Urticaria or nettlerash may be defined as an eruption of transient circumscribed oedematous and itchy swellings which last for a few hours. When the swelling involves parts of the body where the skin is bound down loosely such as the eyelids the swellings may be massive and it can then be termed giant urticaria, but the underlying aetiology is the same. Urticaria is a common disorder, more than one-fifth of the population suffer from it at some time in their lives.
The urticarial wheal is formed by extreme dilatation of skin capillaries which allows serum to escape into the surrounding dermis. On dependent parts of the body red blood corpuscles may also be carried out into the tissues thus giving rise to purpura. Except in these circumstances subsidence of the urticarial wheal leaves no residual change and the absence of damage to the epidermis and lack of desquamation serves to differentiate it from dermatitis. Often the diagnosis of urticaria has to be made from the history as at the time of consultation no wheals are visible and the patient in this part of the world may mistakenly describe the rash as blisters.
Urticarial wheals can be caused by a variety of mediators of which histamine is probably the most common but the release of histamine from tissue mast cells as a result of an allergic reaction accounts for a minority of the clinical cases seen. An urticarial wheal can be produced by the intradermal infection of histamine and tissue histamine may be released by a wide range of substances, some of which like nicotinamide are used therapeutically to cause counter irritation over arthritic joints.
Nettle stings, jelly fish stings and many insect bites cause local urticarial wheals by direct histamine liberation or by tissue damage which releases other mediators of inflammation such as the kinins and prostaglandins.
Immunological mechanisms of urticaria. Anaphylactic reactions often termed Type I are due to the presence of the antibody IgE or reagin. This antibody is passively taken up by mast cells. When there is exposure to the antigen the antigen-antibody reaction occurs on the surface of the mast cells which then release histamine. This mechanism is responsible for the majority of acute urticarial episodes in atopic sufferers and in acute penicillin reactions.
In Type III reactions soluble complexes of antigen and antibody, usually IgG, circulate in the blood stream and precipitate out frequently , in the skin, in the kidney or in blood vessels. This type of reaction is responsible for serum sickness and can be suspected when there are joint swellings, fever, renal changes and a raised ESR. Urticaria after in-fections, disorders such as systemic lupus and the urticaria which may follow x-ray therapy to neoplasms can be explained by this mechanism. It may also be responsible for the urticarial eruptions which complicate parasitic diseases such as hydatid and intestinal worm infections. The estimation of immunoglobulins is thus an important investigation in urticaria of this type.
Acute urticaria. Intense irritation ushers in the eruption of wheals which may occur anywhere on the body surface. Wheals vary in size from 2-3 mm to several centimetres across. Diagnosis may be difficult if they tend to form rings. Wheals last 8—24 hours and fade without trace. Joint swellings, fever and even a palpable spleen and superficial lymph glands can accompany the rash to give a clinical picture which resembles acute rheumatism or glandular fever.
Differential diagnosis. The wheal is such a characteristic sign that diagnosis should be simple. Ringed urticarial wheals may resemble erythema multiforme but the history of transient lesions rather than fixed ones and the intense itching should support the diagnosis of urticaria. Urticarial reactions confined to the shoulders and back should stimulate a search for lice on the scalp or on the underclothes and occasionally scabies can present as urticaria.
Physical types of urticaria
Dermographia (Factitious urticaria). An intensely severe triple response on scratching the skin so that whealing follows 5 minutes after a light scratch or friction with a towel. Asymptomatic dermographia has been found in about 5 per cent of the population, slightly more commonly in women than in men. There are however subjects with dermographia who complain of itching and these may easily be mistaken for allergic types of urticaria, since they don’t associate the wheals with trauma to the skin. Symptomatic dermographia is often associated with emotional tension or even hyperthyroidism and it is important in examining any case of urticaria to carry out a test for dermographia.
Heat and emotion (cholinergic) urticaria is a generalised eruption of small erythematous wheals precipitated by physical exercise, rise in body temperature or emotional tension. This is a disorder of the symphathetic control of sweat glands in which acetylcholine causes the liberation of histamine.
Solar and cold urticaria is an acquired hypersensitivity to actinic light or to cold and manifests itself as urticaria on exposure to sunlight or after bathing in cold water. When heat or cold is the precipitating factor the diagnosis can be confirmed by heating the patient under an electric blanket or immersing a limb in iced water. These conditions are particularly resistant to treatment.
Chronic urticaria. Many patients with acute attacks of urticaria drift gradually with recurrent minor attacks into a state of continuous chronic urticaria and it must be accepted that in the present state of our knowledge the cause of 80 per cent of cases of chronic urticaria remains unknown. In their management the drug history is most important since penicillin still remains a frequent cause and although it frequently produces an acute anaphylactic shock, a much more delayed chronic urticaria of the serum sickness type may occur and persist for many months. Thus the history of taking of penicillin is important. It has long been known that salicylates can precipitate attacks but recent evidence suggests that aspirin is a common cause of chronic urticaria and the discovery that the patient takes an occasional Alka-seltzer may be a vital clue.
Foods come fairly low on the list of causes and food diaries are not particularly helpful in the investigation of chronic urticaria. However food additives such as preservatives of the benzoic acid type and the azo dyes used in colouring food stuffs have recently been shown to cross react very closely with those patients who are aspirin sensitive. Thus patients may be challenged by giving the dyes or benzoic acid and their urticaria exacerbated and they may well benefit considerably from an azo-free diet.
Fungus infections must be excluded as the occasional case of chronic Trichophyton rubrum infection may be associated with urticaria and the treatment of the infection with griseofulvin leads to clearing of the urticaria. Many patients give a positive skin test to Candida and it is worth considering putting a patient on anti-candida therapy in those who react postively but we have not been impressed ourselves with the results of this method.
Lastly emotional stress may be the precipitating factor and patients should be investigated to see whether there is undue anxiety in the background.
Drug therapy in urticaria
Antihistamine drugs which block the cell receptors for histamine are of value in dermographia and in acute and chronic urticaria. There are a large number of antihistamine drugs and it would be wise to learn to use one or two. In theory it should be possible to block the action of histamine in every patient but undesirable side effects prevent very high dosage and in practice success is attained in about 80 per cent. One of the mildest of the antihistamines, hydroxyzine hydrochloride (Atarax) has been shown to be successful in symptomatic dermographia but in the more severe varieties of urticaria a more powerful antihistamine is necessary. Promethazine hydrochloride (Phenergan) has the advantage of long action and a sedative effect and need be given only at night in a dose of 25 to 75 mg. When it is desirable for the patient to keep awake in the daytime, chlorpheniramine maleate 4 mg (Piriton) 6-hourly, cyproheptadine hydrochloride (Periactin) 4 mg or triprolidine hydrochloride (Actidil) 2.5 mg 4 times daily can all be used. In view of the work on Azo dyes antihistamines in highly coloured capsules should be avoided. A useful preparation is a long acting Actidil, Pro-Actidil 10 mg given at night. In children antihistamines may be given in the form of elixirs rather than tablets. Once the urticaria has been controlled the dosage of antihistamine should be maintained for several days and then slowly lowered. In chronic urticaria suppression by antihistamines may be needed for months or years but no toxic effects have been reported. Cyproheptadine hydrochloride (Periactin) if continued for many weeks may cause increase in weight.
Acute urticaria. In very acute urticaria where there may be swelling of the tongue and glottis and peripheral vascular collapse adrenalin 0-5-1 ml of a 1/1000 solution injected intra-muscularly is the treatment of choice and repeated every 2 hours. The use of systemic steroids in the treatment of urticaria is, we believe, unnecessary except in acute allergic crises which may occur in serum sickness and penicillin urticaria. In these circumstances, intravenous hydrocortisone is indicated. Local applications are of little value in the relief of symptoms but a tepid bath may give comfort.
Purpura, like urticaria, is a physical sign and not a disease entity. It indicates the escape of red blood cells through the endothelial walls of dermal capillaries and the most important factor in all forms of purpura is the capillary wall. As long as this remains undamaged platelets can be removed or the blood made incoagulable without resultant purpura, but capillary endothelial cells and platelets are antigenically similar and are often damaged in the same pathological process. For the maintenance of normal capillary permeability vitamin C and calcium ions are necessary. A general increase of capillary weakness can be demonstrated by the Hess test in which a sphygmomanometer cuff is left on the arm for 5 minutes at a pressure of 80 mm Hg, more than 10 petechiae below the cuff show an abnormal fragility.
Any intense dilatation of the capillaries will permit localised purpura and thus it is seen as a complication of urticaria, insect bites and cellulitis, and in many skin eruptions on the legs where the capillary pressure is high.
In most examples of generalised purpura more than one mechanism is at fault and any classification is of necessity arbitrary and incomplete. The following is based on the main pathogenic mechanisms.
1. Congenital defects of capillary wall
Ehlers-Danlos Syndrome. A disorder of elastic tissue in which the skin is easily stretched and the extent of joint movements is abnormally large,
2. Increased vascular permiability
3. Increased vascular fragility
Vascular purpura due to infections, drugs and systemic disease such as uraemia and diabetes.
Textile purpura and itching purpura.
4. Chronic vascular purpura
A number of little understood syndromes with eponymous titles such as Schamberg’s Disease.
5. Purpura due to autoimmune damage to vessel walls
Henoch Schoenlein purpura.
This includes a number of syndromes in which the clinical signs are dependent upon the size of the vessels affected. Purpura is associated with urticarial papules, erythema and nodules which may ulcerate.
6. Purpura due to quantitative deficiency of platelets
This may be idiopathic or secondary to bone marrow depression by drugs, infections, radiation or bone marrow disease such as leukaemia.
7. Purpura due to dysproteinaemias
Disturbances of the plasma proteins may present with purpura mainly affecting the legs and often precipitated by exposure to cold.
8. Purpura due to coagulation disorders.
Acute purpura with fever and malaise is a medical emergency. The purpura especially if it affects the fingers and toes, may possibly be evidence of the syndrome of disseminated intravascular coagulation. This occurs as a complication of gram-negative septicaemia, meningococcal infection, hypoxia or amniotic fluid embolism. The diagnosis can be confirmed by the demonstration of prolonged prothrombin time, thrombocytopenia and hypofibrinogenaemia. Though this syndrome is now being more frequently recognised a more probable cause of fever and vascular purpura is a drug sensitivity which can occur with or without a diminution in platelets.
Purpura as part of an auto-immune disorder can usually be distinguished by the occurrence of a variety of skin lesions. The earliest in most types of vasculitis are urticarial papules which only become purpuric after some hours. In th** majority the Hess test is negative.
Thrombocytopenic purpura whether primary or secondary is likely to present with epistaxis or haemorrhages elsewhere in addition to the purpuric eruption which may be very extensive. The Hess testis usually positive.
Investigations in any case of purpura must include complete blood platelet and bone marrow examinations and estimations of serum proteins and immunoglobulins.
Many of the patients with purpura due to vascular fragility will give no positive findings in the laboratory and, even in those of drug origin, confirmation of the diagnosis is often impossible. Because of their clinical importance the following are worthy of mention.
Senile purpura. Prolonged exposure to sunlight weakens the collagen which supports the superficial dermal blood vessels. In the elderly spontaneous subcutaneous haemorrhages of varying size appear on the backs of the hands and the forearms. The haemorrhages are painless but cause anxiety because of their appearance. In association with senile purpura linear or star-shaped pseudo scars are often seen. Changes in the collagen similar to senile skin are produced by prolonged systemic or topical corticosteroid therapy.
Scurvy. The possibility of scurvy should be considered in any old person living alone and the first symptoms of scurvy are often mental depression and pain and swelling in the legs and ankles. The classical follicular haemorrhages may not be apparent but large ecchymoses, bruises and a curious tender woody feel of the muscles are found.
Purpuric dermatitis or itching purpura. A chronic eruption of papules, scales and purpuric haemorrhages, is seen quite frequently on the lower limbs. This eruption may occur spontaneously but it can also be produced as a contact reaction to clothing, possibly by some chemical used in the finish of cloth. It is also a very recognisable pattern of the drug eruption due to carbromal which, unlike most drug eruptions, persists for many weeks after the drug has been discontinued.