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URTICARIA AND RELATED DISORDERS

Etiology and pathogenesis

The immune system has a complex task to perform. It fights off bacteria, viruses, and fungi, and yet it is supposed to leave the normal bodily tissue alone. Sometimes, the immune system fails to distinguish between self and non-self, and an autoimmune disease results. Many skin diseases can be said to fit into this category, including psoriasis, lichen planus, and some cases of urticaria. In the case of acute urticaria, the immune system is often using IgE-mediated mechanisms to attack transient things, such as food, medications, or viruses, and can thus be termed allergic urticaria. However, many cases of urticaria are not truly allergic, for example physical urticarias (Table 9.1) and some other non-immunologic urticarias (e.g. those due to some drugs, such as salicylates, radiocontrast media, and opiates).

    The mechanism of wheal formation in urticaria typically involves the release of histamine, a vasoactive substance, from mast cells. Other changes in urticaria are due to other vasoactive substances, such as prostaglandins, and these changes may not respond to antihistamines. This explains why wheals may be prevented by antihistamines but erythema still occurs. In the usual urticaria, there is no damage to the vessels and the wheal resolves within 24h. If the blood vessels are damaged, the lesions persist beyond 24h and the term urticarial vasculitis is used.

    The list of potential causes of urticaria is endless; some are apparent from the names of the individual disorders discussed (e.g. cold urticaria), others are discussed in the relevant sections. It is important to recognize that, other than in the case of episodic short-lived episodes of urticaria, a cause is often not apparent.

    Solar urticaria is discussed in Chapter 17.

Dermatographism

Clinical

Patients with dermatographism develop linear wheals at the site of stroking of the skin (Fig.9.1). Sometimes they note raised, red lines that occur soon after scratching, but some present with the chief complaint of intense itching and claim that there is no rash. Dermatographism may occur in various clinical situations, including the third trimester of pregnancy or after treatment for scabies, although, particularly when it is the sole morphology of urticaria, it is commonly idiopathic. The diagnosis may be established by taking a tongue blade and stroking it several times across the back. Immediate redness will occur in most people, but true whealing will develop within minutes in patients with dermatographism. A dermatographometer can grade the pressure used to stroke the skin. Stroking the skin with a pressure of 3.5 * 105 Pa gives a positive result.

Treatment

As in any urticaria, a search for an allergen (e.g. recent antibiotic or infection) should be performed and, if found, eliminated. Most of the time, however, no allergen is found. Antihistamines are effective, with the non-sedating ones least objectionable to the patient (e.g. cetirizine 10mg/day). Some advocate the addition of an H₂blocker for dermatographism, but its effect appears minimal. Interestingly, the H₂blocker famotidine has been reported to cause dermatographism.

Acute urticaria

Clinical

Urticaria of less than 6 weeks’ duration is considered acute urticaria. If the duration is longer than 6 weeks, the term chronic urticaria is used. The deeper swellings of angioedema commonly accompany urticaria.

    Itchy, edematous, raised, pink plaques without scale that move and change daily are characteristic of ‘ordinary’ acute or chronic urticaria (Fig.9.2). Annular lesions resulting from central clearing and white halos (like the Woronoff ring of psoriasis) can occur due to vasoconstriction (Fig.9.3). Persistence of urticaria for more than 24h in the same location, or the presence of associated purpura, may indicate urticarial vasculitis (discussed later in this chapter). If there is any doubt about urticarial vasculitis, lesions should be circled and reexamined 24h later. If the lesions are still in the circle, the patient may have urticarial vasculitis, although other diseases, such as erythema multiforme, should also be considered.
Causes, investigation, and treatment of acute or chronic urticaria Table 9.2 lists the commonest categories of agents that cause urticaria (excluding physical urticarias). The physical urticarias should be excluded as the primary lesion. Delayed pressure urticaria and dermatographism may accompany urticaria. The diet, over-the-counter products, recent infections, and medication history should be analyzed for any new potential allergens. The history may give useful clues; for example, most allergy to foods in adults relates to intermittently ingested items, and causes occasional brief episodes of rash lasting just a day or two. By contrast, presumably due to the immune response being activated and then gradually waning, urticaria triggered by infections typically lasts for several weeks.

    Many would recommend that ‘routine’ screening tests are unlikely to be helpful in acute urticaria, other than to confirm suspicions from the clinical history (such as radio-allergo-sorbent test, RAST, to confirm a suspicion of allergy to shellfish, or serology to confirm a recent viral infection). This is because much urticaria is self-limiting over a couple of months, and also because the yield from non-directed tests is low.

    If the urticaria becomes chronic, laboratory data may be obtained. The first set of tests may include complete blood count (CBC), antinuclear antibody (ANA), renal function, urine analysis, serum glutamate pyruvate transaminase (SGPT), creatinine, and hepatitis B and C serology. If these are unfruitful and the symptoms persist, the following might be helpful: cryoglobulins, chest radiography, complement C3 and C4, dental examination, stool for ova and parasites, biopsy, food diary, sinus radiographs, food elimination diet, and treatment for Helicobacter pylori. A simple food elimination diet is rice and water.

    Some of the main triggers of urticaria are discussed in more detail here.

Food allergens

Food allergens have long been considered potential causes of urticaria. The exact incidence varies from 2 to 30% but is more likely to be lower in the range. Common potential offenders include fruits, nuts, eggs, soybeans, wheat, fish, seafood, tea, and food additives such as aspartame. Other rare cases have included caffeine (coffee and chocolate), ketchup, spices, vanilla, and peanut oil.

    Diagnosis may be made by history, food diary, food elimination diet, and food challenge. Skin testing using the skin prick test may or may not be helpful. RAST is less beneficial but may be utilized. The gold standard for diagnosis of food allergy is a positive placebo-controlled oral challenge test.

    Avoidance is the best treatment, with antihistamines as adjunctive therapy. Desensitization to food is not currently possible.

Food pseudoallergens

Note that several food constituents, such as salicylates, benzoates, or colorings, may act as so-called pseudoallergens that may cause or aggravate urticaria, causing mast cell degranulation by non-immunologic mechanisms (salicylates may also cause IgE-mediated immunologic urticaria). Some of these occur naturally, others are additives. Although probably not a major factor, their importance is threefold:

 •   they may occur in many different foods, and are therefore not suspected as a trigger;
 •   they do not give positive results on immunologic tests, or reliable results on skin tests; and
 •   their influence tends to be dose-related, therefore may vary from day to day.

    While challenge tests to some of these are available, a period of dietician-supervised restriction of these agents can be worth trying for a few weeks. This is mainly applicable to those with chronic urticaria without other likely causes identified, and is likely to be capable of interpretation only if episodes are sufficiently frequent (at least every week) for an impact to be apparent.

Infection

Undoubtedly, various infections can cause urticaria, but the incidence is probably lower than the values given in early estimates, and the type of infection that can cause urticaria varies from region to region.

    Examples include intestinal infection with Citrobacter fructei, as manifested by diarrhea; scabies; Strongyloides stercoralis associated with eosinophilia; giardiasis; Toxocara canis; cytomegalovirus; and hepatitis C. Chronic dental infection has in the past been felt to be a signi?cant etiologic factor, but treatment of these foci usually does not improve the urticaria. Recently, H. pylori has been implicated.

    In one study from France, 65% of patients with chronic urticaria versus 21% of control subjects had antibodies to T. canis. These patients were more likely to be in contact with pets. Some of them were cured or improved with thiabendazole or ivermectin treatment.

    If H. pylori is suspected or implicated (e.g. by 13C urea breath test), treatment may consist of, for example, amoxicillin 500mg four times daily plus oral omeprazole 40mg/day over a period of 2 weeks, followed by omeprazole alone for another 2 weeks. However, many studies do not show a clear difference in the frequency of H. pylori seropositivity in patients with urticaria compared with the background population frequency.

Medications

A huge number of medications may provoke urticaria. It is important to remember over-the-counter agents: aspirin can exacerbate chronic urticaria in a percentage of patients; other examples include multivitamins and wheat bran bath.

Sex

Urticaria developing after sex may occur in latex-sensitive patients after either partner uses a latex-containing condom. Rarely, a woman may react to her partner’s semen.

Treatment

If a cause has been identified, then it should obviously be avoided (if possible). All patients should be instructed to avoid angiotensin-converting enzyme (ACE) inhibitors, aspirin, and other non-steroidal antiinflammatory medications, as these may exacerbate the urticaria. If the patient has had urticaria for months, or even years, and no obvious cause has been found, it is reasonably likely that an autoantibody is causing the mast cell degranulation. If so, the disease is unlikely to remit.

    The foundation of therapy is antihistamines, with the newer, second-generation antihistamines being preferred, as they have lower sedating potential. These include (adult doses) cetirizine (10mg/day), levocetirizine (5mg/day), fexofenadine (120-180mg daily), loratadine (10mg/day), desloratidine (5mg/day), acrivastine (8mg t.d.s.), and mizolastine (10mg/day). First-generation antihistamines are most helpful at night to help with sleep, for example chlorpheniramine 4mg, hydroxyzine 10-25mg, or doxepin 25-50mg (the latter has the potential advantage of H₂as well as H₁ blockade).

    Pure H₂ blockers(e.g. cimetidine) may be given in conjunction with H₂blockers, but the additional benefit is usually small. Similarly, avoidance of pseudoallergens may be tried; the best approach is strict avoidance for a few weeks, but abandoning the idea unless there is clear benefit.

    Prednisone (30-60mg/day) has been used in severe cases but is not something that can be continued for this condition, which often lasts years.

Acute urticaria in children

Clinical

In infants aged less than 6 months, urticaria is caused by allergy to cow’s milk in 75%. For those aged 6-24 months, reactions to drugs (5-aminosalicylic acid, ASA, or amoxicillin) or to viral infections (e.g. hepatitis) are most common. Other causes include foods (milk, peanuts, seafood, and eggs), insect stings (e.g. bees and wasps), and bacterial infection (e.g. streptococci).

Treatment

Elimination of the offending agent if possible, plus diphenhydramine, hydroxyzine, or another antihistamine is appropriate (many adult antihistamines are either unlicensed in children or are unavailable in a suitable formulation, and the sedative effect of antihistamines is less limiting).

Chronic idiopathic urticaria

Clinical

It has been estimated that 15-20% of people will develop urticaria at least once in their lifetime. Many of these episodes will resolve within 6 weeks, but some will persist. In those cases where the urticaria lasts longer than 6 weeks and the cause is unknown, the term chronic idiopathic urticaria is used. The use of this term implies that physical urticarias (e.g. immediate dermatographism, delayed pressure urticaria, solar cholinergic urticaria, and cold urticaria) as well as urticarial vasculitis have been excluded. Mucosal angioedema may be associated.

    Some patients have urticaria for years, seemingly unrelated to any allergen. Most large studies suggest that about one-third of these patients may have autoimmune mast cell disease in which an IgG autoantibody is directed against IgE or against the alpha chain of the IgE high-affinity receptor. Although research is still ongoing, current studies indicate that patients with chronic idiopathic urticaria are more likely than control subjects to have antithyroid autoantibodies, but not to have thyroid disease.

Treatment

See earlier text.

PRACTICE POINTS

Aquagenic urticaria

Etiology and pathogenesis

Aquagenic urticaria is a rare physical urticaria in which urticaria develops after exposure to water. The lesions develop within 30min of exposure. Patients with both aquagenic urticaria and cholinergic urticaria have been described.

Clinical

Urticarial wheals similar to those of cholinergic urticaria develop within 30min of exposure to water, irrespective of temperature (e.g. washing one’s hands, rain, or taking a bath). Sweat, saliva, and tears may induce the condition. Lesions persist for minutes to an hour. Usually the upper body is affected.

Differential diagnosis

Several other physical urticarias may be in the differential, highlighting the need for a careful history. These include the following.

 •   Cholinergic urticaria-due to hot water.
 •   Cold urticaria-triggered by cold water.
 •   Dermatographism-due to shower jets, or to toweling dry after water exposure.
 •   Heat urticaria-less common, due to hot water.

     Non-urticarial water-related causes of itch include the pruritus of polycythemia rubra vera (after exposure) and aquagenic pruritus, a condition in which intense itching (without urticaria) occurs after contact with water of any temperature.

Treatment

Daily antihistamine use may be the best approach. PUVA was successful in one patient with aquagenic urticaria and polymorphous light eruption (PMLE). Preapplication of a barrier cream or ointment (e.g. petrolatum) can prevent development of the lesions.

Cholinergic urticaria

Etiology and pathogenesis
Cholinergic urticaria refers to a unique type of urticaria in which small wheals erupt in relationship to sweating. This may be due to exercise, or due to external heat (e.g. a warm bath). One study of two men with cholinergic urticaria associated with hypohidrosis revealed histologic evidence of occlusion of the superficial acrosyringium. The researchers hypothesized that such a hypohidrosis due to occlusion of superficial sweat ducts may also play a role in other patients with cholinergic urticaria. Of note, cholinergic urticaria in these patients was exacerbated in winter, when sweating is not a frequent event.

Clinical

Urticarial papules, 1-4mm in size, which occur within minutes of exercise, are characteristic (Fig. 9.4). In severe cases, they may be confluent, giving the skin a peau d’orange appearance. The patient can be made to exercise to the point of sweating to establish the diagnosis.

Differential diagnosis

This depends on the trigger; see earlier text for the differential diagnosis of urticaria involving warm water. More commonly, the trigger is exercise; this can sometimes aggravate ordinary urticaria, but postprandial or food-dependent exercise-induced anaphylaxis may also need to be considered. There are several types of exercise-induced urticarias or anaphylaxis, some of which are induced by certain specific foods followed by exercise and some by any food followed by exercise. The urticarial lesions in these conditions have a more typical urticarial morphology (i.e. are larger than lesions of cholinergic urticaria), and of course the patients progress to anaphylaxis.

Treatment

Antihistamines may be used prior to exercise in an attempt to ward off an attack, but this approach is not always successful. Some patients must reduce the amount they sweat to a minimum. If there is evidence that hypohidrosis is associated, for example in wintertime, a trial of frequent exercise or sweating to reduce symptoms may be tried.

Cold urticaria

Etiology and pathogenesis

Cold urticaria is a condition in which urticaria develops after exposure to the cold. It has been associated with acute viral infection, syphilis, drugs (e.g. penicillin, oral contraceptives, and griseofulvin), and HIV infection.
It may be familial, presenting in infancy. Most cases are sporadic and idiopathic. Anaphylaxis may be associated. One study of children with acquired cold urticaria found a high association with asthma and allergic rhinitis, and a family history of atopic diathesis.

Clinical

Lesions may occur at any site that is exposed to cold, such as the fingers (Fig.9.5). Fullness of the throat or swelling of the lips may occur with drinking cold liquids or eating ice cream. Swelling of the head, face, and ears may occur after coming indoors from the cold. Patients can drown if they swim in cold water, due to massive histamine release causing shock.

Differential diagnosis

The differential of water-triggered urticaria has already been discussed. Patients in whom the main trigger is cold wind may have swelling of exposed parts that resembles angioedema (see later in this chapter). To support the diagnosis, the ice cube test is performed as follows. Apply two ice cubes wrapped in thin foil or plastic (so as not to induce aquagenic urticaria) to the forearm for 10min. Watch for whealing minutes after removal (Fig. 9.5). The presence of cryoglobulins, cryofibrinogens, and cold agglutinins should all be excluded. Familial cold autoinflammatory syndrome, formerly known as familial cold urticaria, is a rare condition characterized by fever, rash, and arthralgias elicited by exposure to cold.

Treatment

Antihistamines, both sedating and non-sedating, may be helpful. For example, desloratidine 5-10mg/day was effective in a study of 12 patients. The combination of cetirizine 10mg/day and zafirlukast 20mg b.i.d. was more effective than either agent alone in one patient. The patient should be warned about the risks of anaphylaxis. Specific mention of the dangers of swimming or bathing in cold water should be discussed. An adrenaline (epinephrine) autoinjector may be prescribed.

    Some patients are able to achieve desensitization by immersing parts of the body in cold water in turn, allowing the urticaria response to settle between each immersion (to avoid whole-body urticaria and the risk of histamine shock). This approach relies on the fact that there is a finite time for mast cell granules to re-form; the desensitization needs to be maintained with daily cool baths.

Delayed pressure urticaria

Etiology and pathogenesis

This condition is provoked by prolonged pressure; typical triggers include carrying a heavy bag (affects hands), prolonged walking or standing (feet), or tight clothing. It may coexist with other physical urticarias.

Clinical

The most important feature of this condition, as implied in its name, is the delay in onset of symptoms, often 6-8h. It may also produce deep swelling at acral sites. In both of these respects, it therefore differs from most other urticarias.

Differential diagnosis

The two clinical factors just mentioned may mean that urticaria, and the relevance of the provocative stimulus, may not be suspected. The main differential is that of angioedema and disorders that mimic it (discussed later).

Treatment

Antihistamines should be tried but are often of limited benefit. Oral corticosteroids are helpful but usually only at doses that are unacceptable for long-term use. Avoidance of triggers is the best option.

Contact urticaria

Etiology and pathogenesis

Contact urticaria is usually mediated through IgE antibodies directed against protein peptides. It is more common in atopic individuals, and the classic situation involves the hands in response to contact either with specific foods or with latex. Note that some foods may cross-react with latex (Table 9.3) - particularly if there is a history of reaction to foods,
it is worth sending a RAST for latex even if latex itself is not clinically suspected as a cause of contact urticaria, as the food reaction may be a clue to latex allergy. Ingestion of offending foods can also cause otolaryngeal symptoms.

    Latex allergy is particularly common in healthcare workers, who may be regularly exposed to sources of latex (Table 9.4); is more common in women than in men; and is more common in those with preceding hand dermatitis.

Clinical

The affected skin develops a wheal and flare after contact with the substance (Fig.9.6). The hands may develop a vesicular or eczematous eruption with significant pruritus. Airborne latex may cause facial urticaria, for example due to powdered gloves.

    The offending substance may be idetified by history, RAST testing, scratch testing, or use test. Anaphylaxis may occur, and so great care must be taken.

Differential diagnosis

This includes the following.

Treatment

Avoidance of the offending substance is indicated. In the case of latex allergy, gloves are a major culprit: alternatives include nitrile, polythene, and PVC.

Angioedema

Etiology and pathogenesis

Angioedema refers to the acute swelling of tissue such as the lips or hands. The accumulation of fluid in the skin occurs at a deeper level than with the wheal of urticaria, although the latter is often associated. Mortality has occurred secondary to respiratory tract involvement. Several types occur, including the following.

 Clinical

Almost any part of the body may be affected, but common sites are the eyes, lips, genitalia, hands, and feet (Fig.9.7). These sites may swell to two or three times their normal size within hours. Resolution may occur that same day or several days later. Itching is usually minimal, but pain may occur if deep swelling occurs at ‘tight’ areas such as the sole of the foot.

Differential diagnosis

The main differential diagnosis issue is distinguishing hereditary angioedema from the other forms. Other differentials include the following.

Treatment

If the patient is on an ACE inhibitor, it should be stopped. Antihistamines should be given as for urticaria (see earlier). Danazol and stanozolol are effective for both the acquired and the inherited types. Acute, life-threatening attacks require more aggressive intervention. Adrenaline (epinephrine) and antihistamines are used for the immediate hypersensitivity type.

Angioedema, hereditary

Clinical

Episodic swelling of areas of the face, extremities, bowel (causing abdominal pain), and upper airway are characteristic. Attacks may be spontaneous, triggered by emotional stress or physical trauma. Inheritance is autosomal dominant. The cause is a congenital defect in C1 esterase inhibitor. The majority of patients have low levels of C1 esterase inhibitor, but some have normal or elevated levels that are functionally inactive. The recurrent colicky abdominal pain results from submucosal swelling of the gastrointestinal tract.

Treatment

Attenuated androgens, especially danazol (which causes a rise in C1 esterase inhibitor levels), are used. The dose is 20-30mg/kg per day, with a maximum dose of 800mg/day. It may be used in children. Oxandrolone is another synthetic anabolic steroid that can be used to treat this condition in children. C1 esterase inhibitor may also be infused for treatment of acute episodes. The antifibrinolytic agents aprotinin, tranexamic acid, and epsilon-aminocaproic acid are useful for prophylaxis and treatment of angioedema, probably by inhibiting plasmin.

Anaphylaxis

Etiology and pathogenesis

Anaphylaxis consists of hypotension (shock), laryngeal edema, and bronchospasm, which may be accompanied by urticaria. Patients with acute urticaria and some facial swelling are somewhat overdiagnosed as having anaphylaxis by emergency services.

     Triggers include the following main areas.

Clinical

The features are discussed earlier.

Differential diagnosis

This includes the following.

     Dermatologists or immunologists may be consulted regarding identification of a cause. Generally, this is either evident from the history due to the close temporal relationship between the trigger and the response (often minutes, rarely more than a few hours), or a cause is never identified. A screening RAST for any suspect foods is safer than prick testing; it is worth including peanut, as it may be used in cooking and the fact that it has been ingested may not be obvious. Rechallenge is dangerous.

Treatment

This is not generally the province of the dermatologist but is briefly summarized here, as it is a rare complication of local anesthetic administration. Basic support includes lying the patient flat, administering oxygen, intubation if required due to laryngeal edema, etc.

    Medications administered for acute management are adrenaline (epinephrine), corticosteroids, and an antihistamine. Adrenaline should be administered intramuscularly to ensure reliable absorption, and may need to be repeated at 5-min intervals depending on response; the adult and adolescent dose is 0.5mg, which equates to 0.5mL of 1:1000 (1mg/mL) solution.

    The other drugs are given intravenously, but take longer to act and may need to be continued for 1-2 days to prevent relapse. For those with repeated episodes or at high risk (e.g. those with severe peanut allergy), self-administration of adrenaline (epinephrine) using prefilled syringes may be taught.

PRACTICE POINTS

Hereditary periodic fever syndromes

Etiology and pathogenesis

Familial Mediterranean fever (FMF), hyperimmunoglobulinemia D periodic fever syndrome (HIDS), and tumor necrosis factor receptor- associated periodic syndrome (TRAPS) are the hereditary periodic fever syndromes. FMF is caused by mutations in the Mediterranean fever gene MEFV, HIDS by mutations in the mevalonate kinase gene, and TRAPS by mutations in the tumor necrosis factor receptor superfamily 1A gene. Impaired function of the encoded proteins-i.e. pyrin in FMF, mevalonate kinase in HIDS, and the p55 tumor necrosis factor receptor in TRAPS-induce a dysregulated cytokine balance.

Clinical

Clinical manifestations are relapsing fever, serositis, arthralgia, myalgia, and miscellaneous forms of rash. In FMF, sharply bordered, 10-15-mm, red urticarial lesions occur, usually on the legs, especially the dorsal feet, over the ankle or over the knee (Fig.9.8). The affected skin is hot, tender, and swollen, resembling erysipelas.

Differential diagnosis

From a dermatologic perspective, the differential is mainly from ordinary urticaria, although drug eruptions or viral exanthems may be considered in those with intermittent symptoms or less specific patterns of rash. Many other differential diagnoses, including lupus erythematosus, Behçet disease, and vasculitides, may need to be considered because of the systemic manifestations.

Treatment

The attacks and complications of FMF can be avoided by lifelong administration of colchicine. HIDS is treated symptomatically. Impaired tumor necrosis factor-a regulation in TRAPS can be treated with etanercept.

Urticarial vasculitis

Etiology and pathogenesis

Urticarial vasculitis (see also Ch.14) is defined as urticarial lesions that persist at the same location for more than 24h. This is most commonly associated with systemic lupus erythematosus (SLE), but also Sjögren syndrome, serum sickness, viral infections (e.g. hepatitis C and infectious mononucleosis), mixed cryoglobulins, a monoclonal IgM gammopathy (Schnitzler syndrome), IgA multiple myeloma, fluoxetine administration, and rarely neoplasm. Hypocomplementemia is common and, when it does occur, the association with SLE is highly likely. In one case, the lesions of urticarial vasculitis were induced by cold exposure, and an IgG was found on serum protein electrophoresis (SPEP).

    Autoantibodies to vascular endothelial cells were found in 82% of patients with urticarial vasculitis and SLE, in 70% of patients with hypocomplementemic urticarial vasculitis, and in 14% of patients with urticarial vasculitis alone. They were found in only 32% of patients with SLE but without urticarial vasculitis.

Clinical

Urticarial lesions lasting more than 24h at any given location are characteristic (Fig.9.9). They may be painful rather than itchy. Diascopy may blanch much of the erythema, but purpura remains. Angioedema may occur. Histology shows a leukocytoclastic vasculitis. Systemic associations have included anemia, arthralgias, abdominal pain, glomerulonephritis, ocular inflammation, and pulmonary disease. Laboratory abnormalities may include elevated erythrocyte sedimentation rate (ESR), decreased complement levels, decreased or absent C1q, and C1q autoantibody. In one study, the C1q autoantibody was found in 100% of patients with hypocomplementemic urticarial vasculitis syndrome (HUVS), in 35% of patients with SLE, and in almost no control subjects.

    Urticarial vasculitis is not a specific disease, but instead a clinical findings that is usually associated with a vasculitis that causes significant permeability of the dermal microvascular system. A search for a cause of the vasculitis should be undertaken. Work-up should include drug history (e.g. dexfenfluramine), skin biopsy, CBC, ANA, rheumatoid factor (RF), ESR, urine analysis, CH50, C3, C4, liver enzymes, hepatitis C serology, cryoglobulins, and SPEP.

Differential diagnosis

The most important differential diagnosis is from ‘ordinary’ urticaria; other issues are making the distinction between normocomplementemic urticarial vasculitis and HUVS, and searching for underlying causes such as SLE.

Treatment

If a specific cause is found, it should be treated directly. Otherwise, prednisone may be used (40-60mg/day initially, then tapered). Azathioprine has been used (e.g. 50-100mg/day). Other steroid-sparing agents include dapsone and hydroxychloroquine. Agents to try if these fail include indomethacin and colchicine. Urticarial vasculitis caused by hepatitis C has responded to interferon-alpha therapy.

Autoimmune progesterone dermatitis

Etiology and pathogenesis

Autoimmune progesterone dermatitis (APD), as the name suggests, is a condition in which the woman develops an immune response to her own circulating progesterone, resulting in a skin eruption.

Clinical

Patients with APD may present with an eczematous eruption, erythema multiforme, urticaria (Fig.9.10), pompholyx-like, or a dermatitis herpetiformis-like rash. In some cases, anaphylaxis has been associated. The key diagnostic feature is that the skin changes tend to occur in the later half of the menstrual cycle and resolve within a day or two of the menses. A significant proportion of patients have a history of oral contraceptive use.

Differential diagnosis

In a woman who develops a cyclic rash with her menstrual cycle, autoimmunity to estrogen should also be considered. Patch and prick skin testing to both estrogen and progesterone may be done for diagnostic purposes. Both atopic and allergic contact dermatitis may also show premenstrual exacerbations.

Treatment

Anovulatory agents should be tried initially. Tamoxifen and buserelin (a gonadotropin-releasing hormone analog) have been successful. Oophorectomy has rarely been done.

White/Cox: Diseases of the Skin, 2ed.(c) 2006, Elsevier Inc. All rights reserved.