White : Diseases of the Skin - Urticaria and Pruritus

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Gary M. White & Neil H. Cox

Diseases of the Skin

9	Urticaria and Pruritus

PRUITUS AND RELATED DISORDERS

Generalized pruritus without skin changes

Etiology and pathogenesis

Some patients present with itching and very little rash. A variety of causes may be found (Table 9.5).

Clinical

To reach this diagnosis, a careful complete skin examination must be performed. Dry skin (xerosis) is a common cause of pruritus, especially in the elderly in the winter. Look for fine scale and accentuated skin lines, especially on the legs. Are there any signs of scabies (e.g. classic burrows in the web spaces)? Any new medications? Any new topical medications or exposures? Make sure to test for dermatographism.

Localized pruritus is a rather different issue: it may occur on the back (notalgia paresthetica) or arm (brachioradial pruritus), as discussed later. However, even localized itch may rarely be a manifestation of internal malignancy (e.g. severe nasal tip itch due to tumor of the fourth ventricle).

Differential diagnosis

If the patient is found to truly have pruritus without any skin changes, internal causes must be considered, including cholestasis, iron deficiency (even without anemia), rapid weight loss, renal disease, hypothyroidism, polycythemia rubra vera, and Hodgkin lymphoma. Delusions of parasitosis should be excluded, and depressive illness should always be considered; even if not the whole cause, it may aggravate the degree of symptoms.

An appropriate work-up includes a history and physical examination with special emphasis on lymph nodes, plus CBC, serum bilirubin, alkaline phosphatase, antimitochondrial antibody, ferritin, thyroid function tests, creatinine, blood urea nitrogen (BUN), and chest x-ray. Screening for HIV may be appropriate. An interesting report found 39% of patients with unexplained itching to have evidence of hepatitis C infection.

Treatment

Treatment should be tailored to the cause. If no cause is found, a medium- to high-potency topical steroid applied after the shower to the itchiest areas, an emollient cream or ointment applied elsewhere, and a sedating antihistamine at nighttime may be tried. If this fails, doxepin before sleeping or UVB may be tried. Low-dose prednisone is occasionally helpful. HIV-associated pruritus can be treated effectively with UVB. Ondansetron (initially 8mg/day, then tapered as possible), a competitive and selective antagonist of serotonin receptors, has relieved itching in a variety of situations (e.g. pruritus associated with cholestatic jaundice or chronic renal insufficiency).

Fig 9.11 Notalgia paresthetica. ( a ) This middle-aged man was plagued by a very pruritic fixed area on his left back, outlined here in pen. As a cruel quirk of fate, this itch is often hard to scratch. (b) Note the prominent hyperpigmentation resulting from chronic scratching and rubbing in this patient with bilateral symptoms.

Notalgia paresthetica

Etiology and pathogenesis

Patients with notalgia paresthetica experience persistent itching in a fixed area in the middle of the back. Notalgia paresthetica is thought to represent a sensory neuropathy, as the cutaneous nerves take a right angle in their course to innervate that location. In one study, the striking correlation of notalgia paresthetica localization with radiographic degenerative changes in the spine suggests that spinal nerve impingement may contribute to the pathogenesis of this entity. In another report, a patient developed notalgia paresthetica of the right upper back and shoulder caused by a large osteophyte in the C3–C4 intervertebral space, impinging on the right C4 nerve root (visualized by magnetic resonance imaging).

Clinical

Middle-aged to elderly patients may present with a very pruritic, fixed spot on the back, just to one side of the midline (Fig.9.11). Hyperpigmentation may be present, and in most patients is thought to be secondary to chronic scratching. Macular amyloidosis may be the cause of the hyperpigmentation in some cases.

Differential diagnosis

Idiopathic macular amyloid may be considered but typically involves the upper back. Generally, there is no meaningful differential: it is simply a matter of whether the physician has ever heard of this entity.

Treatment

Most of the time, the benefit of heroic interventions is not worth the effort. (The patient may merely be told to get a back scratcher.) Still, if therapy is desired, the following may be tried. Capsaicin applied topically 3–5 times/day for 2 months has been reported to decrease the pruritus. A eutectic mixture of local anesthetic (2.5% lidocaine, 2.5% prilocaine), applied twice a day with occlusion, has also been reported to be effective. In the case of the nerve impingement described earlier, cervical epidural steroid injection resulted in near-complete resolution of the symptoms. In another case, paravertebral block at D5–D6, and later at D3–D4, with 5mL of bupivacaine (0.75%) combined with 40mg of methylprednisolone acetate relieved all symptoms for 12 months.

Fig 9.12 Brachioradial pruritus. This man had such chronic pruritus on the one arm that he could not resist scratching. Multiple excoriations and old white scars are shown

Brachioradial pruritus

Etiology and pathogenesis

Patients with brachioradial pruritus experience chronic and persistent itching along the extensor forearm. There is ongoing debate regarding the etiology: it has long been viewed as a photodermatosis, but many authors feel that it represents a radiculopathy or some form of nerve entrapment.

The visible light spectrum was implicated in one report, and, because antihistamines helped in that case, it was suggested that some patients may experience degranulation of mast cells from visible light. Most cases do not fit one specific nerve distribution and radiographs are usually normal, which casts some doubt on the radiculopathy theory. Conversely, involvement of the non-driver's side forearm, or occurrence in those with minimal sunlight exposure, casts doubt on the idea of a photodermatosis, and several case series have documented features supporting a neuropathic component. Additionally, dramatic response to capsaicin in some cases is more supportive of this being a neuropathic process.

Clinical

Pruritus along the extensor forearm on one side is characteristic (Fig.9.12). It may be worse in the summer with sunlight exposure. The classic patient is a professional driver whose arm hangs out the window while driving (a feature that might cause either solar exposure or neuropathy!), but any adult may be affected.

Differential diagnosis

As with nostalgia paresthetica, there is no meaningful differential if the physician has ever heard of this entity.

Treatment

Long-sleeved shirts to shield the arm from the sun may completely clear the symptoms (e.g. in 6 weeks). A medium- to high-potency topical steroid may be tried. In one report, cetirizine completely controlled a patient's symptoms. Topical capsaicin or oral gabapentin 300 mg t.i.d. has also produced marked benefit in various patients. Cervical spine radiology may be considered to rule out a radiculopathy.

PRACTICE POINTS

•	Patients with generalized itch but no rash may have an internal cause; however, previously unappreciated dry skin, mild dermatographism, and subtle rashes are all more common than systemic causes of pruritus.
•	Beware of interpreting scratch marks as a primary rash. Look at the central upper back to see if it is spared (the butterfly sign).
•	Localized itch without rash typically occurs on the mid-back (notalgia paresthetica) or the dorsal forearm (brachioradial pruritus); both are underdiagnosed conditions.
•	Even in those with minimal rash (especially the elderly), and especially in patients with nondescript scattered rash, always consider scabies as a cause of pruritus.

Itchy red bump disease

Etiology and pathogenesis

The diagnosis of itchy red bump disease is one of exclusion of the differential diagnoses described here. If no specific cause is found, the term itchy red bump disease may be used. It is unclear whether this is a specific entity, as no cause has been identified. Most patients are male and elderly.

Clinical

An adult with chronic pruritus and 1–2-mm erythematous papulovesicles scattered on the body is characteristic (Fig. 9.13).

Fig 9.13 ( a , b ) Itchy red bump disease. These tiny red bumps of the trunk are very itchy. Often, their cause is unknown.

Differential diagnosis

The patient with multiple itchy red bumps should have a careful drug history taken; should be carefully examined to exclude scabies; and should have patch testing, skin biopsy, and a trial of antibiotics. These maneuvers should exclude the most likely differentials of scabies, Grover disease, allergic contact dermatitis, drug rash, dermatitis herpetiformis, and folliculitis. Some patients have been found to have hepatitis B.

Treatment

Potent topical steroids before sleeping should be tried initially. If this fails, PUVA should be given. In one study, PUVA had the best chance of either helping (six out of nine patients) or clearing (three out of nine patients) itchy red bump disease. Antihistamines, UVB, intramuscular triamcinolone, and low-dose prednisone may be tried.

Delusions of parasitosis

Patients with delusions of parasitosis are convinced that some sort of parasite or ‘bug' is living in or on their skin. This is discussed in more detail in Chapter 27.

Lichen simplex chronicus and prurigo nodularis

Etiology and pathogenesis

From an evolutionary standpoint, the occasional scratch is good, as it may dislodge a blood-sucking mosquito or tick, etc. However, chronic, daily, incessant scratching is bad. It damages the skin and exposes deeper tissues to infection. In response, the skin thickens in an attempt to protect itself. The term lichen simplex chronicus (LSC) refers to plaques of skin that have developed in response to repeated scratching, and the term prurigo nodularis refers to nodules.

The initial trigger may be one of the causes of generalized pruritus discussed in this chapter, particularly in those with widespread lesions of prurigo nodularis. Patients with atopic dermatitis may develop lichenification, usually at sites of otherwise obvious eczema but sometimes at distant sites.

In patients with LSC, it is always worth considering an underlying contact allergy, particularly if the vulva is affected or if LSC occurs at a site that is unusual.

Clinical

A chronic, hyperkeratotic, lichenified, excoriated plaque that the patient scratches daily is characteristic (Fig.9.14). Often, the skin lines are accentuated within the lesion. Sometimes the skin is thickened relatively uniformly, in others the appearance has a more cobblestoned morphology: lesions may be relatively sharply defined or may be more diffuse at the margins. LSC may occur virtually anywhere, but common sites include the ankle, shin, scrotum, vulva, and nape and side of the neck. It is often less threatening and more helpful when trying to elicit a history of chronic scratching to ask the patient ‘Does it itch?' rather than asking ‘Do you scratch?'

Fig 9.14 Lichen simplex chronicus (LSC). ( a ) Note the lichenification, excoriations, and accentuation of skin lines that have resulted from repeated scratching. (b) The skin of LSC may take on a lichenoid appearance, as shown here in a lesion on the leg. (c) Fiddler's neck. The chronic pressure and friction of a violin caused this indurated, thickened plaque. (d ) LSC of the scrotum. Note the thickened, fissured skin. An epidermal inclusion cyst is seen in the skin on the right side of the scrotum.

In prurigo nodularis, 5–15-mm hyperkeratotic, verrucous nodules scattered on the extensor surfaces of the arms and legs are characteristic (Fig.9.15). Onset is usually in middle age, and women are more commonly affected. Many patients have a family history of atopy.

Fig 9.15 Prurigo nodularis.(a) Multiple hyperkeratotic nodules and plaques on the right leg, caused by daily scratching. (b) Close-up view. (c)Prurigo of the hand. (d) Multiple discrete indurated nodules on the legs. Some have an excoriated surface. In this case, the only causative factor identified was iron deficiency due to previous gastrointestinal bleeding. ( e ) Prurigo nodules showing the nodular lesions and the surface excoriation.

A condition of prurigo nodularis lesions that develop in patients with bullous pemphigoid has been called pemphigoid nodularis.

In any condition where widespread scratching or rubbing occurs in the absence of an overt primary dermatosis, the area of the back where the patient is unable to reach to scratch may be spared (the butterfly sign, Fig. 9.16), but beware of missing the subtle causes of generalized pruritus discussed earlier, for example dermatographism (Fig. 9.17).

Fig 9.16 Some effects of scratching.(a) Linear purpura from scratching. (b) Butterfly sign. The mid- and upper back is relatively inaccessible to the hands. Some patients have a diffuse eruption, except for this area. The appearance has been likened to a butterfly. The implication is that any rash is secondary to scratching, rather than representing a primary dermatosis. Note that, with the use of a back scratcher or other instrument, even this area is accessible.

Fig 9.17 Prurigo nodularis and excoriations.(a) This woman presented with a diffuse pruritic rash that on initial inspection was thought to merely represent excoriations and prurigo nodularis. (b) Closer inspection showed the primary lesions of dermatographism.

Differential diagnosis

Lichen simplex chronicus is usually fairly obvious by its morphology, the most notable differential diagnosis being chronic areas of lichen planus. Psoriasis may be diagnosed, but solitary lesions of psoriasis are uncommon, and LSC has neither the sharp margin nor the hard silvery scale that are typical of psoriasis.

Nodular prurigo is also usually characteristic but may need to be distinguished by biopsy from a range of other conditions, especially lichen planus (especially nodular lesions on the legs), granulomatous disorders, and neoplasms.

Treatment

Don't scratch! This single admonition is often left out by the doctor, leading to treatment failure. Tell the patient, ‘No matter how strong a steroid I give you, this problem will continue if you continue to scratch'. Explore with the patient when they scratch: at night, when nervous, etc. Remember that scratching and rubbing occur at night even if the patient is asleep, and even if daytime itch is controlled.

Many factors may need to be combined for therapeutic success (Table 9.6).

PRACTICE POINTS

•	In lichen simplex and nodular prurigo, remember that scratching and rubbing occur at night even if the patient is asleep, and even if daytime itch is controlled.
•	Contact allergy may cause or complicate vulval lichen simplex chronicus.

If the mid- and upper back is completely spared by an otherwise generalized itch rash (the butterfly sign), then the implication is that the rash is secondary to scratching, rather than representing a primary dermatosis.

Any form of chronic rubbing or excoriation is likely to be difficult to treat and may require the combination of several treatment modalities.

Dermatitis artefacta

Etiology and pathogenesis

The term dermatitis artefacta refers to skin lesions inflicted consciously with the intent of gaining sympathy, avoiding work, collecting insurance, or avoiding responsibility. Absolute proof of the diagnosis may be difficult to obtain.

Clinical

Irregularly shaped, bizarre skin lesions on easily accessible skin including the face (Figs 9.18 and 9.19) and arms (Fig. 9.20) are characteristic. The appearance depends on the mode of creation, which can include caustic substances, injection of foreign material, fingernails, or hot metal. Extensive scarring can result (Fig. 9.21).

Fig 9.18 Dermatitis artefacta.(a) This teenaged girl said she woke up with these large facial lesions and has no idea how they got there. She has had approximately 10 episodes in 1 year and never seems to be very upset about them. (b) Dermatitis artefacta in an elderly woman who lives alone.

Fig 9.19 Acne excoriée.(a) Women often will excoriate their acne to such a degree that the acne is no longer visible. Significant scarring often results.
(b) This patient has a severe case and has caused much scarring.

Fig 9.20 Dermatis artefacta.(a) This patient had injured herself on a thorn bush almost a year prior to the photograph. She was convinced that thorns were still embedded in the skin. Her constant digging prevented the skin from healing. Note the oval and linear pattern. (b) Dermatitis artefacta in a teenaged girl.

Fig 9.21 Scars.(a) This pattern of linear white scars on the upper back is a typical pattern that occurs as a result of years of scratching. (b) Shallow hypopigmented and/or pink circular scars are common on the legs, as shown here. Unfortunately, they are permanent. Acute excoriations are also seen.

Table 9.6 MEASURES THAT MAY BE REQUIRED TO TREAT CHRONIC RUBBING OR SCRATCHING 0. IN LICHEN SIMPLEX CHRONICUS OR NODULAR PRURIGO

Explanation of the role of scratching or rubbing in causation or at least in perpetuation of the lesion.

Short-term high-potency topical steroids are helpful to alleviate the itch. Use until the lesion is flat. Steroid-impregnated tape is helpful for small lesions.Intralesional steroids can be used.

Cover the lesion to prevent damage (e.g. use occlusive bandages for limbs with nodular prurigo), and ensure that the dressings are not removed until they are due to be replaced (remove the window of opportunity to scratch).Many ressings or bandages can be applied in conjunction with the topical steroid applied.

Decrease the potential to cause damage (e.g. cut the fingernails, get the patient to wear gloves).

Give sedating antihistamines, especially at night, or possibly a tricyclic antidepressant (which have both sedating and powerful antihistamine effects as well as their antidepressant function).

Avoid irritants, especially soaps for vulval lichen simplex chronicus (LSC), and replace with emollients.

Have family members encourage compliance.

Consider other topical agents, such as topical doxepin, topical local anesthetics, and topical capsaicin cream (although this was not helpful in LSC in onedouble-blind, placebo-controlled trial in which itching was described as worse at the active drug site).

Consider other options, such as phototherapy for nodular prurigo and excision for localized scrotal LSC.

Hypnosis or psychotherapy are less commonly used but have potential value.

Remember that there may be a systemic cause for itch in nodular prurigo, or a local cause in LSC, and investigate appropriately. For example, lichenification may conceal many primary dermatoses of the vulva, and contact dermatitis (e.g. to fragrances in hygiene wipes) may be either a cause or a secondary factor at this site.

Keep treating: remember that any excoriations noted on follow-up indicate continued scratching by the patient.