Section 7. Dermatitis/Allergic

A 1-year-old Asian American girl is brought to her family physician for a new rash on her face and legs (Figures 145-1 and 145-2). The child is scratching both areas but is otherwise healthy. There is a family history of asthma, allergic rhinitis, and atopic dermatitis (AD) on the father's side. The child responded well to low-dose topical corticosteroids and emollients.

AD is a chronic and relapsing inflammatory skin disorder characterized by itching and inflamed skin that is triggered by the interplay of genetic, immunologic, and environmental factors.

Eczema, atopic eczema.

• AD is the most frequent inflammatory skin disorder in the United States and the most common skin condition in children.1
• Worldwide prevalence in children is 15% to 20% and is increasing in industrialized nations.2
• Sixty percent of cases begin during the first year of life and 90% by 5 years of age.1 One third will persist into adulthood.2
• Sixty percent of adults with AD have children with AD (Figure 145-3).1

• Strong familial tendency, especially if atopy is inherited from the maternal side.
• Associated with elevated T-helper (Th) 2 cytokine response, elevated serum immunoglobulin (Ig) E, hyperstimulatory Langerhans cells, defective cell-mediated immunity, and loss of function mutation in filaggrin, an epidermal barrier protein.
• Exotoxins of Staphylococcus aureus act as superantigens and stimulate activation of T-cells and macrophages, worsening AD without actually showing signs of superinfection.
• Patients may have a primary T-cell defect. This may be why they can get more severe skin infections caused by herpes simplex virus (eczema herpeticum as seen in Figure 145-4) or bacteria (widespread impetigo). They are also at risk of a bad reaction to the smallpox vaccine with dissemination of the attenuated virus beyond the vaccination site. Eczema vaccinatum is a potentially deadly complication of smallpox vaccination (Figure 145-5).

• History—Pruritus is the hallmark symptom of AD. It is referred to as “the itch that rashes” as patients will often feel the need to scratch before a primary lesion appears. If it does not itch, it is not AD. Persons with AD often have a personal or family history of other allergic conditions, namely asthma and allergic rhinitis.
• The atopic triad is AD, allergic rhinitis, and asthma. Atopic persons have an exaggerated inflammatory response to factors that irritate the skin.
• Physical examination—Primary lesions include vesicles, scale, papules, and plaques.
• Secondary (or sequential) lesions include linear excoriations from scratching or rubbing which may result in lichenification (thickened skin with accentuation of skin lines), fissuring, and prurigo nodularis. Crust may indicate that a secondary infection has occurred. Postinflammatory hyperpigmentation and follicular hyperaccentuation (more prominent hyperkeratotic follicles) (Figure 145-6) may also be identified.

Typical Distribution

• AD often starts on the face in infancy and childhood (Figures 145-1 and 145-7) and then appears in the flexural folds, especially the antecubital and popliteal fossa (Figures 145-8, 145-9, 145-10).
• Involvement of the neck, wrists, and ankles also may occur (Figures 145-11 and 145-12).
• AD in adults can occur on the hands, around the mouth, or eyelids as well as all the other areas (Figures 145-13 and 145-14).
• In one series, the prevalence of hand involvement in patients with active AD was 58.9%. There was a significant trend toward an increasing prevalence of hand involvement with increasing age.3

Other Features or Conditions Associated with Atopic Dermatitis

• Keratosis pilaris (Figure 145-15).
• Ichthyosis (Figure 145-16).
• Pityriasis alba (Figures 145-17 and 145-18).
• Palmar or plantar hyperlinearity.
• Dennie-Morgan lines (infraorbital fold) (Figure 145-14).
• Hand or foot dermatitis (see Chapter 147, Hand Eczema).
• Cheilitis (see Chapter 32, Angular Cheilitis).
• Susceptibility to cutaneous infections (Figures 145-4 and 145-5).
• Xerosis (dry skin) (Figure 145-19).
• Eye findings—Recurrent conjunctivitis, keratoconus (Figure 145-20), cataracts, orbital darkening.
• A horizontal nasal crease may be seen over the bridge of the nose in a patient with allergic rhinitis prone to performing the allergic salute. In some patients this crease may become hyperpigmented (Figure 145-21).

Laboratory Studies

Labs are rarely needed if the history and physical examination support the diagnosis. Occasionally, a KOH preparation may be needed to rule out tinea or a skin scraping to rule out scabies. Of course, both of these conditions can occur on top of AD. RAST (radioallergosorbent test) testing for food allergies and serum IgE levels are not of proven benefit.

• Dyshidrotic eczema—Dry inflamed scaling skin on the hands and feet with tapioca-like vesicles, especially seen between the fingers (see Chapter 147, Hand Eczema).
• Seborrheic dermatitis—Greasy, scaly lesions on scalp, face, and chest (see Chapter 151, Seborrheic Dermatitis).
• Psoriasis—Thickened plaques on extensor surfaces, scalp, and buttocks; pitted nails (see Chapter 152, Psoriasis).
• Lichen simplex chronicus (sometimes called neurodermatitis)—Usually, a single patch in an area accessible to scratching such as the ankle, wrist, and neck (see Chapter 149, Self-Inflicted Dermatoses).
• Contact dermatitis—Positive exposure history, rash in area of exposure; absence of family history. Patch testing may be helpful in distinguishing from AD (see Chapter 146, Contact Dermatitis).
• Scabies—Papules, burrows, finger web involvement, positive skin scraping (see Chapter 143, Scabies).
• Dermatophyte infection—On the hands or feet can look just like hand or foot dermatitis; a positive KOH preparation for hyphae can help make the diagnosis (see Chapter 140, Tinea Pedis).

• There is some evidence suggesting that controlling house dust mites reduces severity of symptoms in patients with the atopic triad. Bedding covers were found to be the most effective method to control dust mites and AD symptoms in this subgroup of AD patients. Unfortunately, dust mite interventions are not proven to be effective for patients with AD that do not have the full atopic triad.1 SOR B
• Dietary restriction is controversial but may be useful for infants with proven egg allergies. SOR B There is insufficient evidence that dietary manipulation in children or adults reduces symptom severity and may cause iatrogenic malnourishment.
• Patient education, avoidance of possible triggers (enzyme-rich detergents, wool clothing), and dry skin care should be optimized.
• Dilute bleach baths (0.5 cup of 6% bleach in tub of bath water) lower the S. aureus burden on the skin, decreasing severity of AD.4 SOR B
• There is some evidence suggesting probiotic treatment of pregnant mother and prolonged nursing of child may delay onset of AD.1 SOR B

Topical Therapies

• Topical steroids and emollients have been proven to work for AD and are the mainstay of treatment.1 SOR A
• Vehicle selection and steroid strength area based on age, body location, and lesion morphology. The ointments are best for dry and cracked skin and are more potent. Creams are easier to apply and are better tolerated by some patients.
• Use stronger steroids for thicker skin, severe outbreaks, or lesions that have not responded to weaker steroids. Avoid strong steroids on face, genitals, and armpits and in infants and small children.
• To avoid adverse effects, the highest potency steroids (e.g., clobetasol) should not be used for longer than 2 weeks continuously. However, they can be used intermittently for recurring AD in a pulse-therapy mode (e.g., apply every weekend, with no application on weekdays).
• Topical calcineurin inhibitors (immunomodulators, such as pimecrolimus and tacrolimus) reduce the rash severity and symptoms in children and adults.1 SOR A These work by suppressing antigen-specific T-cell activation and inhibiting inflammatory cytokine release. These are steroid-sparing medications that are helpful for eyelid eczema and in other areas when steroids may thin the skin (Figure 145-22). These agents are now only approved for persons older than 2 years of age and the FDA states that they should not be used as first-line agents because of a possible risk of causing cancer. The American Academy of Dermatology (AAD) has released a statement that the “data does not prove that the proper topical use of pimecrolimus and tacrolimus is dangerous.”
• Short-term adjunctive use of topical doxepin may aid in the reduction of pruritus.1 SOR A
• Topical and systemic antibiotics are used for AD that has become secondarily infected with bacteria. The most common infecting organism is S. aureus. Weeping fluid and crusting during an exacerbation should prompt consideration of antibiotic use1 (Figures 145-7, 145-8, and 145-23). SOR A

Oral/Systemic Therapies

• For extensive flares, consider oral prednisone or an IM shot of triamcinolone (40 mg in 1 mL of 40 mg/mL suspension for adults).1 SOR C
• The value of antihistamines in AD is controversial. If antihistamines are to be used, the sedating agents are most effective and can be given at night.1 SOR B
• Cyclosporine for severe refractory AD can be used in long-term maintenance therapy to treat and avoid relapse.1 SOR A Cyclosporine is approved for 1 year of lifetime therapy for skin diseases in the United States and 2 years in Europe (Figure 145-24).
• UV phototherapy may also be used in severe refractory AD with some success.1 SOR A
• Azathioprine, methotrexate, and mycophenolate mofetil are of possible benefit, but there is less evidence for their effectiveness.1 SOR C

Patients need to know that scratching their AD makes is worse. Behavior modification is especially challenging in young children and may involve cutting fingernails short and occluding hands/body at night with cotton gloves or clothing. Because of its chronicity and cyclic nature, AD patients may have poor adherence. In one recent study, overall adherence was 32%. A written action plan may be employed to improve adherence (Table 145-1).

Regular follow-up should be given to patients with chronic and difficult-to-control AD. Establishing a good regimen is crucial to good control and then visits may be adjusted to longer intervals between visits.

A 38-year-old woman twisted her right ankle and applied a Chinese medicine patch to relieve the pain. The following day the patient developed a severe contact dermatitis (CD) with many small vesicles (<5 mm) and bullae (>5 mm) (Figure 146-1). The erythema had a well-demarcated border and was traced by the doctor's pen. Cold compresses and a high potency topical steroid were prescribed. When the patient showed little improvement a 2-week course of oral prednisone was given starting with 60 mg daily and tapering down to 5 mg daily. The patient responded rapidly and the CD fully resolved.1,2

CD is a common inflammatory skin condition characterized by erythematous and pruritic skin lesions resulting from the contact of skin with a foreign substance. Irritant contact dermatitis (ICD) is caused by the non-immune-modulated irritation of the skin by a substance, resulting in a skin changes. Allergic contact dermatitis (ACD) is a delayed-type hypersensitivity reaction in which a foreign substance comes into contact with the skin, and upon reexposure, skin changes occur.3

• Some of the most common types of CD are secondary to exposures to poison ivy, nickel, and fragrances.4
• Patch testing data indicate that the five most prevalent contact allergens out of more than 3700 known contact allergens are nickel (14.3% of patients tested), fragrance mix (14%), neomycin (11.6%), balsam of Peru (10.4%), and thimerosal (10.4%).5
• Occupational skin diseases (chiefly CD) rank second only to traumatic injuries as the most common type of occupational disease. Chemical irritants such as solvents and cutting fluids account for most ICD cases. Sixty percent were ACD and 32% were ICD. Hands were primarily affected in 64% of ACD and 80% of ICD4 (Figure 146-2).

• CD is a common inflammatory skin condition characterized by erythematous and pruritic skin lesions resulting from the contact of skin with a foreign substance.
• ICD is caused by the non-immune-modulated irritation of the skin by a substance, resulting in a skin rash.
• ACD is a delayed-type hypersensitivity reaction in which a foreign substance comes into contact with the skin, and is linked to skin protein forming an antigen complex that leads to sensitization. Upon reexposure of the epidermis to the antigen, the sensitized T cells initiate an inflammatory cascade, leading to the skin changes seen in ACD.

History

Ask about contact with known allergens (i.e., nickel, fragrances, neomycin, and poison ivy/oak).

• Nickel exposure is often related to the wearing of rings, jewelry, and metal belt buckles (Figures 146-3, 146-4, 146-5, and 146-6).
• Fragrances in the forms of deodorants and perfumes (Figure 146-7).
• Neomycin applied as a triple antibiotic ointment by patients (Figures 146-8 and 146-9).
• Poison ivy/oak in outdoor settings. Especially ask when the distribution of the reaction is linear (Figures 146-10 and 146-11).
• Ask about occupational exposures, especially solvents. For example, chemicals used in hat making can cause ICD on the hands (Figure 146-2).
• Tapes applied to skin after cuts or surgery are frequent causes of CD (Figure 146-12).
• If the CD is on the feet, ask about new shoes (Figures 146-13 and 146-14).

A detailed history of products used on the skin may reveal a suspected allergen. In Figure 146-15, this truck driver was using baby wipes to clean his skin during long drives. Patch testing ultimately revealed that he was allergic to one of the ingredients in those wipes.

Clinical Features

All types of CD have erythema. Although it is not always possible to distinguish between ICD and ACD, here are some features that might help:

• ICD:
  • Location—usually the hands.
  • Symptoms—burning, pruritus, pain.
  • Dry and fissured skin (Figure 146-2).
  • Indistinct borders.
• ACD:
  • Location—usually exposed area of skin, often the hands.
  • Pruritus is the dominant symptom.
  • Vesicles and bulla (Figures 146-1 and 146-8).
  • Distinct angles, lines, and borders (Figures 146-8, 146-9, 146-10, 146-11, and 146-12).

Both ICD and ACD may be complicated by bacterial superinfection showing signs of exudate, weeping, and crusts.

Toxicodendron (Rhus) dermatitis (poison ivy, poison oak, and poison sumac) is caused by urushiol, which is found in the saps of this plant family. Clinically, a line of vesicles can occur from brushing against one of the plants. Also, the linear pattern occurs from scratching oneself and dragging the oleoresin across the skin with the fingernails (Figures 146-10 and 146-11).

Systemic CD is a rare form of CD seen after the systemic administration of a substance, usually a drug, to which topical sensitization has previously occurred.6

Laboratory Studies

The diagnosis is most often made by history and physical examination. Consider culture if there are signs of superinfection and there is a concern for methicillin-resistant Staphylococcus aureus (MRSA). The following tests may be considered when the diagnosis is not clear.

• KOH preparation and/or fungal culture if tinea is suspected.
• Microscopy for scabies mites and eggs.
• Latex allergy testing—This type of reaction is neither ICD (nonimmunologic) nor ACD. The latex allergy type of reaction is a type I, or immunoglobulin (Ig)E-mediated response to the latex allergen.
• Patch testing—Common antigens are placed on the skin of a patient. The T.R.U.E. Test comes in three tape strips that are easy to apply to the back (Figure 146-16). There is no preparation needed to test for the 29 common allergens embedded into these strips (Table 146-1 for a list of the 29 allergens). The strips are removed in 2 days and read at that time and again in 2 more days (Figure 146-17). The T.R.U.E. Test website provides detailed information on how to perform the testing and how to counsel patients about the meaning of their results. Any clinician with an interest in patch testing can easily perform this service in the office.
  • A metaanalysis of the T.R.U.E. Test shows that nickel (14.7% of tested patients), thimerosal (5.0%), cobalt (4.8%), fragrance mix (3.4%), and balsam of Peru (3.0%) are the most prevalent allergens detected using this system.5
  • Critics of the T.R.U.E. Test state that it misses other important antigens. There are a number of dermatologists who create their own more extensive panels in their office. If the suspected allergen is not in the T.R.U.E. Test, refer to a specialist who will customize the patch testing. Also, personal products, such as cosmetics and lotions, can be diluted for special patch testing.
  • A metaanalysis of children patch tested for ACD showed the top five allergens to be nickel, ammonium persulfate, gold sodium thiosulfate, thimerosal, and toluene-2,5-diamine (p-toluenediamine).7 Only two of these five allergens are in the T.R.U.E. Test, so it may be best to not use this standardized patch testing for children.
  • Once the patch test results are known, it is important to determine if the result is “relevant” to the patient's dermatitis. One method for classifying clinical relevance of a positive patch test reaction is: (a) current relevance—the patient has been exposed to allergen during the current episode of dermatitis and improves when the exposure ceases; (b) past relevance—past episode of dermatitis from exposure to allergen; (c) relevance not known—not sure if exposure is current or old; (d) cross-reaction—the positive test is a result of cross-reaction with another allergen; and (e) exposed—a history of exposure but not resulting in dermatitis from that exposure, or no history of exposure but a definite positive allergic patch test.6
• Punch biopsy—When another underlying disorder is suspected that is best diagnosed with histology (e.g., psoriasis).

• Atopic dermatitis is usually more widespread than CD. There is often a history of other atopic conditions, such as allergic rhinitis and asthma. There may be family history of allergies. However, persons with atopic dermatitis are more prone to CD (Figure 146-6; Chapter 145, Atopic Dermatitis).
• Dyshidrotic eczema—Seen on the hands and feet with tapioca vesicles, erythema, and scale. Although this is not primarily caused by contact to allergens, various irritating substances can make it worse (see Chapter 147, Hand Eczema).
• Immediate IgE contact reaction (e.g., latex glove allergy)—Immediate erythema, itching, and possibly systemic reaction after contact with a known (or suspected) allergen.
• Fungal infections—A dermatophyte infection that can closely resemble CD when it occurs on the hands and feet. Tinea pedis is usually seen between the toes, on the soles or on the sides of the feet. CD of the feet is often on the dorsum of the foot and related to rubber or other chemicals in the shoes (Figures 146-13 and 146-14; Chapter 140, Tinea Pedis).
• Scabies on the hands can be mistaken for CD. Look for burrows and for the typical distribution of the scabies infestation to distinguish this from CD (see Chapter 143, Scabies).
• Allergies to the dyes used in tattoos can occur. Although this is not strictly a CD because the dye is injected below the skin, the allergic process is similar (Figure 146-18).

• Identify and avoid the offending agent(s).4 SOR A
  • Be aware that some patients are actually allergic to topical steroids. This unfortunate situation can be diagnosed with patch testing.
  • In cases of nickel ACD, we recommend the patient cover the metal tab of their jeans with an iron-on patch or a few coats of clear nail polish.
• Cool compresses can soothe the symptoms of acute cases of CD.4 SOR C
• Calamine and colloidal oatmeal baths may help to dry and soothe acute, oozing lesions.3,4 SOR C
• Localized acute ACD lesions respond best with mid-potency to high-potency topical steroids such as 0.1% triamcinolone to 0.05% clobetasol, respectively.4 SOR A
• On areas of thinner skin (e.g., flexural surfaces, eyelids, face, anogenital region) lower-potency steroids such as desonide ointment can minimize the risk of skin atrophy.3,4 SOR B
• There is insufficient data to support the use of topical steroids for ICD, but because it is difficult to distinguish clinically between ACD and ICD, these agents are frequently tried. SOR C
• If ACD involves extensive skin areas (>20%), systemic steroid therapy is often required and offers relief within 12 to 24 hours. The recommended dose is 0.5 to 1 mg/kg daily for 5 to 7 days, and if the patient is comfortable at that time, the dose may be reduced by 50% for the next 5 to 7 days. The rate of reduction of steroid dosage depends on factors such as severity, duration of ACD, and how effectively the allergen can be avoided.4 SOR B
• Oral steroids should be tapered over 2 weeks because rapid discontinuance of steroids can result in rebound dermatitis. Severe poison ivy/oak is often treated with oral prednisone for 2 to 3 weeks. Avoid using a Medrol dose-pack, which has insufficient dosing and duration.4 SOR B
• The efficacy of topical immunomodulators (tacrolimus and pimecrolimus) in ACD or ICD has not been well established.4 However, one randomized controlled trial (RCT) did demonstrate that tacrolimus ointment is more effective than vehicle in treating chronically exposed, nickel-induced ACD.8 SOR B
• Although antihistamines are generally not effective for pruritus associated with ACD, they are commonly used. Sedation from more soporific antihistamines may offer some degree of palliation (diphenhydramine, hydroxyzine).4 SOR C
• Bacterial superinfection should be treated with an appropriate antibiotic that will cover Streptococcus pyogenes and S. aureus. Treat for MRSA if suspected.
• Once the diagnosis of any CD is established, emollients and moisturizers may help soothe irritated skin.4 SOR C

For ICD and occupational CD of the hands:

• Wear protective gloves when working with known allergens or potentially irritating substances such as solvents, soaps, and detergents.6,9 SOR A
• Use cotton liners under the gloves for both comfort and the absorption of sweat. Wearing cotton glove liners can prevent the development of an impaired skin barrier function caused by prolonged wearing of occlusive gloves.9 SOR B
  • There is insufficient evidence to promote the use of barrier creams to protect against contact with irritants.6,9 SOR A
  • After work, conditioning creams can improve skin condition in workers with damaged skin.9 SOR A
• Keep hands clean, dry, and well-moisturized whenever possible.
• Petrolatum applied twice a day is a great way to moisturize dry and cracked skin without exposing the patient to new irritants.

If the CD is severe enough (Figure 146-19), the patient may need to change work to completely avoid the offending irritant or antigen.

May need frequent follow-up if the offending substance is not found, the rash does not resolve and if patch testing will be needed.

Avoid the offending agent and take the medications as prescribed to relieve symptoms.

Patient Resources

• PubMed Health. Contact Dermatitis—http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001872/.
• The T.R.U.E. Test website has a wealth of information on reading labels, common allergens and patch testing for patients—http://www.truetest.com/.

Provider Resources

• American Family Physician. Diagnosis and Management of Contact Dermatitis—http://www.aafp.org/afp/2010/0801/p249.html.
• The T.R.U.E. Test website has a wealth of information on patch testing for healthcare professionals—http://www.truetest.com/.

An Asian American physician presents with dry scaling on her hands. Frequent hand washing makes it worse and it sometimes cracks. She has allergic rhinitis and she had more widespread atopic dermatitis in her youth. This is a case of chronic atopic hand dermatitis (Figure 147-1). The treatment suggested was use of Cetaphil (or equivalent nonsoap cleanser) instead of soap and water. She was directed to soak her hands 3 to 5 minutes in warm water every night, apply triamcinolone 0.1% ointment, and cover with cotton gloves overnight. Her hands cleared 90% with this treatment and she was pleased with the results.

Hand eczema refers to a wide spectrum of inflammatory skin diseases of the hands, including atopic dermatitis, contact dermatitis, pompholyx, and dyshidrotic eczema.

Hand dermatitis, pompholyx, dyshidrotic eczema, vesicular palmoplantar eczema. Although some people use pompholyx and dyshidrotic eczema synonymously, others reserve pompholyx for hand eczema with vesicles and bullae on the palms and dyshidrotic eczema for conditions with smaller vesicles between the fingers and toes.

• The prevalence of hand dermatitis is estimated at approximately 2% to 8.9% in the general population.1

• There are many clinical variants of hand dermatitis and a number of different classification schemas. Here is one accepted classification scheme:

  1. Contact (i.e., allergic and irritant) (Figure 147-2).

  2. Hyperkeratotic (i.e., psoriasiform) (Figure 147-3).

  3. Frictional (Figure 147-4).

  4. Nummular (Figure 147-5).

  5. Atopic (Figure 147-6).

  6. Pompholyx (i.e., dyshidrosis) (Figures 147-7 and 147-8).

  7. Chronic vesicular hand dermatitis.1 (Figure 147-9)

• Another way of looking at hand dermatitis is to break it down into three categories:2

  1. Endogenous—Atopic, psoriasis, pompholyx, dyshidrotic (we do not include psoriasis as a type of hand eczema in this chapter).

  2. Exogenous—Allergic and irritant contact dermatitis.

  3. Infectious—Tinea, Candida, and/or superimposed S. aureus (Figure 147-10).

• Most contact dermatitis of the hands is secondary to irritants such as soap, water, solvents, and other chemicals.
• Allergic contact dermatitis (ACD) is a type IV, delayed-type, cell-mediated, hypersensitivity reaction.
• The nine most frequent allergens related to hand contact dermatitis were identified by patch testing from 1994 to 2004.3 These are quaternium-15 (16.5%), formaldehyde (13.0%), nickel sulfate (12.2%), fragrance mix (11.3%), thiuram mix (10.2%), balsam of Peru (9.6%), carba mix (7.8%), neomycin sulfate (7.7%), and bacitracin (7.4%).3
• Rubber allergens were commonly associated with occupation. One third of patients with ACD had identifiable relevant irritants.3
• Most common allergens are preservatives, metals, fragrances, topical antibiotics, or rubber additives.3

Clinical Features1

Contact (i.e., allergic and irritant) (Figure 147-2).

• Symptoms include burning, stinging, itching, and tenderness at the site of exposure to the irritant or allergen.1
• Acute signs include papules, vesicles, bullae, and edema.
• Weeping and crusting can occur with or without superinfection.
• Chronic signs include plaques with fissuring, hyperpigmentation, and/or lichenification.
• Irritant contact dermatitis may predispose to ACD.

Hyperkeratotic (i.e., psoriasiform) (Figure 147-3).

• Symmetric hyperkeratotic plaques.
• May be localized to the proximal or middle part of the palms.
• Painful fissures are common.

Frictional (Figure 147-4).

• Mechanical factors, often from work, such as trauma, friction, pressure, and vibration, induce skin changes with erythema and scale.
• “Wear-and-tear dermatitis.”1
• Can be caused by contact with paper and fabrics.

Nummular (Figure 147-5).

• Nummular hand dermatitis (also called discoid hand dermatitis).
• Tiny papules, papulovesicles, or “coin-shaped” eczematous plaques.
• Dorsal hands and distal fingers are often involved.

Atopic

• Patients with childhood atopic dermatitis are predisposed to develop hand dermatitis as adults (Figure 147-6).
• There is no characteristic pattern and it can occur on any part of the hand.
• Extension to or involvement of the wrist is common (Figure 147-11).

Pompholyx (i.e., dyshidrosis, dyshidrotic eczema).

• Has recurrent crops of papules, vesicles, and bullae on the lateral aspects of the fingers, as well as the palms and soles, on a background of nonerythematous skin (Figures 147-7 and 147-8).
• These are described as tapioca vesicles as they look like the small spheres in tapioca. The vesicles open and the skin then peels (mild desquamation).
• There may be pruritus or pain.
• Although some use the names pompholyx and dyshidrotic eczema interchangeably, others only use the name pompholyx to describe an explosive onset of large bullae, usually on the palms (Figure 147-8) and dyshidrotic eczema to mainly describe chronic small tapioca vesicles on the sides of the fingers (Figure 147-7).
• Both conditions may last 2 to 3 weeks and resolve, leaving normal skin, only to recur again at varying intervals.
• Both conditions are idiopathic and closely related, if not identical.
• Symptoms may be associated with exogenous factors (e.g., nickel or hot weather) or endogenous factors (e.g., atopy or stress).

Chronic vesicular hand dermatitis (Figure 147-9).

• Chronic vesicles that are mostly palmar and pruritic.
• Differentiated from pompholyx by a more chronic course and the presence of vesicles with an erythematous base.
• The soles of the feet may also be involved.
• Poorly responsive to treatments.
• In one series, 55% of patients with this type of hand dermatitis were found to have positive patch test results.4

Typical Distribution

Of course, hand dermatitis is on the hands, but both hands and feet can be involved in dyshidrotic eczema and chronic vesicular hand dermatitis.

Laboratory Studies

Scraping and using microscopy with KOH (with or without a fungal stain) to look for dermatophytes is helpful (see Chapter 135, Fungal Overview).

Patch testing can be crucial to the diagnosis and treatment of hand eczema. Patch testing is described in detail in the previous chapter (Chapter 146, Contact Dermatitis). The patient in Figure 147-8 had severe pompholyx worsening with topical steroids. Patch testing showed she was allergic to topical steroids (Figure 147-12). Her hands finally cleared with oral cyclosporine and avoidance of all topical and oral steroids.

• Tinea manus is often found as part of the two-foot, one-hand syndrome in which both feet have scaling tinea pedis and one hand has scale as well (Figure 147-13) (see Chapter 135, Fungal Overview, and Chapter 140, Tinea Pedis).
• Candida can be seen in between the fingers with erythema and scale over the fingers and hand (Figure 147-10) (see Chapter 136, Candidiasis).
• Psoriasis often involves the hand. It can present with plaques on the dorsum of hand and over the knuckles of the fingers or on the palm of the hand. Palmoplantar psoriasis will involve the hands and feet (see Chapter 152, Psoriasis).
• Knuckle pads are thickening of the skin over the knuckles. These can be accompanied by hyperpigmentation.

• Lifestyle modifying factors, as listed in Table 147-1, are essential.
• Avoid irritants and “wet work” at home and at work as much as possible. SOR C
• Wear protective gloves when working with known allergens or potentially irritating substances such as solvents, soaps, and detergents.5,6 SOR A
• Use cotton liners under the gloves for both comfort and the absorption of sweat. Wearing cotton glove liners can prevent the development of an impaired skin barrier function caused by prolonged wearing of occlusive gloves.5,6 SOR B

There is insufficient evidence to promote the use of barrier creams to protect against contact with irritants.5,6 SOR A

Applying conditioning creams after work can improve skin condition in workers with damaged skin on the hands.6 SOR A

• Avoid latex gloves because of a high risk of latex allergy among patients with hand dermatitis. SOR C
• Frequent and liberal use of emollients can help restore normal skin-barrier function. Simple, inexpensive, petrolatum-based emollients were found to be equally as effective as an emollient containing skin-related lipids in a 2-month study of 30 patients with mild to moderate hand dermatitis.7 SOR B
• For patients with very dry skin that is not irritated by water, it may help to soak hands 3 to 5 minutes in warm water at night, apply triamcinolone 0.1% ointment, and cover with cotton gloves overnight. The cotton gloves may be used repeatedly even though they will soak up some of the ointment. SOR C
• Do not wash hands with soap. Use Cetaphil, a nonsoap cleanser. SOR C

See Table 147-2 for a summary of the recommended therapeutic agents for different types of hand dermatitis.

Topical Agents

• Topical steroids are first-line agents for inflammatory hand dermatitis. Ointments are considered more effective and contain fewer preservatives and additives than creams. Some patients will prefer a cream vehicle, so that patient preference should be considered in prescribing topical steroids. It is better to have a patient use a cream than not use an ointment.
• Start with 0.1% triamcinolone ointment bid as it is inexpensive and effective. SOR C Cut back on use when possible to avoid skin atrophy, striae, and telangiectasias.
• Topical calcineurin inhibitors, tacrolimus and pimecrolimus, are effective in the treatment of atopic and other allergic types of hand dermatitis.8,9 SOR B Skin burning or an unpleasant sensation of warmth is reported by approximately 50% of patients using topical tacrolimus and 10% with pimecrolimus.10

Phototherapy and Ionizing Radiation

• Psoralen and UVA irradiation (PUVA) has been used to treat patients with all forms of hand dermatitis.10 SOR C
• Grenz rays (ionizing radiation with ultra-soft X-rays or Bucky rays) usually requires 200 to 400 rad (2 to 4 Grays or Gy) every 1 to 3 weeks for up to a total of 6 treatments, followed by a 6-month hiatus.10 SOR C

Systemic Steroids and Immunomodulators

• Oral prednisone may be used to treat the most severe and recalcitrant case of hand dermatitis. Pulse dosing of 40 to 60 mg daily for 3 to 4 days may be valuable.10 For atopic dermatitis of the hands, an injection of 40 mg triamcinolone acetonide is another option when topical meds are not fully working. SOR C
• Cyclosporine is a potent immunomodulating agent used to treat severe and recalcitrant cases of atopic dermatitis and hand dermatitis. In a systematic review, cyclosporin consistently decreased the severity of atopic dermatitis. The decrease in disease severity was greater at 2 weeks with dosages greater than or equal to 4 mg/kg. After 6 to 8 weeks the relative effectiveness was 55%.11 For patients with severe functional problems this can be a great relief (Figure 147-8). Unfortunately, relapse rates are high after discontinuation of the cyclosporine.10 SOR B
• Mycophenolate mofetil and methotrexate have been reported to be beneficial in case reports.10 SOR C
• Alitretinoin (9-cis-retinoic acid) is an effective treatment for severe chronic hand eczema.12 SOR B Like all systemic retinoids it is teratogenic and requires careful monitoring. This medication is not yet available in the United States, but is being used in Canada and the United Kingdom.

• See Table 147-1.

Patients with chronic hand dermatitis are often desperately looking for help and often appreciate frequent follow-up until the dermatitis is controlled. Patch testing requires three visits within a 1-week period.

Patient Resources

• DermNet New Zealand—http://www.dermnetnz.org/dermatitis/hand-dermatitis.html.

Provider Resources

• Dyshidrotic eczema—http://emedicine.medscape.com/article/1122527.
• Vesicular Palmoplantar Eczema—http://emedicine.medscape.com/article/1124613.

A 2-year-old Hispanic male presents to the clinic with erythematous, round, moist, crusted lesions on the left thigh (Figure 148-1) and right arm. His mother noted several small bumps initially, which developed into coin-shaped lesions over the next few weeks. The child is scratching them but is otherwise healthy. A KOH preparation of the scraping from the lesions did not show fungal structures. The child responds well to treatment with topical midpotency corticosteroids, emollients, and dressing in long-sleeve clothes to prevent scratching the lesions. His nummular eczema resolved in 6 weeks.

Nummular eczema (NE) is a type of eczema characterized by circular or oval-shaped scaling plaques with well-defined borders. The term nummular refers to the shape of a coin (Latin for coin is nummus). The lesions are typically multiple and most commonly found on the dorsa of the hands, arms, and legs. It often overlaps with other clinical types of eczema: atopic dermatitis, stasis dermatitis, and asteatotic eczema.1,2

Nummular dermatitis, discoid eczema, microbial eczema, and orbicular eczema.

• Prevalence is reported to range widely from 0.1% to 9.1%.1
• It is slightly more common in males than in females.1
• Males are also affected at a later age (peak older than age 50 years) than females (peak younger than age 30 years).1
• It is less common in children.

Many factors have been reported in association with NE but their role in the etiology and pathogenesis is not well established:

• NE has been viewed as microbial in origin, either secondary to bacterial colonization or hematogenous spread of bacterial toxins,1,3 but an infectious source is not identified in most cases of NE.
• NE is reported to be associated with xerosis of the skin that subsequently weakens the skin barrier function and sensitizes it to environmental allergens.4
• NE is frequently reported in association with contact sensitization to various agents, including nickel, chromate, balsam of Peru, and fragrances. Allergic or chronic contact dermatitis has been frequently reported to manifest as NE on the dorsa of the hands.1,5
• Onset of NE has been reported in association with various medications, including interferon and ribavirin therapy for hepatitis C6,7 and isotretinoin.8 Most of these reports are based on single or limited number of cases.
• Mercury in the dental amalgam was reported to induce NE in two cases with relapsing NE.9

History

• Onset is reported to be within days to week. Simultaneous or subsequent development of multiple lesions is often reported.
• Intense pruritus or burning is common.
• Lesions may last months to years without treatment and may be recurrent.
• History of medications, atopy, and exposure to allergens may be helpful to tailor the management of NE.

Physical Examination

• Primary morphology includes small papules and vesicles that coalesce to form circular to oval shape patches and plaques (Figures 148-2 and 148-3).
• Secondary morphology includes abrasion and excoriations from scratching (Figure 148-1), weeping and crusting after the vesicles leak (Figures 148-2, 148-3, and 148-4), and scaling and lichenification in more chronic lesions (Figures 148-5 and 148-6). Excessive weeping and crusting may indicate secondary bacterial infection.

Typical Distribution

• Dorsal hand is most commonly affected (Figures 148-2 and 148-7). The extensor aspects of the forearm (Figures 148-3 and 148-6) and the lower leg (Figure 148-5), the thighs (Figure 148-1), and the flanks are frequently involved, but NE may be seen in any part of the body (Figures 148-4, 148-8, and 148-9).

Laboratory Testing

• Diagnosis in most cases is made from clinical features.
• KOH preparation is helpful to investigate for tinea corporis.
• Patch testing may be considered if contact allergy is suspected.

Biopsy

• Biopsy is rarely needed, but should be performed if there is suspicion of other serious clinical entities (e.g., mycosis fungoides, psoriasis) or if the diagnosis is uncertain.

• Tinea corporis may present as pruritic annular lesions with scales and vesicles. Vesicles are typically at the periphery of the lesion compared to NE, where they are also seen in the center. A positive KOH preparation for hyphae can help with the diagnosis (see Chapter 138, Tinea Corporis).
• Psoriasis typically presents with thickened plaques on the extensor surfaces of arms and legs, scalp and sacral areas. Nail changes may be present (see Chapter 152, Psoriasis).
• Lichen simplex chronicus usually presents as a single plaque in an area easily accessible to scratching such as the ankle, wrist, and neck (see Chapter 149, Self-Inflicted Dermatoses).
• Mycosis fungoides is a type of cutaneous T-cell lymphoma, which may present with scaly patches or plaques that are often pruritic and usually erythematous. A biopsy can help make the diagnosis (see Chapter 176, Mycosis Fungoides).
• Nummular lesions of atopic dermatitis may have features similar to NE. Presence of other lesions typically on flexural surfaces, and a history of atopy, asthma, or seasonal allergies may help make the diagnosis (see Chapter 145, Atopic Dermatitis).
• Contact dermatitis (CD) may present with nummular lesions. History of exposure to contact allergens at the affected areas can raise the suspicion for CD. Patch testing may be used to confirm the clinical suspicion (see Chapter 146, Contact Dermatitis).
• Asteatotic dermatitis may have overlapping features with NE but has a less-well-defined margin.

• Emollients are beneficial to help restore and maintain normal skin barrier function. SOR C
• Hydration by bathing before bedtime followed by ointment application to wet skin is reported as an effective method of skin care in patients with eczema.10 SOR B
• A medium- to high-potency topical corticosteroid ointment is the first line of treatment. A cream preparation may be used if patient compliance is a concern with ointments. SOR C
• Topical calcineurin inhibitors such as topical tacrolimus and pimecrolimus have the benefit of not causing skin atrophy and have been shown to be effective in many types of eczema.1 SOR B They have a higher cost compared to topical corticosteroids and have a black box warning because of a reported risk of malignancies.
• Short courses of systemic corticosteroids may be necessary in severe or acute cases. SOR C
• Methotrexate is reported to be safe, effective, and well-tolerated in treatment of moderate to severe childhood NE.11 This was reported in a case series of 25 pediatric patients with refractory NE treated with 5 or 10 mg of methotrexate per week. Sixty-four percent had total clearance after an average of 10.5 months. No serious adverse events were observed in this study.11 SOR B
• Phototherapy may be used in generalized, severe, or refractory cases.1,2 Narrow-band UVB is commonly used and psoralen UVA has been used in more severe cases.2 SOR C
• Topical and oral antihistamines are often needed to treat pruritus. Topical doxepin is reported to be effective in treatment of pruritus associated with eczematous conditions and has a favorable safety profile.12 SOR B
• Topical and systemic antibiotics may be needed to treat secondary or associated bacterial infection. SOR C
• Complementary therapy with probiotics is not effective in treatment of eczema and carries a small risk of adverse events.13 SOR A

Regular follow-up is needed for the patient with chronic, refractory, or relapsing nummular dermatitis until remission or resolution is achieved.

Hydration and protection of skin form irritants is important. Apply moisturizer or topical medications immediately after bathing while the skin is still moist. Avoid strong soaps and use mild fragrance-free soap, or soap alternatives. Avoid tight clothing and fabrics that irritate the skin.

Patient Resources

• American Academy of Dermatology. Nummular Dermatitis—http://www.aad.org/skin-conditions/dermatology-a-to-z/nummular-dermatitis.
• British Association of Dermatologists. Discoid Eczema—http://www.bad.org.uk/site/811/Default.aspx.

Provider Resource

• Medscape. Nummular Dermatitis—http://emedicine.medscape.com/article/1123605.

A 55-year-old woman presents with severe itching on her arms and legs. The itching disrupts her sleep and she sometimes scratches her arms and legs until exhaustion (Figures 149-1 and 149-2).1 She had used moisturizers, emollients, and topical corticosteroids, but they only alleviated the itching temporarily. The itching began 10 months earlier after finalizing the divorce from her husband of 20 years. The patient's right leg had been amputated above the knee after a car accident, and she now wore a prosthetic leg. The patient readily admitted to a great deal of psychological distress. She described feeling depressed since her divorce, and the loss of her leg further aggravated her situation. She has had difficulty securing a job and had high anxiety about being able to pay for rent and bills. The diagnosis made was neurotic excoriations (neurodermatitis) and the patient understood that she was doing this to her own skin. The patient improved with nail cutting, acknowledging the self-inflicted nature of her excoriations and topical clobetasol. One year later, the patient was working in the hospital laboratory with a tremendous improvement in her skin condition (Figure 149-3).

The self-inflicted dermatoses (sometimes referred to as psychogenic dermatoses) include neurotic excoriations, lichen simplex chronicus, and prurigo nodularis. These conditions are caused by pruritus for which no medical cause is apparent, which initiates an itch-scratch cycle. The self-inflicted dermatoses can present a challenge to the clinician, as multiple underlying medical etiologies must be ruled out to arrive at their diagnosis and the pathophysiology of these diseases is not well understood. In addition, they may be difficult to treat successfully. There is no clear standard of care for treatment, although a vast array of treatments targeting different etiologies has been tried clinically, and many have some amount of research to support them. As with other psychosomatic conditions, non-pharmacologic interventions, including the physician-patient relationship itself, can be important to treatment.

• Neurotic excoriations—Neurodermatitis.
• Lichen simplex chronicus—Neurodermatitis circumscripta.
• Prurigo nodularis—Picker's nodules; lichen simplex chronicus, prurigo nodularis type; atypical nodular form of neurodermatitis circumscripta.

• Studies show that neurotic excoriations primarily affect females, with a mean onset between the ages of 30 and 45 years1 (Figures 149-1, 149-2, 149-3, 149-4, and 149-5).
• Neurotic excoriations are present in 2% of patients seen in dermatologic clinics.1
• Lichen simplex chronicus (LSC) is observed more commonly in females than in males (Figures 149-6, 149-7, 149-8, and 149-9). Lichen nuchae is a form of lichen simplex that occurs on the midposterior neck (Figures 149-8 and 149-9).
• LSC occurs mostly in mid-to-late adulthood, with highest prevalence in persons ages 30 to 50 years.2
• For prurigo nodularis (PN) there is no documented difference in frequency between males and females. PN most often occurs in middle-aged and older persons3 (Figures 149-10, 149-11, 149-12, 149-13, 149-14, and 149-15).

• All 3 conditions are found on the skin in regions accessible to scratching.
• Pruritus provokes scratching that produces clinical lesions.
• The underlying pathophysiology is unknown for all 3 conditions. Central nervous system (CNS)4 and peripheral nervous system5-7 dysfunction have been implicated in the pathogenesis of the pruritus underlying the self-inflicted dermatoses.
• Some skin types are more prone to lichenification, such as skin that tends toward eczematous conditions (i.e., atopic dermatitis).2
• One study showed an association between LSC and a certain genotype (short/short) at the serotonin transporter gene-linked polymorphic region.8
• Neurotic excoriations (neurodermatitis) is a result of a psychodermatologic disorder in which patients inflict excoriations and ulcers on their skin and admit to their involvement.
• The pathogenesis of PN is still unknown. PN shares some histologic features (epidermal proliferation) with psoriasis and ichthyosis but is largely self-inflicted.3 There is some evidence to suggest immune dysregulation is involved, as PN is more common in patients with HIV/AIDS and other forms of immunosuppression than in the general population.9

Clinical Features

Itching is the common historical theme for all three self-inflicted dermatoses.

Common psychiatric problems associated with all self-inflicted dermatoses include significant social stress, depression, anxiety, and obsessive-compulsive disorder.

Patients are often observed scratching and rubbing their skin. This results in:

• Lichenification of the skin (skin thickening with exaggerated skin lines) (Figures 149-6 and 149-9).
• Pigmentary changes (especially hyperpigmentation) (Figures 149-4, 149-5, 149-9, 149-11, and 149-15).
• Excoriations, erosions, and ulcerations.

Common physical examination findings for all three disorders include:

• Neurotic excoriations—May vary from dug-out erosions, to ulcers covered with crusts and surrounded by erythema to areas receding into hypopigmented depressed scars (Figure 149-5).
• LSC—One or more slightly erythematous, scaly, well-demarcated, lichenified, firm, rough plaques2 (Figures 149-6, 149-7, 149-8, and 149-9).
• Prurigo nodularis—Raised nodules from 2 to 20 mm, colors vary from shades of red to brown (Figures 149-10, 149-11, 149-12, 149-13, 149-14, and 149-15).

Excoriations are almost always present on initial presentation. With treatment the excoriations may subside and the nodules may remain.

Typical Distribution

• Neurotic excoriations occur on areas easily reached by the patient, such as the arms, legs, and upper back (Figures 149-1, 149-2, 149-3, 149-4, and 149-5).
• LSC occurs on:
  • Hands, wrists, extensor forearms, and elbows (Figure 149-6).
  • Knees, lower legs, and ankles (Figure 149-7).
  • Nape of neck (Figures 149-8 and 149-9).
  • Vulva and scrotum.
• In PN, nodules occur on the extensor surfaces of the arms, the legs, and sometimes the trunk (Figures 149-10, 149-11, 149-12, 149-13, 149-14, and 149-15).

Laboratory Studies

Punch biopsy may be helpful when the diagnosis is uncertain.

• Acne keloidalis nuchae—Acneiform eruption at the hairline from ingrown hairs, worse with shaving and short haircuts (see Chapter 114, Pseudofolliculitis and Acne Keloidalis Nuchae).
• Atopic dermatitis—An allergic skin disorder in patients with a personal or family history of atopic conditions. Patients with atopic dermatitis are more likely to get LSC (see Chapter 145, Atopic Dermatitis).
• Contact dermatitis—A common inflammatory skin condition characterized by erythematous and pruritic skin lesions resulting from the contact of skin with a foreign substance (see Chapter 146, Contact Dermatitis).
• Delusions of parasitosis—Delusions that tiny bugs or parasites are living on or below the patient's skin leading them to try to dig them out with their nails and fingers. This condition looks just like neurotic excoriations; however, the patient believes there are parasites causing the pruritus and it is very difficult to convince them otherwise.
• Nummular eczema—Eczematous lesions in the shape of coins seen most often on the legs.
• Scabies—Look for burrows between the fingers and the typical distribution of scabies on the hands, feet, wrists, waist, and axillae to differentiate scabies from a self-inflicted dermatosis. If you do a scraping and find evidence of the scabies mite that is the best way to confirm a true scabies infestation. Often family members have itching and lesions as well when the real diagnosis is scabies (see Chapter 143, Scabies).

For all 3 self-inflicted dermatoses there is little evidence to guide therapy. The following 3 treatments can be used in all 3 conditions and are based on expert opinion and a few small studies: SOR C

• Topical corticosteroids—Use mid-potency to high-potency steroids except in areas of thin skin.
• Oral antihistamines—Sedating H1 blockers and consider doxepin (start with 10 to 25 mg PO qhs and titrate to response) for refractory cases.
• Oral antibiotics, if secondary infection is present.
• One small study of 3 patients with inflammatory skin diseases and severe nocturnal pruritus who underwent treatment with mirtazapine (Remeron) suggests that this may be an effective alternative for the treatment of nocturnal pruritus.10 SOR C

Get a good psychosocial history and offer the patient treatment for any problems uncovered. It may help for patients to understand the connection between their self-inflicted lesions and their stressors. Some patients will have anxiety disorders or depression, whereas others will be suffering with great psychosocial stressors like loss of work, homelessness, or grief. Offer pharmacotherapy (including selective serotonin reuptake inhibitors [SSRIs]) and counseling if indicated. Refer as needed for these therapies.

Other specific treatments to consider are as follows:

• LSC
  • Doxepin 5% cream has been studied in patients with LSC, nummular eczema, and contact dermatitis. Applied 4 times per day for a period of 7 days led to an 84% response rate in reduction of pruritus (not lesions).11 SOR B
  • Tacrolimus 0.1% ointment applied twice daily for approximately 2 months, then once daily for an additional 3 months was effective in achieving remission from LSC in 1 case report.12
  • In one study of 22 patients with LSC, transcutaneous electrical nerve stimulation (TENS) reduced pruritus by greater than more than 50% in 80% of the patients.5
• Prurigo nodularis—A difficult condition to treat with mild-to-moderate success at best. Here are some treatments to consider:
  • Intralesional steroids—Triamcinolone 5 to 10 mg/cc. SOR C
  • Cryotherapy—Applied to each nodule to flatten the nodules and decrease pruritus. SOR C
  • Calcipotriol—After 8 weeks of calcipotriol treatment, the reduction in the number and size of nodules was 49% and 56%, respectively, compared with 18% and 25% for the betamethasone valerate.13 SOR B
  • UV light (narrow-band UVB) is sometimes useful when the condition is widespread. SOR C
  • Monochromatic excimer light (308 nm) showed partial or complete remission from PN in 9 (81%) of 11 patients.14 SOR C
  • Oral dapsone has been tried with some reported success in this difficult condition. SOR C

Gabapentin has some reported success in reducing pruritus in patients with PN and LSC.6 One case series of oral cyclosporine showed some benefit for PN.15

In AIDS patients with PN, maintaining a CD4+ count over 50 may improve pruritus.9

Help patients to understand that they are unintentionally hurting their own skin. Patients need to minimize touching, scratching, and rubbing affected areas. Suggest that patients gently apply their medication or a moisturizer instead of scratching the pruritic areas. Give patients hope and show them Figures 149-1, 149-2, and 149-3 to demonstrate that even the most severe cases can heal if they stop manipulating their skin.

Follow-up is essential because these problems are chronic and difficult to treat. Patients need to know that you will not abandon them and will continue to work with them to get relief. This is especially important when the patient is suffering from anxiety, depression, or other psychological problems.

Patient Resources

• LSC—http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001875/.
• PN—http://www.aocd.org/skin/dermatologic_diseases/prurigo_nodularis.html.
• Neurotic Excoriations—http://www.aafp.org/afp/2001/1215/p1981.html.

Provider Resources

• LSC—http://emedicine.medscape.com/article/1123423.
• PN—http://emedicine.medscape.com/article/1088032.
• Neurotic Excoriations—http://emedicine.medscape.com/article/1122042.

A 26-year-old man was given trimethoprim-sulfamethoxazole for sinusitis and broke out in hives 1 week later. The hives were all over his trunk and arms (Figures 150-1 and 150-2). He had no airway compromise and had only urticaria without angioedema. His sinus symptoms were mostly resolved, so he was told to stop the antibiotic and take an oral antihistamine. The H1-blocker gave him relief of symptoms and the wheals disappeared over the next 2 days.

Urticaria and angioedema are a heterogeneous group of diseases that cause swelling of the skin and other soft tissues. They both result from a large variety of underlying causes, are elicited by a great diversity of factors, and present clinically in a highly variable way.1 Standard hives with transient wheals is the most common manifestation of urticaria.

Hives.

• It is estimated that 15% to 25% of the population may have urticaria sometime during their lifetime.2
• Urticaria affects 6% to 7% of preschool children and 17% of children with atopic dermatitis.2
• Among all age groups, approximately 50% have both urticaria and angioedema, 40% have isolated urticaria, and 10% have angioedema alone.2
• Acute urticaria is defined as less than 6 weeks' duration. A specific cause is more likely to be identified in acute urticaria.2
• The cause of chronic urticaria (>6 weeks' duration) is determined in less than 20% of cases.2
• Chronic urticaria is twice as common in women as in men.3
• Chronic urticaria predominantly affects adults.3
• Up to 40% of patients with chronic urticaria of more than 6 months' duration still have urticaria 10 years later.3

• The pathophysiology of angioedema and urticaria can be immunoglobulin (Ig) E mediated, complement mediated, related to physical stimuli, autoantibody mediated, or idiopathic.
• These mechanisms lead to mast cell degranulation resulting in the release of histamine. The histamine and other inflammatory mediators produce the wheals, edema, and pruritus.
• Urticaria is a dynamic process in which new wheals evolve as old ones resolve. These wheals result from localized capillary vasodilation, followed by transudation of protein-rich fluid into the surrounding skin. The wheals resolve when the fluid is slowly reabsorbed.
• Angioedema is an edematous area that involves transudation of fluid into the dermis and subcutaneous tissue (Figures 150-3 and 150-4).

The following etiologic types exist:

• Immunologic—IgE mediated, complement mediated. Occurs more often in patients with an atopic background. Antigens are most commonly foods or medications. The most common foods are milk, nuts, wheat, and shellfish.
• Physical urticaria—Dermatographism, cold, cholinergic, solar, pressure, vibratory urticaria (Figures 150-5 and 150-6).
• Urticaria caused by mast cell-releasing agents—Mastocytosis, urticaria pigmentosa (Figures 150-7 and 150-8).
• Urticaria associated with vascular/connective tissue autoimmune disease.
• Hereditary angioedema is a potentially life-threatening disorder that is inherited in an autosomal dominant manner. In this disease, angioedema occurs without urticaria (Figure 150-9).

Clinical Features

• Symptoms include itching, burning, and stinging.
• Wheals vary in size from small, 2-mm papules of cholinergic urticaria (Figure 150-6) to giant hives where a single wheal may cover a large portion of the trunk.
• The wheal may be all red or white, or the border may be red with the remainder of the surface white.
• Wheals may be annular (Figures 150-10 and 150-11).
• If dermatographism is present, one can write on the skin and be able to see the resulting words or shapes (Figure 150-5).
• If you suspect urticaria pigmentosa, stroke a lesion with the wooden end of a cotton-tipped applicator. This induces erythema of the plaque and the wheal is confined to the stroke site. This is called Darier sign (Figure 150-12).

Typical Distribution

• Angioedema is seen more often on the face and is especially found around the mouth and eyes (Figures 150-3 and 150-4). Sometimes angioedema can occur on the genitals or the trunk (Figure 150-13).
• Urticaria can be found anywhere on the body and is often on the trunk and extremities (Figures 150-1 and 150-2).

Laboratory Studies

Consider tests that might help reveal the cause of the urticaria and/or angioedema.

• Order complement studies to investigate for hereditary or acquired C1 esterase inhibitor deficiency when angioedema occurs repeatedly without urticaria (Figure 150-9).
• Consider allergen skin testing and/or in vitro tests for when the history reveals that urticaria/angioedema occurs after direct contact with a suspected allergen.
• Punch biopsy of the involved area may be used to diagnose urticarial vasculitis or mastocytosis.

• Insect bites—A good history and physical examination should help to distinguish between insect bites and urticaria.
• Erythema multiforme like urticaria can occur in response to an allergic/immunologic reaction to medications, infections, and neoplasms. The classic lesion of erythema multiforme is the target lesion in which there is disruption of the epithelium in the center. This disruption may be a vesicle, bulla, or erosion. Do not confuse annular lesions or concentric rings with erythema multiforme if the epidermis is intact (Figure 150-11 is not erythema multiforme) (see Chapter 177, Erythema Multiforme, Stevens-Johnson Syndrome, and Toxic Epidermal Necrolysis).
• Urticarial vasculitis typically has lesions that last longer than 24 hours. The lesions are found more commonly on the lower extremities, and when they heal, they often leave hyperpigmented areas. Causes range from a hypersensitivity vasculitis, such as Henoch-Schönlein purpura, to underlying connective tissue disease (Figure 150-14).2
• Mast cell releasability syndromes are syndromes in which there are too many mast cells in the skin or other organs of the body. These include cutaneous mastocytosis and urticaria pigmentosa (Figures 150-7, 150-8, and 150-12).
• Pruritic urticarial papules and plaques of pregnancy can be differentiated from urticaria in pregnancy because the eruption remains fixed and increases in intensity until delivery (Figure 150-15) (see Chapter 75, Pruritic Urticarial Papules and Plaques of Pregnancy).
• Pemphigoid gestationis can have lesions that are urticarial. However, it also has bullae that distinguish it from urticaria and of course the patient is pregnant or postpartum (see Chapter 76, Pemphigoid Gestationis).

Nonpharmacologic Therapy

• Avoid any causative agent, medication, stimulus, or antigen if found. SOR B
• Angiotensin-converting enzyme inhibitors (ACEIs) are especially prone to causing angioedema so should be stopped as soon as possible when suspected to be causative of angioedema or urticaria (Figure 150-3).1 SOR A Even an angiotensin receptor blocker (ARB) can cause angioedema and should be suspected in a patient on this class of medication (Figure 150-16).
• In chronic urticaria, patients may benefit from avoidance of potential urticarial precipitants such as aspirin, NSAIDs (Figure 150-17), opiates, and alcohol.1 SOR B
• Infections may be a cause, an aggravating factor, or an unassociated bystander.1 Look for sources of chronic infections such as parasitic infections, dental infections, GI infections, respiratory infections, and tinea pedis. Treat these, as it is possible, but unproven, that they can contribute to the chronic urticaria. SOR C
• Stop all unnecessary nonprescription medications, supplements, and vitamins in chronic urticaria. SOR C
• Avoidance of physical stimuli for the treatment of physical urticaria is desirable, but not always possible (observational studies only).1 SOR B
• Stress reduction techniques may help in chronic urticaria but this is unproven. SOR C

Antihistamines

• Low-sedating, second-generation antihistamines should be prescribed as a first-line treatment for chronic urticaria.4-6 SOR A
• Increasing the dose of cetirizine from 10 mg to 20 mg daily produced a significant improvement in the severity of wheal and itching in urticaria refractory to the standard doses of antihistamines.7 SOR B
• The British guidelines even suggest using antihistamines at up to quadruple the manufacturers' recommended dosages before changing to an alternative therapy. They also recommend waiting up to 4 weeks to allow full effectiveness of the antihistamines before considering referral to a specialist.1 SOR C
• All patients should be offered the choice of at least two low-sedating H1 antagonists because responses and tolerance vary between individuals.8 SOR A
• Addition of a sedating antihistamine at night may help patients sleep better, although they probably add little to existing H1 receptor blockade.8
• The addition of an H2 antagonist may give better control of urticaria than H1 antagonists alone, SOR B although a benefit is not always seen.8 In one study, adding H2 blockers to H1 antagonists resulted in improvement of certain cutaneous outcomes for patients presenting with acute allergic syndromes to an emergency department.9 SOR B
• When initial antihistamines are not working, consider doxepin, an antidepressant and potent H1 antagonist.10 SOR B Its use is limited by the side effects of sedation and dry mouth. Start with 10 mg doxepin in the evening and titrate up as needed and tolerated.
• Low-sedating antihistamines seem to be effective in the treatment of acquired cold urticaria by significantly reducing the presence of wheals and pruritus after cold exposure.11 SOR A

Corticosteroids

• Oral corticosteroids should be restricted to short courses for severe acute urticaria or angioedema affecting the mouth (e.g., prednisone 60 mg/day for 3 to 4 days in adults).8,12 SOR B
• Short tapering courses of oral steroids over 3 to 4 weeks may be necessary for urticarial vasculitis and severe delayed pressure urticaria.
• Long-term oral corticosteroids should not be used in chronic urticaria. It is better to use oral cyclosporine if needed as it has a far better risk-to-benefit ratio compared with steroids.1,8
• A randomized controlled trial showed that clobetasol 0.05% in a foam formulation was safe and effective in the short-term treatment of patients with delayed pressure urticaria.13 SOR B

Immunomodulatory Agents

• Immunosuppressive therapies for autoimmune urticaria should be restricted to patients with disabling disease who have not responded to optimal conventional treatments.6
• A retrospective study of methotrexate in 8 patients with recalcitrant chronic urticaria indicated that methotrexate was both safe and effective, with a mean dose of 15 mg methotrexate/week. Seven of 8 patients achieved a complete response and 5 of 8 remained disease-free after methotrexate was stopped.14 SOR B
• Cyclosporine, plasmapheresis, anti-IgE (Omalizumab), and intravenous immunoglobulin have been used in severe recalcitrant cases.1 SOR C
• Plasmapheresis is very costly and should be reserved for autoantibody-positive chronic spontaneous urticaria patients.1

Others

• Epinephrine is valuable in severe acute urticaria or angioedema, especially if there is a suspicion of airway compromise or anaphylaxis.
• The evidence for leukotriene modifiers in the treatment of urticaria is poor. SOR C
• Ecallantide is a new plasma kallikrein inhibitor for the subcutaneous treatment of acute attacks of hereditary angioedema.15 SOR B
• Antiinflammatory drugs, such as colchicine, dapsone and sulfasalazine, have been reported as helpful in uncontrolled trials or case series.1

In most cases, we are not able to find the cause of urticaria. This is especially true for chronic urticaria. Fortunately, most chronic urticaria will subside over time and there are medicines to treat the condition until it runs its course. If one medication doesn't work keep your follow-up visits to try other medications. Carefully observe for causative agents.

Follow-up is especially needed when the urticaria/angioedema persist or recur.

Patient Resources

• eMedicineHealth.com is a consumer health site with information and support groups—http://www.emedicinehealth.com/hives_and_angioedema/article_em.htm.

Provider Resources

• Well written guideline based upon a joint initiative of a number of European dermatology, allergy, and immunology organizations—http://onlinelibrary.wiley.com/doi/10.1111/j.1398-9995.2009.02178.x/full.