronic ultraviolet-induced damage to the epidermis. In the UK, 15-23% of individuals have actinic keratosis lesions. Risk factors include: advanced age; male gender; cumulative sun exposure or phototherapy; Fitzpatrick skin phototypes I-II; long-term immuno-suppression and genetic syndromes e.g. xeroderma pigmentosum and albinism. Actinic keratoses are regarded by some authorities as premalignant lesions that may transform into invasive squamous cell carcinoma (SCC) and by others as in situ SCC that may progress to an invasive stage. The risk of malignant change appears low; up to 0.5% per lesion per year. Up to 20-30% of lesions may spontaneously regress but in the absence of any reliable prognostic clinical indicators regarding malignant potential active treatment is considered appropriate. Actinic keratosis lesions may present as discrete hyperkeratotic papules, cutaneous horns, or more subtle flat lesions on sun-exposed areas of skin. The single most helpful diagnostic sign is an irregularly roughened surface texture: a sandpaper-like feel almost always indicates actinic damage. Dermatoscopy can be helpful in excluding signs of basal cell carcinoma when actinic keratosis is non-keratotic. It is always important to consider the possibility of SCC. The principal indication for referral to secondary care is the possibility of cutaneous malignancy. However, widespread and severe actinic damage in patients who are immunosuppressed is also a reason for referral.

Improving detection of non-melanoma skin cancer Non-melanoma skin cancer.

Basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs) are clinically and pathologically distinct and both are locally invasive. However, while BCCs rarely metastasise, SCCs have the potential to do so especially when they arise on the ears or lips. UV radiation is the most important risk factor for non-melanoma skin cancer (NMSC). The tumours most commonly arise in fair-skinned individuals on sun-damaged skin, especially the face. Incidence rises with age. Patients with one NMSC have a higher risk of developing another NMSC and of malignant melanoma. SCCs are frequently more difficult to diagnose than BCCs. Well differentiated lesions have a pronounced keratotic element. Poorly differentiated SCCs tend to be pink or red papules or nodules, lacking keratin, which may ulcerate. Around 5% of SCCs metastasise. High-risk SCCs include those: on the ear, lip, or sites unexposed to the sun and in chronic ulcers, scars or Bowen's disease. SCCs > 20 mm in diameter or > 4 mm in depth are high risk. Patients who are immunosuppressed, have poorly differentiated tumours or recurrent disease are also at increased risk. Patients with a slowly evolving or persistent skin lesion where cancer is a possibility should be referred to a dermatologist. Lesions suspected of being BCC should be referred routinely. Urgent referral should be reserved for cases where there is concern that a delay may have a significant impact because of the size or site of the lesion. Any non-healing lesions >1 cm with marked induration on palpation, showing significant expansion over eight weeks, should be referred urgently as they may be SCCs.

Managing urticaria in primary care.

Urticaria is characterised by transient wheals that consist of a swollen palpable centre often surrounded by an erythematous flare, associated with itching or, less commonly, a burning sensation. Individual wheals usually disappear within 1 to 24 hours leaving normal skin. Wheals may be accompanied by angioedema, a more deep-seated flesh-coloured or erythematous swelling of skin or mucous membrane, which may last longer than 24 hours. Urticaria is classified as acute when it resolves within six weeks and chronic when its duration exceeds six weeks. Chronic urticaria is now sub-classified into chronic spontaneous urticaria (CSU) and chronic inducible urticaria. The prognosis for eventual recovery from spontaneous and inducible urticaria is excellent. However, the time course is unpredictable and may extend to years, often following a relapsing and remitting course. Urticaria results from the release of inflammatory mediators from dermal mast cells, resulting in vasodilatation, plasma extravasation, recruitment of immunologically active cells and sensory nerve stimulation. The cause of urticaria cannot usually be precisely identified for most affected individuals. IgE-mediated food allergy is rarely the cause of CSU in patients with the daily appearance of urticarial lesions, although it should be considered in CSU patients with intermittent symptoms. For patients with CSU a differential full blood count and inflammatory markers are all that are routinely recommended. It is also reasonable to test thyroid function and check for circulating thyroid autoantibodies as there is an association between CSU and thyroid autoimmunity.

Diagnosis directs treatment in fungal infections of the skin.

Dermatophyte fungi are confined to the keratin layer of the epidermis and include three genera: Microsporum, Epidermophyton and Trichophyton. These infections can be transmitted by human contact (anthropophilic), from the soil (geophilic) and by animal (zoophilic) spread. Dermatophyte infections usually present as an erythematous, scaly eruption, which may or may not be itchy. Asymmetry is an important clinical clue to fungal infection, as is annular morphology. Examination under ultraviolet (Wood's light) can be helpful. The gold standard for diagnosing cutaneous fungal infections is microscopy and culture of scale, hair or nail, and a definite diagnosis is desirable before commencing treatment, especially with oral therapy. Any dermatophyte species affecting the body can affect the hands. The most common organism is T. rubrum. Tinea corporis infection affects the trunk mainly in children and adolescents, and all genera of dermatophyte can cause it. Tinea cruris infection involves the groin region and is more common in men than women. T. rubrum is the most common causative dermatophyte. The clinical features of tinea capitis include patchy hair loss with varying degrees of scale, erythema and pustules. Infected hairs tend to break at the base, leaving stubble. Occasionally, there is invasion of the visible epidermis, resulting in a boggy, painful swelling with associated alopecia and regional lymphadenopathy known as a kerion.

Improving the management of seborrhoeic dermatitis.

Seborrhoeic dermatitis usually starts at puberty with a peak incidence at 40 years of age and is more common in males. Patients develop symmetrical, well demarcated, dull or yellowish red patches and plaques with overlying adherent, yellowish greasy scales. Seborrhoeic dermatitis has a distinctive distribution in areas rich in sebaceous glands - the scalp, eyebrows, glabella, nasolabial and nasofacial folds, cheeks, peri-auricular skin, pre-sternal and interscapular areas. It may occur in flexures, especially the axillae, groin, anogenital skin, infra-mammary skin and the umbilicus. Some patients may develop blepharitis with erythematous eyelids and destruction of eyelash follicles. Patients with HIV infection, neurological diseases, including parkinsonism and cranial nerve palsies, have a higher incidence of seborrhoeic dermatitis. Patients presenting with sudden onset severe seborrhoeic dermatitis should be screened for risk factors for HIV. Patients should be referred in the following situations: diagnostic uncertainty - consider other differential diagnoses; failure to respond to first-line treatment after four weeks - consider secondary changes e.g. bacterial infection, flexural intertrigo, lichenification, otitis externa; and severe/widespread disease. Patients with seborrhoeic dermatitis have a good prognosis, particularly infantile seborrhoeic dermatitis, which usually remits within a few weeks or months and does not recur.

Improving the management of rosacea in primary care.

Rosacea is more common in women than men and occurs more frequently in fair-skinned individuals, usually in the middle years of life. It tends to localise to the cheeks, forehead, chin and nose, sometimes showing marked asymmetry. Only very occasionally does it involve areas other than the face. Rosacea is usually characterised by erythematous papules, pustules, and occasionally plaques (papulopustular rosacea), which fluctuate in severity, typically on a background of erythema and telangiectasia. In some individuals, facial redness can be prominent and permanent (erythematotelangiectatic rosacea). Important distinguishing features from acne are a lack of comedones, absence of involvement of extra-facial areas, and the presence of flushing. Hypertrophy of facial sebaceous glands, sometimes with fibrotic changes, may result in unsightly thickening of the skin. Men, in particular, may develop marked enlargement and distortion of the nose. Occasionally, the predominant feature of rosacea is swelling of the eyelids and firm oedematous changes elsewhere on the face. Involvement of the eyes is an important, underdiagnosed complication that may result in significant ocular morbidity. Involvement of the external eye surfaces by rosacea usually necessitates ophthalmological advice. There is often no correlation between the degree of ocular and cutaneous rosacea, and ocular rosacea may occur alone. Rosacea is a disfiguring condition that can have a major psychosocial impact, and its detrimental effect on emotional health and quality of life is often overlooked.

Intense nocturnal itching should raise suspicion of scabies.

Scabies is caused by infestation with a parasitic mite Sarcoptes scabiei var hominis. The itch and rash appear to be largely the result of a delayed (type IV) allergic reaction to the mite, its eggs and excreta. Scabies is spread by a mite transferring to the skin surface of an unaffected person, usually by skin to skin contact with an infested person, but occasionally via contaminated bed linen, clothes or towels. In crusted scabies, mites are also dispersed within shed scales, enabling the condition to be contracted from contaminated surfaces. Patients with classical scabies usually present with an itchy non-specific rash. Often, the history alone can be 0032-6518 virtually diagnostic. An intense itch, affecting all body regions except the head, typically worse at night, appearing to be out of proportion to the physical evidence, with a close contact also itching, should prompt serious consideration of scabies. The generalised hypersensitivity rash consists of erythematous macules and papules with excoriation. Close inspection will reveal burrows usually up to 1 cm in length. The pathognomic sign of scabies is the presence of burrows. The crusted variant of scabies may not be itchy. It is characterised by areas of dry, scaly, hyperkeratotic and crusted skin, particularly on the extremities. Referral to secondary care should be considered in the following cases: diagnostic doubt; patient under two months of age; lack of response to two ourses of different insecticides; crusted scabies; or history suggests a isk of sexually transmitted infection. Outbreaks of scabies in institutions should be referred to the local health protection services.

Improving outcomes in patients with psoriasis.

Psoriasis is a heterogeneous inflammatory disorder that targets the skin and joints. It affects 1.3-2% of the population. The diagnosis of plaque psoriasis is usually straightforward, a helpful diagnostic clue is the tendency for silver scales to appear after gentle scratching of a lesion. Stress, streptococcal infection and drugs including beta-blockers, antimalarials and lithium may precipitate or exacerbate psoriasis. Psoriasis, especially when severe, predisposes to metabolic syndrome, and patients with psoriasis are at increased risk of ischaemic heart disease, hypertension, stroke, type 2 diabetes and hyperlipidaemia. Additionally, psoriasis sufferers appear at increased risk of uveitis, inflammatory boweldisease, lymphoma, non-melanoma skin cancer, COPD and venous thromboembolism. Psoriasis should be assessed on the basis of: severity, impact on physical, psychological and social wellbeing, symptoms of arthritis and the presence of comorbidities. Poor response to topical therapy may be as much to do with lack of compliance as with lack of efficacy. The number of treatments each day should be kept to a minimum, and patients should be reviewed after four weeks when initiating or changing topical therapy to improve adherence to treatment and assess response. The majority of patients with psoriasis can be managed in primary care, although specialist care may be necessary at some point in up to 60% of cases. Patients with erythrodermic or generalised pustular psoriasis should be referred for a same day dermatological opinion, and if psoriatic arthritis is suspected, early referral for a rheumatological opinion is recommended.

Alopecia areata: more than skin deep.

Alopecia areata is a chronic inflammatory non-scarring condition affecting the hair follicle that leads to hair loss ranging from small well defined patches to complete loss of all body hair. In about 80% of affected individuals there is spontaneous regrowth within a year. It can present at any age, although 60% of patients develop their first episode of hair loss before the age of 20. There is a family history of alopecia areata in 20% of cases indicative of a genetic basis. A positive family history is prognostic of troublesome alopecia areata, as are onset in childhood, ophiasis (involvement of the scalp hair margins), nail changes and concurrent atopic disease. However, the severity of hair loss at presentation appears to be the strongest predictor of long-term outcome. There is an association with autoimmune diseases, including vitiligo, diabetes, pernicious anaemia and thyroid disease, suggesting that alopecia areata itself is an autoimmune disease, although this is still unproven. Alopecia areata normally presents with hair loss in discrete, well circumscribed patches, which may be small (<1 cm) to very large. Close examination of the periphery of a lesion with a magnifying glass will often reveal short hairs which taper in diameter from their tip to the point at which they emerge from the skin. These 'exclamation mark' hairs are diagnostic of alopecia areata. Individuals with alopecia areata should be referred for dermatological advice if there is diagnostic uncertainty, they have extensive hair loss, they are suffering severe psychological distress or they would like a wig.

Be vigilant for scurvy in high-risk groups.

Scurvy is caused by prolonged dietary deficiency of vitamin C, the plasma concentration of which appears inversely related to mortality from all causes. Its clinical importance relates principally to its role as a cofactor in a number of enzyme reactions involved in collagen synthesis, dysfunction of which disrupts connective tissue integrity, resulting in impaired wound healing and capillary bleeding. In the UK, overt scurvy is diagnosed only rarely. However, subclinical vitamin C deficiency appears quite common, one study estimated that 25% of men and 16% of women in the low income/materially deprived population had vitamin C deficiency, with smoking a strong predictor. Because many of the early symptoms of vitamin C deficiency (fatigue, malaise, depression and irritability) are non-specific, the diagnostic possibility of scurvy is usually delayed until haemorrhagic manifestations occur. The classical cutaneous features consist of perifollicular purpura, contorted (corkscrew) hairs and follicular hyperkeratosis, particularly affecting the legs. Large areas of purpura or ecchymosis may occur. Swelling and bleeding of the gums is an early mucosal symptom, and progressively severe gum disease causes loss of teeth. Subperiosteal haemorrhage, particularly in the femur and tibia, can present as pain, pseudoparalysis, swelling and discoloration of the legs. Haemorrhage into joints and muscle is very uncomfortable. Diagnosis is generally made on the basis of clinical features, corroborated by a history of dietary inadequacy, and the subsequent rapid resolution of symptoms with the restoration of an adequate vitamin C intake.

Prompt treatment of acne improves quality of life.

Acne vulgaris is an inflammatory disorder of the pilosebaceous (hair follicle) units. It may be exacerbated by stress, topical greasy preparations that encourage blockage of the pores, trauma and humid climates. Certain medications may induce or exacerbate acne, including some oral and implanted contraceptives, and anabolic steroids. Occasionally, 'normal' acne can dramatically deteriorate: this may be due to a Gram-negative folliculitis superimposed on acne being treated with long-term antibiotics, or the development of one of the much more severe, destructive and aggressively scarring forms. Disfigurement from inflammation, pigmentation changes and scarring often causes embarrassment, and not infrequently undermines confidence and lowers self-esteem. Acne can also potentially induce much more serious psychological distress. It may take up to four to six months before the full benefit of treatment is apparent. Patients should be referred to a dermatologist if they: have a very severe variant; severe social or psychological problems; are at risk of scarring; have failed to respond to treatment or are suspected of having an underlying endocrinological cause.

Improving the management of atopic eczema in primary care.

Although generally considered a childhood ailment, 38% of patients in the UK with atopic eczema are adults. The diagnosis of uncomplicated atopic eczema is based on clinical history and visual assessment. Atopic eczema may be complicated by secondary infection, particularly staphylococcal and streptococcal, and herpes simplex virus may cause eczema herpeticum, which is uncomfortable and potentially dangerous. Patients or carers should receive a full explanation of how to use topical treatments and a demonstration of how to apply dressings, if applicable. Emollients are the mainstay of treatment. They should be applied liberally and frequently and their use continued during periods of treatment with corticosteroids. Topical calcineurin inhibitors should be considered, in patients two years and older, for the acute treatment of moderate and severe atopic eczema that has not been controlled by topical corticosteroids or if there is a serious risk of adverse effects from further corticosteroid use. Short-term use of oral antibiotics in infected eczema is recommended.

Epidermolysis bullosa simplex in Scotland caused by a spectrum of keratin mutations.

Epidermolysis bullosa simplex (EBS) is an inherited skin disorder caused by mutations in keratins K5 (keratin 5) and K14 (keratin 14), with fragility of basal keratinocytes leading to epidermal cytolysis and blistering. Patients present with widely varying severity and are classified in three main subtypes: EBS Weber-Cockayne (EBS-WC), EBS Köbner (EBS-K), and EBS Dowling-Meara (EBS-DM), based on distribution and pattern of blisters. We could identify K5/K14 mutations in 20 out of the 43 families registered as affected by dominant EBS in Scotland; with previous studies this covers 70% of all Scottish EBS patients, making this the most comprehensively analyzed EBS population. Nine mutations are novel. All mutations lie within five previously identified rod domain hotspots and the severest blistering was associated with mutations in the helix boundary motifs. In some cases, the same mutation caused symptoms of EBS-WC and/or EBS-K, both within and between families, suggesting a contribution of additional factors to the phenotype. In some patients, no mutations were found in K5, K14, or K15, suggesting involvement of other genes. The results confirm that EBS is best considered as a single disorder with a spectrum of phenotypic variations, from severe EBS-DM at one extreme to mild EBS-WC at the other.