Tuesday, 17 July 2012


Leprosy (Gk lepros, scaly – Hansen’s disease, Hansen was a Norwegian bacteriologist/leprologist) is a chronic granulomatous disease (the granulomas can be linear following nerves) caused by Mycobacterium leprae (M. Leprae) principally affecting  peripheral nerves and the skin (the bacteria have a predilection for cool skin). The disease has been endemic in India and the Far East since ancient times. It is generally a tropical infection. 86% of leprosy patients reside in six countries (India, Brazil, Indonesia, Myanmar “Burma”, Madagascar and Nepal). However, leprosy has not always been a tropical disease; it was endemic in Norway until the early 20th century. Leprosy can be seen outside the tropics as people migrate to live in other countries. Leprosy tends to be over-diagnosed in endemic countries and under-diagnosed in non-endemic countries. In any population it is important for the physician to know the normal range of skin colour and texture, the common endemic skin diseases that may coexist with leprosy and the common medical and artefactual practices that may cause lesions resembling those of leprosy.

The term ‘mycobacterium’ has been given to a large group of bacteria producing mould-like pellicles when grown on liquid media. All are slender, non-motile, aerobic, rods with a waxy coating that makes them resistant to most stains. Once stained, however, they are not easily decolourized (acid-fast). M. leprae has never been grown in vitro. Growth has been achieved in e.g. the nine-banded armadillo. This animal has provided mycobacteria for genetic and biochemical analysis and the production of trial vaccines. Recent work based on amino acid sequencing of M. leprae proteins suggests that there are subtle strain differences. The organism synthesizes a species-specific lipid, phenolic glycolipid (PGL).  The highly conserved Toll-like receptors on the surface of monocytes and macrophages recognize mycobacterial lipoproteins.   PGL-1 antibodies can be detected and seropositivity correlates with bacterial load measured by slit-skin smears. The assertion that  M. lepromatosis is a new leprosy-causing species is not proven.

Leprosy is a chronic disease with a long incubation period (many years).  Nasal discharges from untreated lepromatous leprosy patients, who are often undiagnosed for several years, are the main source of infection in the community. Infection probably occurs through the nose thus M. Leprae is inhaled, multiplies on the inferior turbinates and has a brief bacteraemic phase before binding to Schwann cells and macrophages. Accordingly, the nose seems to be both the portal of exit and the portal of entry.  The skin is unimportant in leprosy transmission. Subclinical infection with M. leprae is probably common and there is no reliable test for determining whether a person has encountered M. leprae and mounted a protective immune response. Self-healing often occurs in early monomacular tuberculoid cases.

Lepromatous leprosy represents a failure of cell-mediated immunity (CMI) specifically towards M. leprae with resultant bacillary multiplication, spread and accumulation of antigen in infected tissues. The absence of activated lymphocytes and macrophages means that nerve damage is slow and gradual in onset. In tuberculoid leprosy, CMI is strongly expressed, so that the infection is restricted to one or a few skin sites and peripheral nerves. Lymphocytic infiltration rapidly causes nerve damage. Between those two polar forms lie the borderline forms of disease, with the extent of disease reflecting the balance between CMI and bacillary load. Borderline patients (borderline tuberculoid, BT; borderline, BB; borderline lepromatous, BL) are immunologically unstable.

There are important determinants of leprosy risk e.g. genetic factors and BCG vaccination. There is substantial cross-reactivity between BCG and M. leprae. The variable protection induced by BCG is due to early contact with environmental mycobacteria priming the immune system and conferring protective immunity against M. leprae. Being HIV positive does not appear to confer increased susceptibility to leprosy. Patients with concomitant infections have the usual granuloma formation even with low circulating CD4 counts. Co-infected patients appear to be at increased risk of developing leprosy reactions and the borderline types of leprosy dominate the clinical picture. Leprosy may also present as an IRIS phenomenon in HIV-positive patients who have recently started ART.

In tuberculoid leprosy only nerves and skin show clinical evidence of disease; lesions are few, often solitary. The condition may be purely neural, with pain and swelling of the affected nerve followed by anaesthesia and/or muscle weakness and wasting. Alternatively, a skin lesion appears with or without evidence of nerve involvement. The typical lesion is a plaque that is conspicuous, erythematous, copper coloured or purple, with raised and clear-cut edges sloping towards a flattened and hypopigmented centre.  Dark skins may not show the erythema. The surface is dry, hairless and insensitive, and sometimes scaly. A thickened sensory nerve may be palpated or a thickened nerve trunk may be felt in the vicinity.  Less commonly the lesion is a macule, erythematous in light skins and hypopigmented in dark skins. Such macules have a dry, hairless and insensitive surface. In tuberculoid leprosy, the granulomas collect in foci surrounding neurovascular elements. The granuloma invades the papillary zone and may even erode the epidermis, but acid-fast bacilli (AFB) are not usually seen. In tuberculoid leprosy, bacillary multiplication is restricted to a few sites and bacilli are not easily found (paucibacillary type of leprosy).

Lepromatous leprosy represents a failure of cell-mediated immunity specifically towards M. leprae with resultant bacillary multiplication, spread and accumulation of antigen in infected tissues (multibacillary type of leprosy). The absence of activated lymphocytes and macrophages means that nerve damage is slow and gradual in onset. In lepromatous  leprosy, haematogenous spread of bacilli occurs to cool, superficial sites, including eyes, upper respiratory mucosa, testes, small muscles and bones of hands, feet and face, as well as peripheral nerves and skin (e.g. nose and ears). The first clinical manifestations of lepromatous leprosy are usually cutaneous because nerve damage is slow and gradual in onset, but even these cutaneous manifestations may go unnoticed by the patient, who often complains of other early symptoms; these include nasal stuffiness, discharge and epistaxis, and oedema of legs and ankles due to increased capillary stasis and permeability. Cutaneous signs comprise macules, papules, infiltration or nodules, or all four. Macules are small, multiple, erythematous or faintly hypopigmented. Nodules usually have normal skin colour but sometimes are erythematous. If the patient remains untreated the lines of the forehead become deeper as the skin thickens. The thickened skin, most marked over the forehead and other areas of the face, starts to develop folds (thrown into folds) which hang down in conjunction with nodules (producing leonine facies). By this time anaesthesia is extensive and is accompanied by anhydrosis. Excessive compensatory sweating from unaffected areas, especially the axillae, becomes obvious. Moreover, there is loss (or thinning) of eyebrows and eyelashes (madarosis), the nose may collapse due to septal perforation and loss of the anterior nasal spine, the voice becomes hoarse and the upper incisor teeth loosen or fall out.  A slow fibrosis of peripheral nerves results in nerve thickening and bilateral ‘glove and stocking’ anaesthesia but sensation of palms and soles is retained until late in the disease (it generally spares warm skin such as palms and soles and midline of the back). Testicular atrophy leads to infertility, erectile dysfunction and gynaecomastia.  Dermatofibroma-like (histoid)lesions are distinctive round, regular, cutaneous nodules that stand out on normal skin. They are characteristic of lepromatous leprosy relapse after treatment but they can be the presenting lesions. In lepromatous leprosy, there is thinning of epidermis and flattening of rete ridges between dermal papillae and the papillary layer of the dermis appears as a clear band (grenz zone), whilst deeper in the dermis lies the typical diffuse leproma consisting of foamy macrophages, with the addition of a few lymphocytes and plasma cells. The dermis contains enormous numbers of AFB, singly or in clumps (globi). With treatment, the leproma shows increased foamy change, vacuolates and breaks up into discrete foci with fibrocytes at the periphery. These foci shrink as treatment is continued and bacilli become fragmented and granular.  Despite the large numbers of organisms in the nerve there is only a small inflammatory response; ultimately the nerve fibroses and is hyalinised.

In borderline leprosy, skin lesions are intermediate in number between those of the two polar types already described, depending on the position of the patient on the borderline spectrum, and are distributed asymmetrically. They may take the form of macules, plaques, annular lesions or bizarre-shaped bands. Plaques with a ‘punched-out’ appearance are characteristic of the middle of the spectrum. Damage to structures other than skin and nerves will not be manifest clinically in borderline leprosy, even though bacilli may be present in other tissue. Borderline leprosy is the commonest type of disease encountered and is unstable and ‘down-grades’ towards lepromatous, especially if untreated, or ‘upgrades’ towards tuberculoid. The formation of small granulomas is characteristic of borderline leprosy. Left untreated, borderline patients will downgrade towards the lepromatous end of the spectrum

The transitory stage of leprosy called indeterminate leprosy occurs in those whose immunological state has not yet been determined, and histopathologically there is a scattered non-specific histiocytic and lymphocytic infiltration with some concentration around skin appendages. Rarely, a single bacillus will be found within a dermal nerve. The indeterminate phase may last for months or years before resolving or giving way to one of the determinate types of leprosy. The classic skin lesion in indeterminate leprosy is most commonly found on the face, extensor surface of the limbs, buttocks or trunk. Indeterminate lesions consist of one or more slightly hypopigmented or erythematous macules, a few centimetres in diameter, with poorly defined margins.

Pure neuritic leprosy presents with asymmetrical involvement of peripheral nerve trunks and no visible skin lesions; on histopathology of a cutaneous nerve biopsy, all types of leprosy are seen. It is seen most frequently, but not exclusively, in India and Nepal where it accounts for 5–10% of patients.

Type 1 lepra reaction is a cellular hypersensitivity and the change in cellular immunity of the patient may be in either direction. The term reversal is used for an increase in cellular immunity and a shift towards the tuberculoid pole. The term downgrading is used for a loss of cellular immunity and a shift towards the lepromatous pole. Type 1 lepra reactions occur in borderline disease and are characterized by acute neuritis and/or acutely inflamed skin lesions (inflammation starts within some of the existing skin lesions but new lesions can appear). Despite the fundamental difference between reversal and downgrading reactions, they are clinically indistinguishable without careful history (downgrading reactions occur before therapy or if the therapy is inadequate and reversal reactions occur in response to adequate therapy*). It has been said that the patient undergoing reversal reaction (towards healing) does so “at the expense of his nerves”. In type 1 reaction, the changed skin lesions are not usually painful but the nerves can be EXTREMELY painful. In downgrading reactions, as cellular hypersensitivity is suppressed, type 2 reactions may TAKE OVER and the clinical picture becomes complicated. Type I reactions show an increase in lymphocytes and sometimes giant cells, as well as the formation of small clusters of epithelioid cells. This is the picture seen in the usual upgrading reaction. In downgrading reactions there is replacement of lymphocytes and epithelioid cells by collections of macrophages, and there is a corresponding increase in the number of bacilli.

Type 2 lepra reaction is a humoral hypersensitivity and is not associated with a shift along the spectrum. It is due to Ag-Ab reaction with the formation of immune complexes and gives rise to erythema nodosum leprosum [ENL] (commonest on the face and extensor surfaces of the limbs). ENL occurs in patients with multibacillary disease (borderline lepromatous leprosy and lepromatous leprosy). ENL may occur spontaneously or whilst on treatment and actually up to 50% of lepromatous leprosy patients may experience ENL. ENL manifests most commonly as painful red nodules on the face and extensor surfaces of limbs. Lesions last for a few days and are succeeded by crops of new ones. In contrast to type 1 reaction, the actual leprosy lesions appear unchanged clinically and the new lesions are commonest on the face and extensor surfaces of the limbs, but may also be seen elsewhere. Attacks are often acute at first, but may be prolonged or recurrent over several years and eventually quiet but insidious! The lesions may be superficial or deep, with suppuration ulceration or brawny induration when chronic. ENL is a systemic disorder, producing fever and malaise. It may be accompanied by uveitis, dactylitis, arthritis, neuritis, lymphadenitis, myositis and orchitis. In terms of nerve damage, ENL is usually less serious than type 1 reactions but it is often more prolonged.   ENL shows a mixed dermal infiltrate of neutrophils and lymphocytes superimposed on collections of macrophages. There are relatively more T lymphocytes of helper-inducer type (CD4+) than in non-reactive lepromatous leprosy. This appears to be due to an absolute reduction in the number of T-suppressor (CD8+) cells, which predominate in lepromatous leprosy. Histopathologically, the signature cell of ENL is the neutrophil. A vasculitis is often present.

Type 3 lepra reaction or the Lucio reaction/phenomenon (erythema necroticans) only occurs in patients with Lucio leprosy, a variety of lepromatous leprosy “diffuse lepromatous leprosy” [the skin of the whole body becomes diffusely thickened, rendering it stiff and smooth as in scleroderma and it is the purest form of lepromatous leprosy]. It is due to infarction consequent upon deep cutaneous vasculitis centred upon M. Leprae in vascular endothelial cells, and causing the appearance of irregularly shaped erythematous patches which become dark and heal, or form bullae and necrose, leaving deep painful ulcers that are slow to heal (large polygonal sloughing ulcerations, usually on the legs). The systemic upset is severe and can be fatal. In Lucio’s phenomenon the endothelial cells and macrophages in the dermis, contain numerous bacilli. There is usually only a mild inflammatory infiltrate, with fewer neutrophils than in ENL.

The posterior tibial nerve is the most frequently affected nerve. Posterior tibial nerve damage is serious because it causes paralysis and contracture of the small muscles of the foot and anaesthesia of the sole.

Blindness due to leprosy is a devastating complication, especially for a patient with anaesthetic hands and feet. Eye damage results from both nerve damage and bacillary invasion.

The term ainhum (Yoruba Nigerian, ‘to saw’) is applied to a specific type in which a painful constriction of the fifth toe occurs in adults, with eventual spontaneous amputation. Pseudoainhum is the term applied to other constricting bands which are congenital or secondary to another disease. Leprosy is a cause of pseudoainhum.

Leprosy is rarely a primary cause of death, but patients have a standardized death rate at least twice that of the general population due to the indirect secondary effects of the disease.

The diagnosis of leprosy is usually made clinically on the basis of two out of three cardinal signs, or by the demonstration of AFB in slit-skin smears (fluid and pulp from the dermis, collected on one side of the blade, are gently smeared on to a glass slide. The smear is then fixed over a flame and stained. A bloody smear is useless), or by histopathology typical of leprosy. The cardinal signs are: 1) anaesthesia of a skin lesion or in the distribution of a peripheral nerve, or over dorsal surfaces of hands and feet 2) thickened nerves, especially at the sites of predilection 3) typical skin lesions. The AFB load of a patient is determined by modified Ziehl–Neelsen staining of slit-skin smears. When performing a skin biopsy, the incision should be made down to subcutaneous fat, so that the whole depth of the dermis is included, otherwise leprous changes in the deeper layers of the dermis will be missed. PCR probes have been developed for the detection of M. leprae DNA in tissues from leprosy patients and it is possible, using a PCR–single strand polymorphism technique, to identify rifampicin-resistant isolates within hours. The use of PGL-1 antibody testing may be useful in assessing paucibacillary patients who are smear negative. Note that lepromatous patients produce a range of autoantibodies, both organ-specific (directed against e.g. nerve and testis), and non-specific, such as cardiolipin.

The AFB load of a patient is determined by modified Ziehl-Neelsen staining of slit-skin smears. Suspect lesions, and sites commonly affected in lepromatous leprosy, should be sampled (forehead, earlobes, chin, extensor surface of the forearm, buttocks and trunk). The density of bacilli is expressed using a logarithmic scale, extending from very few AFB to many per high-power field. A mean score, the bacterial index (BI), is derived by adding the scores from each site and dividing by the number of sites sampled. In untreated lepromatous leprosy, the BI is 5. or 6. The BI falls to zero in TT disease. With treatment, bacilli disappear from BB lesions in a few months and from BL lesions in a year or two. It may take 6–10 years for the last bacillary remnants to disappear from the skin in LL.

Lepromin test: A crude, semi-standardized preparation of heat killed bacilli from a lepromatous nodule or infected armadillo liver is used by intra-dermal injection. The lepromin test is a non-specific test of occasional value in classifying a case of leprosy. It is strongly positive in TT, weakly positive in BT, negative in BB, BL and LL, and unpredictable in indeterminate leprosy. It is not diagnostic, since it can be positive in people with no evidence of leprosy.

Differential diagnosis of leprosy depends on the type of lesion (e.g. in macular lesions: diseases such as vitiligo, pityriasis alba, and pityriasis versicolor – in plaques and annular lesions: diseases such as tinea corporis, sarcoidosis and cutaneous tuberculosis – in nodules:  diseases such as cutaneous leishmaniasis – in neural lesions: diseases such as diabetes and HIV infection). Mycosis fungoides should also be considered (as shown in the following photos).

The tumour cells in mycosis fungoides are CD4+ but CD8+ rather than CD4+ can be found and this is more common in this hypopigmented variant.  Histologically, these lesions tend to show marked epidermotropism, in contrast to the subtle clinical features. The loss of melanocytes is probably due to a direct cytotoxic effect of the CD8+ tumour cells. 

There are five main principles of treatment: 1) Stop the infection with chemotherapy 2) Treat reactions and reduce the risk of nerve damage 3) Educate the patient to cope with existing nerve damage, in particular anaesthesia 4) Treat the complications of nerve damage 5) Rehabilitate the patient socially and psychologically.

Antibacterial treatment for leprosy is highly effective. Drugs recommended are dapsone, rifampicin, and clofazimine. Other drugs with significant activity against M. leprae include ofloxacin, minocycline and clarithromycin, but none of these are as active as rifampicin; at present they should be reserved as second-line drugs for leprosy. A single-dose triple-drug combination (rifampicin, ofloxacin and minocycline) has been tested in India for patients with single skin lesions; although the single dose treatment is less effective than the conventional 6-month treatment for paucibacillary leprosy, it is an operationally attractive field regimen and has been recommended for use by the WHO.

A three-drug regimen [Rifampicin – Dapsone – Clofazimine]   is recommended for multibacillary leprosy (lepromatous, borderline-lepromatous, and borderline leprosy) and a two-drug regimen [Rifampicin – Dapsone] for paucibacillary leprosy (borderline-tuberculoid, tuberculoid, and indeterminate).

Multibacillary leprosy should be treated for 24 months. The recommended length of treatment for multibacillary patients has dropped from 24 months to 12 months by some. There was no controlled trial data to guide this decision, but the classification of multibacillary patients had been widened, so some patients who would previously have received paucibacillary treatment for 6 months are now receiving multibacillary treatment for 12 months. Increased doses of clofazimine 100 mg 3 times daily for the first month with subsequent reductions, are also useful but may take 4–6 weeks to attain full effect.

Paucibacillary leprosy should be treated for 6 months. If treatment is interrupted the regimen should be recommenced where it was left off to complete the full course.

New proposals include testing a common 6-month regimen of dapsone, clofazimine and rifampicin for all patients. This would simplify leprosy treatment but would give some patients a third drug that they do not need, and under-treat patients with a high bacterial load.

Neither the multibacillary nor the paucibacillary antileprosy regimen is sufficient to treat tuberculosis.

Treatment should be continued unchanged during both type I and type II (erythema nodosum leprosum) reactions. During type I reactions neuritic pain or weakness can herald the rapid onset of permanent nerve damage. Treatment with prednisolone (initially 40–60 mg daily) should be instituted at once. However, some patients with active neuritis will develop permanent nerve damage despite treatment with prednisolone. Mild type II reactions may respond to aspirin. Severe type II reactions may require corticosteroids; thalidomide is also useful in men and post-menopausal women who have become corticosteroid dependent, but it should never be used in women of child-bearing potential (significant teratogenic risk).

Treatment of Lucio’s phenomenon includes the standard multidrug therapy for lepromatous leprosy (rifampicin, clofazimine and dapsone). Control of infection and attention to fluid and electrolyte balance are important. Prednisolone may be required to control the reaction. It fails to respond to thalidomide. Response to treatment is often reported as poor, with severe morbidity and frequent deaths, but numbers of reported cases are small. Plasmapheresis reported as helpful in unremitting patients.

*Gohar A.  Borderline lepromatous leprosy with type 1 (downgrading) reaction. Clinical and Experimental Dermatology 2014, 39: 228.

This page was last updated in December 2018.

Saturday, 14 July 2012

Treatment of neonatal cephalic pustulosis

The neonatal or newborn period is the first 4 weeks of extrauterine life.

Patients with neonatal cephalic pustulosis (NCP) have been previously diagnosed as having neonatal acne. NCP is a pustular eruption arising on the face and/or scalp of neonates. Some believe that the two conditions are variants of the same process and actually it can be hard to distinguish between the two conditions at times. NCP lesions (comedonal lesions are not usually seen) typically appear around 2 weeks of age and usually resolve spontaneously in about 2 months. Infantile acne is much less common and usually presents later than neonatal acne/NCP at 3–6 months of age but has been reported as late as 16 months (such acne can be more severe and persistent).

It has been postulated that NCP develops in association with Malassezia species (though not all neonates with this clinical presentation have detectable Malassezia in the lesions). NCP might be related to an overgrowth of lipophilic yeasts at birth that results in an inflammatory reaction leading to monomorphic papules and pustules in predisposed neonates with more sebum production. At least some of the Malassezia-negative cases may have “genuine neonatal acne”, which is generally distinguished by the concurrent presence of comedones (when needed, patients are treated topically with benzoyl peroxide at the lowest strength possible to avoid irritation). In infants with inflammatory acne, oral erythromycin is used. In cases of erythromycin-resistant acne, oral isotretinoin can be given.

Treatment is often not required for this self-limiting disorder. If the condition persists and/or is widespread and unsightly, topical antifungal cream for 15 days helps to shorten the duration of lesions.

This page was last updated in December 2015.

Friday, 6 July 2012

Recurrent aphthous stomatitis (RAS)

Recurrent aphthous stomatitis (RAS) is characterized by recurrent episodes of aphthae [painful ulcers] (Gk, aphtha an eruption in the mouth), each episode lasts from 1 to 4 weeks and the degree of pain varies from mild to extreme. RAS is usually idiopathic and self-limiting. It now seems likely that there is a minor degree of immunological dysregulation underlying aphthae.

RAS is common and affects at least 20% of the population and only in some patients there are identifiable predisposing factors e.g. genetic factors, drug reactions such as nicorandil (nicorandil is a potassium-channel activator with a nitrate component, has both arterial and venous vasodilating properties and is licensed for the prevention and long-term treatment of angina, the mechanism by which nicorandil produces oral ulceration is unclear, there may be a direct local toxic effect of nicorandil on the oral mucosa, nicorandil or a metabolite may be secreted in saliva and similarly produce a toxic effect or alternatively the oral ulcers could be a manifestation of a hypersensitivity reaction to it, the ulcers in such circumstances lack the erythematous halo and the yellow floor typical of aphthous ulcers), deficiencies of iron, folic acid or vitamin B12, HIV infection, Behçet’s syndrome, Sweet’s syndrome, and Crohn’s disease.

RAS may be precipitated by stress, trauma, certain foods, certain toothpastes containing sodium lauryl sulphate (sodium lauryl sulphate is a detergent and wetting agent, and is used in medicated shampoos and in toothpastes, prolonged exposure to it may irritate the skin or mucous membranes), menstruation (hormone therapy may be required) and cessation of smoking.

There are three main clinical types of RAS.

Minor aphthous ulcers (80% of all RAS): These are the commonest type.  They occur mainly in the 10 to 40-year age group, and often cause minimal symptoms. Only a few ulcers (one to six) appear at a time; they heal within 14 days and recur at variable intervals. They become less frequent with age. They are  < 10 mm in diameter. The buccal sulcus is a common site. The ulcer floor is initially yellowish but becomes greyish as epithelialisation proceeds. There is an erythematous halo and some oedema but the ulcers heal with little or no evidence of scarring.

Major aphthous ulcers (10% of all RAS): These are larger, recur more frequently, last longer and are more painful than the minor aphthous ulcers.  They appear on any area of the oral mucosa. They are ≥ 10 mm in diameter with considerable pain and they may heal with scarring (in about 60%).

Herpetiform ulcers (10% of all RAS): They tend to occur in patients in their 3rd decade and there is a female predominance. They are often extremely painful. They heal within 14 days but the ulceration may be virtually continuous. They appear on any area of the oral mucosa. Ventrum of tongue is a common site. They begin with vesiculation, which passes rapidly into multiple (up to 100), minute, discrete ulcers. The ulcers increase in size and coalesce to leave large ragged ulcers and they may heal with scarring (in about 30%). Their similarity to herpetic stomatitis gives herpetiform ulcers their name, but there is no evidence that herpes simplex virus is involved.

RAS in most patients resolves or abates spontaneously with age. An underlying, identifiable predisposing factor is particularly likely where RAS commences or worsens in adult life.

Always palpate solitary long-standing non-healing ulcers to check for the induration and if indurated consider biopsy to exclude or confirm oral cancer.

Predisposing and precipitating factors should be corrected when possible.  Good oral hygiene should be maintained.  Use of chlorhexidine mouthwash is often beneficial and may accelerate healing of recurrent aphthous ulcers.

Topical corticosteroid therapy may be used for aphthous ulcers and it is most effective if applied in the ‘prodromal’ phase. Thrush or other types of candidiasis are recognised complications of corticosteroid treatment. Systemic corticosteroid (e.g. prednisolone) may be required at times.

The main indication for a topical local analgesic (e.g. lidocaine 5% ointment or lidocaine 10% spray) is to relieve the pain of otherwise intractable oral ulceration. When local anaesthetics are used in the mouth care must be taken not to produce anaesthesia of the pharynx before meals as this might lead to choking. Choline salicylate dental gel has some analgesic action and may provide relief for recurrent aphthae (for patients > 16 years of age), but excessive application or confinement under a denture irritates the mucosa and can itself cause ulceration.
Doxycycline rinsed in the mouth may be of value for recurrent aphthous ulceration. A 100 mg doxycycline dispersible tablet can be stirred into a small amount of water then rinsed around the mouth for 2–3 minutes 4 times daily usually for 3 days; it should preferably not be swallowed.  Doxycycline stains teeth, avoid in patients < 12 years of age. Oral low-dose tetracyclines may be required at times.
Rebamipide, an amino acid derivative of 2(1H)-quinolinone, is stated to possess cytoprotective properties and has been shown to be effective in treating RAS (course up to 2 weeks) and Behçet's syndrome (longer course). The usual oral dose is 100 mg three times daily.

Buccal bio-adhesive tablet containing amlexanox can also be used for patients ≥ 12 years of age. It is actually a 2-mg biodegradable oral disc designed to deliver amlexanox. It can be used four times daily after meals and before bed. Up to three bio-adhesive tablets may be used at one time. Contact dermatitis reactions have been described with amlexanox so hands must be washed immediately after applying amlexanox directly to the ulcers with the fingertips. Amlexanox has a stabilising action on mast cells resembling that of sodium cromoglicate and also acts as a leukotriene inhibitor. It is used here as an anti-inflammatory preparation.  

Calcineurin inhibitors e.g topical tacrolimus may be effective.

There are multiple, other therapies available for RAS. Colchicine and pentoxifylline for example, may have a role in individual cases but are not generally very effective or have adverse effects. Thalidomide, in doses from 50 mg up to 300 mg daily, can frequently induce remission, especially in major aphthae, but its important teratogenic effects and the risk of neuropathy must be considered. Other examples include dapsone, sodium cromoglicate, and levamisole.

This page was last updated in April 2014.  

Tuesday, 3 July 2012

Treatment of cradle cap

This type of scaling is very common, particularly on the vertex, during the first few weeks of life, and is generally believed to represent persisting vernix. It may form when a mother refrains from cleaning an infant’s head during bathing for fear of injuring the “soft spot”. Such scaling may appear in early infancy in babies in whom the scalp was clear at birth. To some, this is a form of infantile seborrhoeic dermatitis; to others, it is a different entity. The scalp should be regularly oiled with coconut oil (in the more refractory case, water-dispersible bland emollient should be massaged into the scalp once or twice a day), left for several hours, and then rinsed out using a mild shampoo (soap should be avoided). After washing, a topical anti-yeast agent should be given, such as 2% ketoconazole cream. The scalp can be cleaned with 2% ketoconazole shampoo (it may cause some scalp irritation, not recommended by some) but shampoos containing selenium sulphide and applications containing salicylic acid or corticosteroids, should not be used on the scalp in neonates because of the dangers posed by their percutaneous absorption. Treatment should be applied for 10–14 days.

This page was last updated in November 2013.

Main Works of Reference List (The first eight are my top favourites)

  • British National Formulary
  • British National Formulary for Children
  • Guidelines (BAD - BASHH - BHIVA - Uroweb)
  • Oxford Handbook of Genitourinary Medicine, HIV, and Sexual Health
  • Oxford Handbook of Medical Dermatology
  • Rook's Textbook of Dermatology
  • Simple Skin Surgery
  • Weedon's Skin Pathology
  • A Concise Atlas of Dermatopathology (P Mckee)
  • Andrews' Diseases of the Skin
  • Andrology (Nieschlag E FRCP, Behre M and Nieschlag S)
  • Bailey and Love's Short Practice of Surgery
  • Davidson's Essentials of Medicine
  • Davidson's Principles and Practice of Medicine
  • Fitzpatrick's Colour Atlas and Synopsis of Clinical Dermatology (Klaus Wolff FRCP and Richard Allen Johnson)
  • Fitzpatrick’s Dermatology in General Medicine
  • Ganong's Review of Medical Physiology
  • Gray's Anatomy
  • Hamilton Bailey's Demonstrations of Physical Signs in Clinical Surgery
  • Hutchison's Clinical Methods
  • Lever's Histopathology of the Skin
  • Lever's Histopathology of the Skin (Atlas and Synopsis)
  • Macleod's Clinical Examination
  • Martindale: The Complete Drug Reference
  • Oxford Handbook of Clinical Examination and Practical Skills
  • Oxford Textbook of Medicine
  • Practical Dermatopathology (R Rapini)
  • Sexually Transmitted Diseases (Holmes K et al)
  • Statistics in Clinical Practice (D Coggon FRCP)
  • Stockley's Drug Interactions
  • Treatment of Skin Disease: Comprehensive Therapeutic Strategies
  • Yen & Jaffe's Reproductive Endocrinology