Flexural dermatoses

F A Campbell, A Drummond, D T Roberts

HK Pract 2003;25:427-434

Summary

Many common dermatological conditions affect the skin folds, with or without involvement elsewhere. Diagnostic difficulties arise when the distribution of the rash is exclusively flexural, or when superimposed maceration and infection are also present. When treating flexural rashes it is important to keep the area dry and address issues of incontinence, excess sweating and obesity. Secondary infection with bacteria and fungi should be screened for and appropriately treated. In general, potent or super potent topical steroids should not be applied to these areas unless on the advice of a dermatologist.

摘要

許多常見的皮膚疾病影響皮膚皺襞，有些可以影響其他部份。如果皮疹只獨特地分佈在曲位， 或加上浸漬和感染的時候，便會增加診斷的困難。治療曲位皮疹時，重要的是保持乾爽和留意有無失禁， 汗水分泌過量和肥胖。繼發性的細菌和真菌感染，要及時調查和適當治療。除非得到皮膚專科醫生的建議， 否則不應在患處局部塗抹強力或超強力的類固醇藥物。

Introduction

Common dermatological conditions affecting the skin folds are many and diagnosis may present difficulties. They may be grouped under a common heading as flexural dermatoses and may be primary or secondary to diabetes, obesity, excessive sweating or poor hygiene. Care must be taken to address the primary problem when managing these conditions. Many cases can be successfully managed by the family physician/general practitioner and recalcitrant cases should be referred for specialist opinions.

Atopic eczema

This is a common condition to diagnose and manage in general practice. After the infantile phase (up to 18 months) the typical sites affected are the elbow and knee flexures (Figure 1). The hands, wrists and ankles are other commonly affected areas, although any part of the body may be involved. The clinical features include erythema, papules, vesicles and scaling. Lichenification can occur in more chronic disease. It is classically itchy, leading to excoriations. It often becomes secondarily infected with Staphylococcus aureus resulting in erosions and crusting. The diagnosis is rarely difficult but scabetic infestation should always be considered and examined for carefully.

Figure 1: Atopic eczema affecting the popliteal fossa showing erythema, scaling and excoriations

Figure 2: Extensive seborrhoeic dermatitis of infancy

Seborrhoeic dermatitis

Seborrhoeic dermatitis is a chronic scaling inflammatory condition affecting areas rich in sebaceous glands. The commonest sites are the face and upper trunk but it also occurs in skin flexures where it causes sharply demarcated erythema and greasy scaling. Crusting and fissuring are complicated by sweating and infection which in turn leads to weeping and extension beyond the body folds (Figure 2). Chronic cases relapse and remit. They may be modified by contact allergy or by secondary infection with organisms such as Candida albicans. The highest incidence is in 18-40 years old. Males are more commonly affected than females. In HIV positive patients exacerbation of seborrhoeic dermatitis may indicate progression of HIV infection.¹ In later life seborrhoeic dermatitis may complicate Parkinson's Disease. Differential diagnoses should include psoriasis, contact dermatitis and fungal infection. Most cases respond to a topical imidazole combined with a mild to moderately potent topical steroid.

Contact dermatitis

Axillary contact dermatitis is more commonly caused by irritation rather than allergy. Allergy may be due to fragrances, textiles or antiperspirants and the rash is often worsened by the occlusive effect of clothing.

In the groin contact dermatitis may be due to antiseptics, medicaments and fragrances. Contraceptive devices and spermicidal creams may also cause irritation.

Sensitisers in the perianal area include prescribed topical medicaments as well as over-the-counter preparations such as haemorrhoid creams. A thorough clinical history is essential to identify any potential irritants or allergens.

Psoriasis

Psoriasis is a non-infectious inflammatory dermatosis which can occur at any age and which may be localised or widespread. Classic psoriasis presents as scaly red plaques overlying the elbows and knees but several other clinical patterns are recognised.

Flexural psoriasis specifically affects the axillae, sub-mammary area, natal cleft, groin and vulva as well as the umbilicus and the retro-auricular folds. It may occur as a primary phenomenon or as a result of "Koebnerisation" of a pre-existing flexural dermatosis.

It is typically a disease of adulthood although some babies' "napkin psoriasis" (a psoriasiform eruption of the napkin area) may progress to true psoriasis when they are older. Typical silvery scaling is absent due to sweating and friction but lesions are usually well-demarcated and fissuring may be seen at the deepest aspect of the crease, especially in the natal cleft (Figure 3). The differential diagnosis includes candidiasis or seborrhoeic dermatitis. Flexural psoriasis will normally respond to medium-potency topical steroids either alone or in combination with an antifungal/antibacterial agent but they should be used sparingly to minimise the potential risk of striae formation.

Figure 3: Flexural psoriasis of the groin area associated with typical chronic plaque psoriasis

Figure 4: Hidradenitis suppurativa affecting the axilla with resultant scarring

Hidradenitis suppurativa

This is a chronic, relapsing inflammatory disease characterised by abscesses, fistulas and scarring (Figure 4). It is due to a defect in follicular epithelium rather than the apocrine gland as previously thought. The main sites affected are the axillae, groin and perineum, but the sub-mammary folds, genitalia, buttocks, nape of the neck and even the scalp can be affected. The female/male ratio is 2.5:1 with the prevalence being estimated at between 1:100 and 1:600. A positive family history is not unusual and in reported cases an autosomal dominant inheritance pattern is seen.² This disorder does not occur before puberty nor start after the menopause. Many patients often delay presentation to their family physician/general practitioner for psychosocial reasons, especially when the groins are affected.

Aetiological factors such as hyperandrogenism, obesity, smoking, diabetes and chemical irritants are not consistently associated with the condition. Hidradenitis suppurativa is common and easily diagnosed in most cases once the family physician/general practitioner is aware of the disorder. The differential diagnosis includes furuncles, carbuncles, vegetating pyoderma, lymphogranuloma inguinale and Crohn's disease. Treatment usually consists of medical therapy in the early stages. Antibiotics tend to be of limited benefit but can reduce discharge and odour, and reduce pain. In more advanced disease there is no evidence that treatment other than surgery has any effect on the natural history of the condition, which rarely spontaneously resolves.

Intertrigo

Intertrigo is a term that simply means an inflammatory dermatosis of any flexural site, particularly the sub-mammary or genitocrural folds (Figure 5). However, it is generally used to describe infected flexural skin. Predisposing factors include obesity, excess sweating, poor hygiene, urinary or faecal incontinence, diabetes mellitus, old age and infancy. The usual bacterial organisms involved are Staphylococcus aureus, Escherichia coli and Proteus mirabilis with haemolytic streptococci being less common. Clinically the skin is erythematous, eczematous and moist. Papules and pustules rupture and result in painful erosions and fissures. Fungal intertrigo is generally due to Candida albicans and is especially prevalent in infants, diabetics and the obese. It has a scaling irregular edge, and satellite papules and pustules, that help to differentiate it from bacterial infection. The differential diagnosis includes tinea cruris, seborrhoeic dermatitis, flexural psoriasis, Hailey-Hailey disease and Darier's disease.

Figure 5: Intertrigo affecting the submammary area and axillae in an obese, elderly female

Figure 6: Tinea cruris showing a well demarcated erythematous rash with scaly edge

Fungal

Fungal infections of the flexures are generally caused by either dermatophytes or yeasts. Dermatophyte infections affect the stratum corneum, the nails and the hair and are subdivided into the genera Trichophyton, Epidermophyton and Microsporum. Clinical features depend on the site of involvement. Tinea cruris is usually caused by Trichophyton rubrum and is commoner in males (Figure 6). It usually results from auto-infection from the toe clefts but care should be taken to avoid the sharing of sports towels and clothing which may also promote transmission of infection. Groins and sometimes thighs and scrotum are affected. Positive skin scrapings from the scaly lesional edge will confirm the diagnosis. Treatment should include attempts to reduce friction and sweating along with the application of topical anti-fungal agents.

Candida albicans is a yeast found as a commensal in the gastrointestinal tract. It can lead to opportunistic infection in flexural areas especially in the presence of diabetes, obesity, excessive sweating and poor hygiene. It is commoner in females and affected sites become red and moist with exudate spreading beyond the body folds. The irregular edge is less well-defined than in dermatophyte infection and tiny subcorneal pustules may be a feature. The use of topical steroids for the intense itch may modify the appearance but swabs should help to confirm the diagnosis. Routine management is similar to that of tinea cruris and includes careful washing and drying of the area in conjunction with the application of an anti-fungal cream. Moist macerated areas benefit from potassium permanganate soaks and good glycaemic control will help symptom relief in diabetics.

Viral

Viral infections are less common in the flexures than in some other sites but genital herpes is known to affect the vulva and perineum in females and the perianal area in homosexual males. The axillae are a common site for molluscum contagiosum infection especially in children living in temperate climates. Lesions are usually self-limiting and regress after a number of months. Human papilloma virus may cause warts in flexural areas and these should be distinguished from common skin tags.

Erythrasma

This is a mild, chronic, superficial skin infection caused by Corynebacterium minutissimum seen most commonly in adults (Figure 7a).³ The sites of predilection are the toe clefts, axillae, intergluteal and crural folds, and the submammary area. Patches are sharply marginated and irregularly shaped. New lesions are red and smooth but later turn brown and scaly. In temperate climates most lesions are asymptomatic, but in the tropics itch can be present. The differential diagnosis includes pityriasis versicolour, psoriasis, candidiasis and dermatophytosis. Investigations should include skin swabs for microscopy and culture, and skin scrapings for mycological examination to exclude concurrent infections. Wood's light examination will show coral pink fluorescence (Figure 7b). The treatment of choice is oral erythromycin but alternatives include topical fucidin, topical imidazole, topical or oral tetracycline.

Figure 7a: Erythrasma affecting the groin area. (Patient of Professor U Budimulja)

Figure 7b: Wood's light examination showing coral pink fluorescence of erythrasma (Patient of Professor U Budimulja)

Acute generalised exanthematous pustulosis (AGEP)

Drugs most often trigger this pustular eruption, although viral infections can also cause this condition.⁴ The interval between drug intake and the development of the rash may only be a few hours, especially with antibiotics, or as long as 2 - 3 weeks. The rash begins in the axillae and groin area and/or on the face. Oedematous erythema develops very rapidly on which dozens to hundreds of tiny, non-follicular, sterile pustules form. Mild oral involvement is seen in 20% of cases. High fever and a leucocytosis are present. The pustules resolve spontaneously within 15 days as long as the offending drug is stopped. The prognosis is good unless superimposed bacterial infection of the skin develops which can result in life-threatening septicaemia. AGEP may be difficult to differentiate from pustular psoriasis, subcorneal pustular dermatosis (Sneddon-Wilkinson), pustular vasculitis, drug hypersensitivity syndrome and toxic epidermal necrolysis. The cases that present to the general practitioner are usually referred urgently to a dermatologist for diagnosis and management.

Systemic contact dermatitis (Baboon syndrome)

This is a peculiar form of contact dermatitis that develops after systemic (ingestion, inhalation or injection) allergen exposure in a patient previously sensitised by cutaneous exposure. The most frequently incriminated allergens include mercury, ampicillin, amoxicillin, nickel, heparin and food additives.⁵ The exanthematous eruption involves the buttocks, anogenital area and the limb flexures. The rash will resolve spontaneously on avoidance of the allergen.

Acanthosis nigricans

Acanthosis nigricans is an uncommon disorder most marked in the flexural areas especially the axillae, groins and sides of neck. Affected skin becomes hyperpigmented and roughened and as the disease progresses the epidermal thickening produces a warty velvety surface (Figure 8). Acanthosis nigricans is subclassified into several groups depending on the aetiology but can be broadly divided into benign or malignant forms. The benign group includes rarer genetic, naevoid and drug-induced types but most cases are thought to be associated with insulin resistance and hyperinsulinaemia. Insulin binds to specific cell receptors and acts as a growth factor for keratinocytes and fibroblasts thus producing the classic skin changes. Patients should be screened for endocrine disease and appropriate intervention may lead to a reduction in the severity of the skin changes.

Malignant acanthosis nigricans is more severe, extensive and pigmented. Mucous membranes and mucocutaneous junctions may be affected especially round the lips and eyes. Involvement of the palmer skin may cause a rugous appearance known as tripe palm. Associated tumours are usually adenocarcinomas and skin lesion, which can precede tumour symptoms by several years may regress in those amenable to surgery.

Pseudoacanthosis nigricans is thought to be a benign reversible complication of obesity, more commonly seen in non-caucasians and probably also due to insulin resistance.⁶

Figure 8: Acanthosis nigricans affecting the axilla and neck

Figure 9: Brown, greasy papules affecting the axilla and chest in a patient with Darier's disease

Figure 10: Hailey-Hailey disease showing moist vegetations and fissures

Darier's disease (Keratosis follicularis)

Darier's disease is inherited as an autosomal dominant disorder which usually presents in children or young adults. Affected individuals develop firm greasy yellow-brown papules on the seborrhoeic areas of the trunk, scalp and face but there may also be flexural involvement especially in the anogenital region, groins and natal cleft (Figure 9). In these areas lesions are thickened and warty and may become malodorous as a result of secondary infection particularly with Staphylococcus aureus or Herpes simplex. Painful blisters and erosions may in turn complicate such infections. Acanthosis nigricans and Hailey-Hailey disease should be considered in the differential diagnosis but most patients with Darier's Disease will have typical lesions at other sites.

Treatment ranges from emollients, keratolytics, topical steroids and retinoids in mild to moderate cases at one end to oral retinoids in those with more severe disease at the other end. Systemic antibiotics and antiviral agents are useful for secondary infection.

Hailey-Hailey disease (Familial benign chronic pemphigus)

This is a rare, painful, intraepithelial blistering disease with patients usually in their twenties or thirties at presentation.⁷ It is an autosomal dominant condition with the gene mutation localised to chromosome 3q. The sites affected include the groin, axillae and sides of the neck. Clinical features include flaccid vesiculopustules, crusted erosions or expanding annular plaques with central healing. Affected sites are malodorous and may be hypertrophic with soft, moist vegetations and fissures (Figure 10). Herpes simplex infection causes painful exacerbations and is difficult to distinguish clinically from vesicular Hailey-Hailey disease. The differential diagnosis includes candidiasis, tinea infection, impetiginised eczema, pemphigus vegetans and Darier's disease. A skin biopsy with immunofluorescene will help to establish the correct diagnosis.

Fox-Fordyce disease

This is a rare disease of unknown aetiology which affects the apocrine glands in the axillae and to a lesser extent the anogenital region. It is commoner in females perhaps due to some hormonal effect, and soon after puberty affected individuals develop intense itch in association with flesh-coloured or slightly pigmented papular lesions. These are thought to be due to inflammatory changes in the sweat duct leading to plugging and subsequent sweat retention. Itching may be exacerbated by any stimulus which promotes apocrine secretion and the disease tends to run a protracted course lasting beyond the menopause. Some patients improve during pregnancy but relapse after delivery. Treatment options are limited but improvement occasionally has been noted with topical steroids, retinoids or UVB. In extreme cases surgical resection and more recently liposuction-assisted curettage has been beneficial.⁸

Bullous diseases

Pemphigus vulgaris is a rare potentially fatal autoimmune disease of the skin and mucous membranes. Affected patients are usually middle-aged to elderly and since early lesions often involve mucous membranes they may be wrongly diagnosed as aphthous ulcers, Herpes simplex stomatitis or bullous lichen planus. Skin involvement of the scalp, face and trunk usually follows and flexural areas may have hyperkeratotic vegetating and erosive lesions. A rare variant of pemphigus vulgaris is pemphigus vegetans which usually presents at a younger age and which localises to flexural areas.⁹ The differential diagnosis of the vegetating lesions should include Darier's disease and Hailey-Hailey disease but such cases should be referred to a dermatologist for further investigation and management.

Rarer still is Epidermolysis bullosa a bullous disorder which may be congenital or acquired and which in some forms may affect "inverse" or flexural areas producing blistering and subsequent scarring. The clinical spectrum of disease may vary from incidental to life-threatening and again should be investigated and managed in a specialist unit.

Lichen planus

This condition rarely affects children and 85% of cases will clear within 18 months. This intensely itchy rash is characterised by shiny, violaceous, polygonal, flat-topped papules. On the surface are white lines known as Wickham's striae. Many types of lichen planus have been described which vary in both distribution and morphology. The commonest sites affected include the distal volar surfaces of the limbs and mucous membranes. Peri-anal changes are well recognised with the axillae, inframammary region and groins being less commonly involved. Some patients have disease confined solely to these flexural sites.¹⁰ Referral to a dermatologist for assessment is required for these patients.

Langerhans' cell histiocytosis

This is a rare condition where Langerhans' cells accumulate in various tissues, including the skin, and cause tissue damage. Ulceration in the flexures and in the groin or perianally is a common presentation in adults. In both adults and children the condition can mimic seborrhoeic dermatitis. In infants it may be mistaken for napkin dermatitis. Examination of a skin biopsy with specific marker studies is usually required to make the diagnosis.

Key messages

1. Flexural dermatoses may be primary or secondary to diabetes, obesity, excessive sweating or poor hygiene.
2. Care must be taken to address the primary problem.
3. Many cases can be successfully managed using topical combination therapy, however, recalcitrant cases should be referred for a specialist opinion.