CHAPTER 4: PRURITUS AND NEUROCUTANEOUS DERMATOSES

Question 1

Pruritus, commonly known as itching, is a sensation exclusive to the skin. It may be defined as the sensation that produces the desire to scratch. Pruritogenic stimuli are first responded to by ______

Answer 1

keratinocytes, which release a variety of mediators, and fine in raepidermal C-neuron filaments.

Question 2

What are the 4 categories of itch?

Answer 2

Itch has been classified into four primary categories, as follows:

• Pruritoceptive itch, initiated by skin disorders
• Neurogenic itch, generated in the central nervous system and caused by systemic disorders
• Neuropathic itch, caused by anatomic lesions of the central or peripheral nervous system
• Psychogenic itch, the type observed in parasitophobia

An overlap or mixture of these types may be causative in any individual patient.

Question 3

How do you manage itch?

Answer 3

General guidelines for therapy of the itchy patient include keeping cool and avoiding hot baths or showers and wool clothing, which is a nonspec fic irritant, as is xerosis. Many patients note itching increases after showers, when they wash with soap and then dry roughly. Using soap only in the axilla and inguinal area, patting dry and applying a moisturizer can often help prevent such exacerbations. If itching is severe, a trial of “soaking and smearing” may provide significant relief (see winter itch later in this chapter). Patients often use an ice bag or hot water to ease pruritus; however, hot water can irritate the skin, is effective only for short periods, and over time exacerbates the condition.

Relief of pruritus with topical remedies may be achieved with topical anesthetic preparations. Many contain benzocaine, which may produce contact sensitization. Pramoxine in a variety of vehicles, lidocaine 5% ointment, eutectic mixture of lidocaine and prilocaine (EMLA) ointment, and lidocaine gel are preferred anesthetics that may be beneficial in localized conditions EMLA and lidocaine may be toxic if applied to large areas. Topical antihistamines are generally not recommended, although doxepin cream may be effective for mild pruritus when used alone. Doxepin cream may cause contact allergy or a burning sensation, and somnolence may occur when doxepin is used over large areas. Topical lotions that contain menthol or camphor feel cool and improve pruritus. They may be kept in the refrigerator to enhance this soothing effect. Other lotions have specific ceramide content designed to mimic that of the normal epidermal barrier. Capsaicin, by depleting substance P, can be effective, but the burning sensation present during initial use frequently causes patients to discontinue its use. Topical steroids and calcineurin inhibitors effect a decrease in itching through their antiinflammatory action and therefore are of limited efficacy in neurogenic, psychogenic, or systemic disease–related pruritus.

Phototherapy with ultraviolet B (UVB), UVA, and psoralen plus UVA (PUVA) may be useful in a variety of dermatoses and pruritic disorders. Many oral agents are available to treat pruritus. Those most frequently used by nondermatologists are the antihis amines. First-generation H1 antihistamines, such as hydroxyzine and diphenhydramine, may be helpful in nocturnal itching, but their efficacy as antipruritics is disappointing in many disorders, except for urticaria and mastocytosis. Doxepin is an exception in that it can reduce anxiety and depression and is useful in several pruritic disorders. Sedating antihistamines should be prescribed cautiously, especially in elderly patients because of their impaired cognitive ability. The nonsedating antihistamines and H2 blockers are only effective in urticaria and mast cell disease. Opioids are involved in itch induction. In general, activation of µ-opioid receptors stimulates itch, whereas κ-opioid receptor stimulation inhibits itch perception; however, the interaction is complex. Additionally, opioid-altering agents such as naltrexone, naloxone, nalfurafine, and butorphanol have significant side effects and varying modes of delivery (intravenous, intranasal, oral). Initial reports of benefit in one condition are often followed by conflicting reports on further study. Specific recommendations in select pruritic conditions are detailed in those sections. These agents appear most useful for cholestatic pruritus. Central reduction of itch perception may be effected by anticonvulsants, such as gabapentin and pregabalin, and antidepressants, such as mirtazapine and the selective serotonin reuptake inhibi ors (SSRIs). These take 8–12 weeks to attain full onset of action Thalidomide, through a variety of direct neural effects, immunomodulatory actions, and hypnosedative effects, is also useful in select patients.

5
Q
What are some of the internal causes of itching?

A
The most important internal causes of itching include liver disease, especially obstructive and hepatitis C (with or without evidence of jaundice or liver failure) renal failure, diabetes mellitus, hypothyroidism and hyperthyroidism, hematopoietic diseases (e.g., iron deficiency anemia, polycythemia vera), neoplastic diseases (e.g., lymphoma [especially Hodgkin disease and cutaneous T-cell lymphoma], leukemia, myeloma), internal solid-tissue malignancies, intestinal parasites, carcinoid, multiple sclerosis, acquired immunodeficiency syndrome (AIDS), connective tissue disease (particularly dermatomyositis) and neuropsychiatric diseases, especially anorex a nervosa.

The pruritus of Hodgkin disease is usually continuous and at times is accompanied by severe burning. The incidence of pruritus is 10%–30% and is the first symptom of this disease in 7% of patients. Its cause is unknown. The pruritus of leukemia, except for chronic lymphocytic leukemia, has a tendency to be less severe than in Hodgkin disease.

Internal organ cancer may be found in patients with generalized pruritus that is unexplained by skin lesions. However, no significant overall increase of malignant neoplasms can be found in patients with idiopathic pruritus. A suggested workup for chronic, generalized pruritus includes a complete history, thorough physical examination, and laboratory tests, including complete blood count (CBC) and differential; thyroid, liver, and renal panels; fasting blood glucose; hepatitis C serology; human immunodeficiency virus (HIV) antibody (if risk factors are present); urinalysis; stool for occult blood; serum protein electrophoresis; and chest x-ray evaluation. Presence of eosinophilia on the CBC is a good screen for parasitic diseases, but if the patient has been receiving systemic corticosteroids, blood eosinophilia may not be a reliable screen for parasitic diseases, and stool samples for ova and parasites should be submitted. Additional radiologic studies or specialized tests are performed as indicated by the patient’s age, history, and physical findings. A biopsy for direct immunofluorescence is occasionally helpful to detect dermatitis herpetiformis or pemphigoid.

Treatment of the itch associated with some of these internal conditions is discussed later in this chapter or under those specific diseases in other chapters; however, in other conditions listed previously treatment of the underlying disease state (e.g., treating the cancer, replacing thyroid hormone in hypothyroidism) causes relief of the pruritus. Be aware that disease specific therapies can exacerbate itching during treatment, for instance in cancer patients treated with biologic agents such as the anti EGFR monocolonal antibiodies.

Question 4

What are some of the internal causes of itching?

Answer 4

The most important internal causes of itching include liver disease, especially obstructive and hepatitis C (with or without evidence of jaundice or liver failure) renal failure, diabetes mellitus, hypothyroidism and hyperthyroidism, hematopoietic diseases (e.g., iron deficiency anemia, polycythemia vera), neoplastic diseases (e.g., lymphoma [especially Hodgkin disease and cutaneous T-cell lymphoma], leukemia, myeloma), internal solid-tissue malignancies, intestinal parasites, carcinoid, multiple sclerosis, acquired immunodeficiency syndrome (AIDS), connective tissue disease (particularly dermatomyositis) and neuropsychiatric diseases, especially anorex a nervosa.

The pruritus of Hodgkin disease is usually continuous and at times is accompanied by severe burning.

Question 5

What is the most common systemic cause of pruritus?

Fig. 4.2 (A) Acquired perforating dermatosis of uremia.

Answer 5

Chronic kidney disease (CKD)

Question 6

Management of pruritus scondary to CKD?

Answer 6

1. Many patients have concomitant xerosis, and aggressive use of emollients, including “soaking and smearing” (see winter itch later in this chapter), may help.
2. A trial of γ-linolenic acid cream twice daily was effective, as was one using baby oil.
3. Gabapentin given three times weekly at the end of hemodialysis sessions can be effective, but its renal excretion is decreased in CKD, so a low initial dose of 100 mg after each session with slow upward titration is recommended.
4. A mainstay of CKD-associated pruritus has been narrow-band (NB) UVB phototherapy, but a randomized controlled trial (RCT) failed to confirm its efficacy. Broad-band UVB may be best in the CKD patient.
5. Naltrexone, topical tacrolimus, and ondansetron also were reported to be useful in initial trials, but subsequent studies indicated these agents are ineffective.
6. Nalfurafine, 5 µg once daily after supper, has demonstrated improvement and was relatively well tolerated over a 1-year study.
7. Thalidomide, intranasal butorphanol, and intravenous lidocaine are less practical options. Patients on peritoneal dialysis have a lower severity of pruritus than those on hemodialysis.
8. Renal transplantation will eliminate pruritus.

Question 7

What causes biliary pruritus?

Answer 7

Itching of biliary disease is probably caused by central mechanisms.

The pathophysiology is not well understood, but it appears that lysophosphatidic acid, formed by the action of the enzyme autotaxin on lysophosphatidylcholine, is central.

The serum conjugated bile acid levels DO NOT correlate with the severity of pruritus, and the theory invoking endogenous opioids as the main cause has NOT been upheld.

Question 8

Management of biliary pruritus

Answer 8

Pruritus of chronic cholestatic liver disease is improved with

• cholestyramine, 4 to 16 g daily.
• Rifampin, 150 to 300 mg/day, may be effective but should be used with caution because it may cause hepatitis.

*Naltrexone, up to 50 mg/day, is useful but has significant side effects. If used, naltrexone should be started at 1 tablet (12.5 mg) and increased by 1 tablet every 3 to 7 days until pruritus improves.

• Sertraline, 75 to 100 mg/day, is another option.

*UVB phototherapy was effective in a small case series.

*Ursodeoxycholic acid is effective for the pruritus in intrahepatic cholestasis of pregnancy, but not for the itching from other causes.

*Liver transplantation is the definitive treatment for end-stage disease and provides dramatic relief from the severe pruritus

Question 9

occurs almost exclusively in women older than 30.

Itching may begin insidiously and may be the presenting symptom in a quarter to half of patients. With time, extreme pruritus develops in almost 80% of patients. This almost intolerable itching is accompanied by jaundice and a striking melanotic hyperpigmentation of the entire skin;

the patient may turn almost black, except for a hypopigmented “butterfly” area in the upper back.

Eruptive xanthomas, planar xanthomas of the palms (Fig. 4.3), xanthelasma, and tuberous xanthomas over the joints may be seen.

Dark urine, steatorrhea, and osteoporosis occur frequently.

LAB FINDINGS:
Serum bilirubin, alkaline phosphatase, serum ceruloplasmin, serum hyaluronase, and cholesterol values are increased. The antimitochondrial antibody test is positive. The disease is usually relentlessly progressive with the development of hepatic failure. Several cases have been accompanied by scleroderma.

Answer 9

Pruritus in Primary Biliary Cirrhosis

Fig. 4.3 Primary biliary cirrhosis with plane xanthomas.

Question 10

it is usually induced by temperature changes or several minutes after bathing. The cause is unknown.

Answer 10

Polycythemia vera

Question 11

Management of Pruritus in Polycythemia vera

Answer 11

1. Aspirin has been shown to provide immediate relief from itching; however, there is a risk of hemorrhagic complications.
2. PUVA and NB UVB are also effective. A marked improvement is noted after an average of six treatments, with complete remission often occurring in 2–10 weeks.
3. Paroxetine, 20 mg/day, produced clearing or near-complete clearing in a series of nine patients.
4. Interferon (IFN) alpha 2 has been shown to be effective for treating the underlying disease and associated pruritus.

Question 12

characterized by pruritus that usually first manifests and is most severe on the legs and arms. Extension to the body is common; however, the face, scalp, groin, axillae, palms, and soles are spared.

The skin is dry with fine flakes (Fig. 4.4).

Answer 12

Fig 4.4 Winter itch.

Asteatotic eczema, eczema craquelé, and xerotic eczema are other names for this pruritic condition.

Question 13

causes of winter itch

Answer 13

Frequent and lengthy bathing with plenty of soap during the winter is the most frequent cause. This is especially prevalent in elderly persons, whose skin has a decreased rate of repair of the epidermal water barrier and whose sebaceous glands are less productive.

Low humidity in overheated rooms during cold weather contributes to this condition In a study of 584 elderly individuals,

Question 14

management of winter itch

Answer 14

Treatment consists of educating the patient on using soap only in the axillae and inguinal area and lubricating the skin with emollients mmediately after showering. Preparations containing lactic acid or urea applied after bathing are helpful in some patients but may cause irritation and may worsen itching in patients with erythema and eczema.

For those with more severe symptoms, long-standing disease, or a significant inflammatory component, a regimen referred to as “soaking and smearing” is dramatically effective. The patient soaks in a tub of plain water at a comfortable temperature for 20 minutes before bedtime. Immediately on exiting the tub, without drying, triamcinolone, 0.025%–0.1% ointment, is applied to the wet skin. This will trap the moisture, lubricate the skin, and allow for excellent penetration of the steroid component. An old pair of pajamas is then donned, and the patient will note relief even on the first night. The nighttime soaks are repeated for several nights, after which the ointment alone suffices, with the maintenance therapy of limiting soap use to the axillae and groin, and moisturization after showering. Plain petrolatum may be used as the lubricant after the soaking if simple dryness without inflammation is present. Folliculitis may complicate this therapy.

Question 15

Pruritus is often centered on the anal or genital area (less frequently in both), with minimal or no pruritus elsewhere. Anal neurodermatitis is characterized by paroxysms of violent itching, when the patient may tear at the affected area until bleeding is induced. Manifestations are identical to lichen simplex chronicus elsewhere on the body. Specific etiologic factors should always be sought and generally can be classified as dermatologic disease, local irritants (which may coexist with colorectal and anal causes), and infectious agents.

Answer 15

Pruritus Ani

Question 16

characterized by fissures and a white, sodden epidermis.

Answer 16

Mycotic pruritus ani

Question 17

diagnosis of Mycotic pruritus ani is established by

Answer 17

oral red fluorescence under the Wood’s light.

Scrapings are examined directly with potassium hydroxide mounts, and cultures will usually reveal Candida albicans, Epidermophyton floccosum, or Trichophyton rubrum. Other sites of fungal infection, such as the groin, toes, and nails, should also be investigated.

Question 18

Treatment of pruritus ani

Answer 18

1. Meticulous toilet care should be followed, no matter what the cause of the itching. After defecation, the anal area should be cleansed whenever possible, washed with mild soap and water. Medicated cleansing pads (Tucks) should be used regularly.
2. An emollient lotion (Balneol) is helpful for cleansing without producing irritation.
3. Once the etiologic agent has been identified, a rational and effective treatment regimen may be started. Topical corticosteroids are effective for most noninfectious types of pruritus ani; however, use of topical tacrolimus ointment will frequently suffice and is safer.
4. Pramoxine, a nonsteroidal topical anesthetic, is also often effective, especially in a lotion form combined with hydrocortisone.
5. In pruritus ani, as well as in pruritus scroti and vulvae, it is sometimes best to discontinue all topical medications and treat with plain water sitz baths at night, followed immediately by plain petrolatum applied over wet skin. This soothes the area, provides a barrier, and eliminates contact with potential allergens and irritants.

Question 19

The scrotum of an adult is a susceptible site for circumscribed neurodermatitis (lichen simplex chronicus) (Fig. 4.5).

Answer 19

Fig. 4.5 Pruritus scroti

Question 20

Management of pruritus scroti

Answer 20

1. Topical corticosteroids are the mainstay of treatment, but caution should be exercised. The “addicted scrotum syndrome” may be caused by the use of high-potency topical steroidal agents. As with facial skin, after attempts to wean patients off the steroid, severe burning and redness may occur. Although usually seen after chronic use, this may occur even with short-term high-potency steroids. The scrotum is frequently in contact with inner thigh skin, producing areas of occlusion, which increases the penetration of topical steroid agents.
2. Topical tacrolimus ointment is useful in overcoming the effects of overuse of potent topical steroids. Another alternative is gradual tapering to less potent corticosteroids.
3. Other useful nonsteroidal alternatives include topical pramoxine, doxepin, and simple petrolatum, which is applied after a sitz bath as described for pruritus ani.

Question 21

most common causes Pruritus Vulvae

Answer 21

1. in a prospective series of 141 women with chronic vulvar symptoms, he most common causes were unspecified dermatitis (54%), lichen sclerosus (13%), chronic vulvovaginal candidiasis (10%), dysesthetic vulvodynia (9%), and psoriasis (5%). In prepubertal children, such itching is most frequently irritant in nature, and girls generally benefit from education about improved hygienic measures.
2. Vaginal candidiasis is a frequent cause of pruritus vulvae.
3. T. vaginalis
4. Contact dermatitis from sanitary pads, contraceptives, douche solutions, fragrance, preservatives especially in moist towelettes, colophony, benzocaine, corticosteroids, and a partner’s condoms may account for vulvar pruritus.
5. Urinary incontinence should also be considered.
6. Lichen sclerosus is another frequent cause of pruritus in the genital area in middle-age and elderly women. Lichen planus may involve the vulva, resulting in pruritus and mucosal changes, including erosions and ulcerations, resorption of the labia minora, and atrophy.
7. When burning rather than itching predominates, the patient should be evaluated for signs of sensory neuropathy.

Question 22

Treatment of pruritus vulvae

Answer 22

1. Candidiasis and Trichomonas treatments are discussed in Chapters 15 and 20, respectively. Lichen sclerosus responds best to pulsed dosing of high-potency topical steroids or to topical tacrolimus or pimecrolimus.
2. Topical steroidal agents and topical tacrolimus may be used to treat psychogenic pruritus or irritant or allergic reactions.
3. The use of silk fabric underwear may limit irritation. Patch testing will assist in identifying the inciting allergen. Highpotency topical steroids are effective in treating lichen planus, but other options are also available (see Chapter 12).
4. Topical lidocaine, topical pramoxine, or an oral tricyclic antidepressant (TCA) may be helpful in select cases.
5. Phototherapy using a comb light device may be effective. Any chronic skin disease that does not respond to therapy should prompt a biopsy.

Question 23

consists of one or two intensely itchy spots in clinically normal skin, sometimes followed by the appearance of seborrheic keratoses at exactly the same site.

Answer 23

Puncta Pruritica (Itchy Points)

TREATMENT:
Curettage, cryosurgery, punch biopsy, or botulinum toxin A injection of the itchy points may cure the condition.

Question 24

itching evoked by contact with water of any temperature.

Most patients experience severe, prickling discomfort within minutes of exposure to water or on cessation of exposure to water

Answer 24

Aquagenic Pruritus

. . .

There are two groups of patients:

*about one third consist of an older, primarily male population who have polycythemia vera, hypereosinophilic syndrome, or myelodysplastic syndrome,

*and two thirds are younger women who develop aquagenic pruritus as young adults and who have no known underlying disease and may have a family history of similar symptoms.

Question 25

Treatment options for aquagenic pruritus include

Answer 25

the use of antihistamines, sodium bicarbonate dissolved in bath water, propranolol, atenolol, SSRIs, acetylsalicylic acid (ASA, aspirin), pregabalin, montelukast, and NB UVB or PUVA phototherapy. One patient found tight-fitting clothing settled the symptoms after only 5 minutes.

Question 26

widespread burning pain that lasted 15–45 minutes after water exposure, calling this reaction ______

Answer 26

AQUADYNIA

and considering the disorder a variant of aquagenic pruritus.

TREATMENT: Clonidine and propranolol seemed to provide some relief.

Question 27

what excludes inflammatory causes of scalp pruritus such as seborrheic dermatitis, psoriasis, dermatomyositis, or lichen simplex chronicus.?

Most such cases remain are neuropathic or idiopathic, but some represent chronic folliculitis.

Answer 27

Lack of excoriations, scaling, or erythema

Question 28

Treatment of Scalp Pruritus

Answer 28

Treatment with topical tar shampoos, salicylic acid shampoos, corticosteroid topical gels, mousse, shampoos, and liquids can be helpful. In patients who have severe scalp pruritus with localized itch, an intralesional injection of corticosteroid suspension may provide relief. Minocycline or oral antihistamines may be helpful. In other patients, low doses of antidepressants, such as doxepin, are useful.

Question 29

common drugs that causes drug-induced pruritus

Answer 29

Medications should be considered a possible cause of pruritus with or without a skin eruption.

1. opioid
2. chloroquine and to a
   lesser degree other antimalarials produce pruritus in many
   patients, especially African Americans, treated for malaria.
3. SSRIs and drugs causing cholestatic liver disease are other
   frequent causes.
4. Hydroxyethyl starch (HES) is used as a volume expander, a
   substitute for human plasma. One third of all patients treated
   will develop severe pruritus with long latency of onset (3–15
   weeks) and persistence. Up to 30% of patients have localized
   symptoms.

Antihistamines are ineffective.

Question 30

preferred term for the chronic itchy idiopathic dermatosis

Answer 30

Prurigo simplex

Question 31

Prurigo simplex is characterized by the lesion known as the __________________
which is dome shaped and topped with a
small vesicle.

The vesicle is usually present only transiently
because of its immediate removal by scratching, so that a
crusted papule is more frequently seen. these are present in various stages of development and are seen mostly
in middle-age or elderly persons of both genders.

The trunk
and extensor surfaces of the extremities are common sites,
symmetrically distributed. Other areas include the face, neck,
lower trunk, and buttocks. The lesions usually appear in crops,
so that papulovesicles and the late stages of scarring may be
seen at the same time.

Answer 31

prurigo papules

Question 32

histopathology of prurigo simplex

Answer 32

nonspecific but
often suggests an arthropod reaction. Spongiosis accompanied
by a perivascular mononuclear infiltrate with some eosinophils is often found.

Question 33

medications for initial treatment of prurigo simplex

Answer 33

topical corticosteroids and oral antihistamines. Early in the disease process, moderate-strength steroids should be used;

if the condition is found to be unresponsive, a change to high-potency forms is indicated.
Rebound may occur.

Intralesional injection of triamcinolone
will eradicate individual lesions.

For more recalcitrant disease,
UVB or PUVA therapy may be beneficial.

Question 34

rare dermatosis of unknown cause
characterized by the sudden onset of erythematous papules
or vesicles that leave reticulated hyperpigmentation when
they heal (Fig. 4-6).

The condition mainly affects Japanese,
although numerous cases have been reported in Caucasians.

It is associated with weight loss, dieting, anorexia, diabetes,
and ketonuria. It is exacerbated by heat, sweating, and friction and thus occurs most often in the winter and spring.

The areas most frequently involved are the upper back, nape, clavicular region, and chest. Mucous membranes are spared.

Answer 34

Prurigo pigmentosa

Question 35

A rare disorder most often found in Japan

is characterized by flat-topped, red-tobrown pruritic papules that spare the skinfolds, producing
bands of uninvolved cutis, the so-called deck-chair sign.

Answer 35

papuloerythroderma of Ofuji (PEO)

is characterized by flat-topped, red-tobrown pruritic papules that spare the skinfolds, producing
bands of uninvolved cutis, the so-called deck-chair sign.

Question 36

Histopathology of papuloerythroderma of Ofuji (PEO)

Answer 36

Frequently, there is associated blood eosinophilia. Skin
biopsies reveal a dense lymphohistiocytic infiltrate, eosinophils in the papillary dermis, and increased Langerhans cells.

Question 37

treatment of papuloerythroderma of Ofuji (PEO)

Answer 37

Systemic steroids are the treatment of choice and may result
in long-term remission. Topical or systemic steroids, tar derivatives, emollients, systemic retinoids, cyclosporine, UVB, and
PUVA may also be therapeutic. UV therapy, with or without
steroids, is favored.

Question 38

Also known as circumscribed neurodermatitis

results from long-term chronic rubbing and scratching, more vigorously than a normal pain threshold would
permit, with the skin becoming thickened and leathery.

The
normal markings of the skin become exaggerated (Fig. 4-7), so
that the striae form a crisscross pattern, producing a mosaic in
between composed of flat-topped, shiny, smooth quadrilateral
facets.

This change, known as lichenification, may originate on
seemingly normal skin or may develop on skin that is the site
of another disease, such as atopic or allergic contact dermatitis
or ringworm. Such underlying etiologies should be sought
and, if found, treated specifically. Paroxysmal pruritus is the
main symptom

Answer 38

Lichen simplex chronicus

Question 39

Treatment of Lichen simplex chronicus

Answer 39

Cessation of pruritus is the goal with lichen simplex chronicus.

A high-potency steroid cream or ointment should be used initially but not indefinitely because of the potential for steroid- induced atrophy. Occlusion of medium-potency steroids may be beneficial. Use of a steroid-containing tape to provide both occlusion and anti-inflammatory effects may have benefit. Treatment can be shifted to the use of medium- to lower- strength topical steroid creams as the lesions resolve.

Topical doxepin, capsaicin, or pimecrolimus cream or tacrolimus oint- ment provides significant antipruritic effects and is a good adjunctive therapy.

Intralesional injections of triamcinolone suspension, using a concentration of 2.5–5 mg/mL, may be required. Too superfi- cial an injection invites the twin risks of epidermal and dermal atrophy and depigmentation, which may last for many months. The suspension should not be injected into infected lesions because it may cause abscess.

Botulinum toxin A injection may be curative. In the most severe cases, complete occlusion with an Unna boot may break the cycle.

Question 40

A disease with multiple itchy nodules mainly on the extremities (Fig. 4.9), especially on the anterior surfaces of the thighs and legs.

Answer 40

Prurigo nodularis

A linear arrangement is common. The individual lesions are pea sized or larger, firm, and erythematous or brownish. When fully developed, they become verrucous or fissured. The course of the disease is chronic, and the lesions evolve slowly. Itching is severe but usually confined to the lesions themselves. Bouts of extreme pruritus often occur when these patients are under stress.

Prurigo nodularis is one of the disorders in which the pruritus is characteristically paroxysmal: intermittent, unbearably severe, and relieved only by scratching to the point of damag- ing the skin, usually inducing bleeding and often scarring.

The cause of prurigo nodularis is unknown; multiple factors may contribute, including atopic dermatitis, hepatic diseases (including hepatitis C), HIV disease, pregnancy, renal failure, lymphoproliferative disease, stress, and insect bites. Pem­ phigoid nodularis may be confused with prurigo nodularis clinically.

The histologic findings are those of compact hyperkeratosis, irregular acanthosis, and a perivascular mononuclear cell infil- trate in the dermis. Dermal collagen may be increased, espe- cially in the dermal papillae, and subepidermal fibrin may be seen, both evidence of excoriation. In cases associated with renal failure, transepidermal elimination of degenerated col- lagen may be found.

Question 41

treatment of prurigo nodular

Answer 41

The initial treatment of choice for prurigo nodularis is intralesional or topical administration of steroids. Usually,
superpotent topical products are required, but at times, lowerstrength preparations used with occlusion may be beneficial,
as when administered as the “soak and smear” regimen. The
use of steroids in tape (Cordran) and prolonged occlusion with
semipermeable dressings, such as used for treating nonhealing
wounds, can be useful in limited areas. Intralesional steroids
will usually eradicate individual lesions, but unfortunately,
many patients have too extensive disease for these local measures. PUVA, NB UVB, and UVA alone have been shown to be
effective in some patients. Vitamin D3 ointment, calcipotriene
ointment, or tacrolimus ointment applied topically twice daily
may be therapeutic and steroid sparing. Isotretinoin, 1 mg/
kg/day for 2–5 months, may benefit some patients. Managing
dry skin with emollients and avoidance of soap, with administration of antihistamines, antidepressants, or anxiolytics, is of
moderate benefit in allaying symptoms.
Good results have been obtained with thalidomide, lenalidomide, pregabalin, and cyclosporine. With thalidomide, onset
may be rapid or slow, and sedation may occur; initial dose is
100 mg/day, titered to the lowest dose required. Patients
treated with thalidomide are at risk of developing a dosedependent neuropathy at cumulative doses of 40–50 g.
Lenalidomide, an analogue of thalidomide, has less problems
with neuropathy but may cause myelosuppression, venous
thrombosis, and Stevens-Johnson syndrome. Pregabalin,
75 mg/day for 3 months, improved 23 of 30 patients in one
study. Cyclosporine at doses of 3–4.5 mg/kg/day has also
been shown to be effective in treating recalcitrant disease.
Cryotherapy may be used adjunctively.

Question 42

Psychodermatology

Answer 42

Some purely cutaneous disorders are psychiatric in nature,
their cause being directly related to psychopathologic causes
in the absence of primary dermatologic or other organic
causes. Delusions of parasitosis, psychogenic (neurotic) excoriations, factitial dermatitis, and trichotillomania compose the
major categories of psychodermatology. The differential diagnosis for these four disorders is twofold, requiring the exclusion of organic causes and the definition of a potential
underlying psychological disorder. Bromidrosiphobia is
another delusional disorder. Body dysmorphic disorder is a
spectrum of disease; some severely affected patients are delusional, whereas others have more insight and are less functionally impaired.

Psychosis is characterized by the presence of delusional ideation, which is defined as a fixed misbelief that is not shared
by the patient’s subculture. Monosymptomatic hypochondriacal disorder is a form of psychosis characterized by delusions
regarding a particular hypochondriacal concern. In contrast to
schizophrenia, there are no other mental deficits, such as auditory hallucination, loss of interpersonal skills, or presence of
other inappropriate actions. Patients with monosymptomatic
hypochondriacal psychosis often function appropriately in
social settings, except for a single fixated belief that there is a
serious problem with their skin or with other parts of their
body.

Question 43

Skin Signs of Psychiatric Illness

Fig. 4.10 Onychophagia. (Courtesy Curt Samlaska, MD.)

Answer 43

The skin is a frequent target for the release of emotional
tension. Some of the signs described here may become repetitive compulsions that impair normal life functions and may be
manifestations of an obsessive-compulsive disorder. Selfinjury by prolonged, compulsive repetitious acts may produce
various mutilations, depending on the act and site of injury.
Self-biting may be manifested by biting the nails (onychophagia) (Fig. 4-9), skin (most frequently the forearms, hands, and fingers), and lip. Dermatophagia is a habit or compulsion,
conscious or subconscious. Bumping of the head produces
lacerations and contusions, which may be so severe as to
produce cranial defects and life-threatening complications.
Compulsive repetitive handwashing may produce an irritant
dermatitis of the hands (Fig. 4-10).
Bulimia, with its self-induced vomiting, results in Russell’s
sign—crusted papules on the dorsum of the dominant hand
from cuts by the teeth. Clenching of the hand produces swelling and ecchymosis of the fingertips and subungual hemorrhage. Self-inflicted lacerations may be of suicidal intent. Lip
licking produces increased salivation and thickening of the
lips. Eventually, the perioral area becomes red and produces
a distinctive picture resembling the exaggerated mouth
makeup of a clown (Fig. 4-11). Pressure produced by binding
the waistline tightly with a cord will eventually lead to atrophy
of the subcutaneous tissue.
Psychopharmacologic agents, especially the newer atypical
antipsychotic agents, and behavioral therapy alone or in combination with these agents are the treatments of choice.

Question 44

firm fixation in a person’s mind that he or she suffers from a parasitic infestation of the skin.

Answer 44

Delusions of parasitosis (e.g., delusional parasitosis, Ekbom
syndrome, acarophobia, dermatophobia, parasitophobia,
entomophobia, pseudoparasitic dysesthesia)

. . .

so fixed that the patient may pick small
pieces of epithelial debris from the skin and bring them to be
examined, always insisting that the offending parasite is contained in such material. Samples of alleged parasites enclosed
in assorted containers, paper tissue, or sandwiched between
adhesive tape are so characteristic that it is referred to as the
“matchbox” or “ziplock” sign. Usually, the only symptom is
pruritus or a stinging, biting, or crawling sensation. Intranasal
formication, or a crawling sensation of the nasal mucosa, is
common in this condition. Cutaneous findings may range
from none to excoriations, prurigo nodularis, and frank
ulcerations

. . .
A skin biopsy is frequently performed, more to reassure the
patient than to uncover occult skin disease. Screening laboratory tests to exclude systemic disorders should be obtained:
CBC; urinalysis; liver, renal, and thyroid function tests; iron
studies; serum glucose and serum B12; folate; and electrolyte
levels. Once organic causes have been eliminated, the patient
should be evaluated to determine the cause of the delusions.
Schizophrenia, monosymptomatic hypochondriacal psychosis, psychotic depression, dementia, and depression with
somatization are considerations in the differential diagnosis.

Question 45

Management of Delusions of parasitosis

Answer 45

Although referral to a psychiatrist may seem best, most frequently the patient
will reject suggestions to seek psychiatric help. The dermatologist is cautioned against confronting the patient with the psychogenic nature of the disease. It is preferable to develop trust,
which will usually require several visits.

If pharmacologic,
1. Pimozide was the long-standing treatment of choice but is associated with a variety of side effects including stiffness, restlessness, prolongation of Q-T interval,
and extrapyramidal signs. Patients often respond to relatively
low dosages, in the 1–4 mg range, which limits these problems.

2. Pimozide is approved for the treatment of Tourette syndrome,
   and patients should understand the labeling before obtaining
   the drug.
3. risperidone and olanzapine have fewer side effects and are now
   considered the appropriate FIRST- LINE agents for the treatment
   of delusions of parasitosis, although the experience with them
   is more limited. With appropriate pharmacologic intervention,
   at least 50% of patients will likely remit.

Question 46

Many persons have unconscious compulsive habits of picking at themselves, and at times the tendency is so persistent and pronounced that excoriations of the skin result.

Answer 46

Psychogenic (neurotic) excoriations or excoriation disorder or skin picking disorder

. . .
The excavations may be superficial or deep and are often
linear. The bases of the ulcers are clean or covered with a scab.
Right-handed persons tend to produce lesions on their left side
and left-handed persons on their right side. There is evidence
of past healed lesions, usually with linear scars, or rounded
hyperpigmented or hypopigmented lesions, in the area of the
active excoriations. The face, upper arms, and upper back are
common sites for these excoriations (Fig. 4-12). Sometimes the
focus is on acne lesions, producing acne excoriée

. . .
The treatment of choice is doxepin because of its antidepressant and antipruritic effects; doses are slowly increased to
100 mg or higher, if tolerated. Many alternatives to doxepin
may be indicated, especially in those affected by an obsessivecompulsive component, including clomipramine, paroxetine,
fluoxetine, and sertraline. Other useful drugs are desipramine,
buspirone, and rapid-acting benzodiazepines. Treatment is
difficult, often requiring a combined psychiatric and pharmacologic intervention. It is important to establish a constructive
patient-therapist alliance. Training in diversion strategies
during “scratching episodes” may be helpful. An attempt
should be made to identify specific conflicts or stressors preceding onset. The therapist should concentrate on systematic
training directed at the behavioral reaction pattern. There
should be support and advice given with regard to the patient’s
social situation and interpersonal relations.

Question 47

has an unconscious goal of gaining attention and assuming the sick patient role

Fig. 4.13 Factitial ulcers and scarring.

Answer 47

Factitious dermatitis

Question 48

a neurosis characterized by an abnormal urge to pull out the
hair.

Answer 48

Trichotillomania (trichotillosis or neuromechanical alopecia)

. . .

The classic presentation is the “Friar Tuck” form of vertex and crown alopecia.
There are irregular areas of hair loss, which may be linear or
bizarrely shaped. Infrequently, adults may pull out pubic hair.
Hairs are broken and show differences in length (Fig. 4-14).
The pulled hair may be ingested, and occasionally the trichobezoar will cause obstruction. When the tail extends from the
main mass in the stomach to the small or large intestine,
Rapunzel syndrome is the diagnosis. The nails may show evidence of onychophagy (nail biting), but no pits are present.
The disease is seven times more common in children than in
adults, and girls are affected 2.5 times more often than boys.

Trichoscopy
reveals broken hairs of varying lengths; some may be frayed,
longitudinally split, or coiled. If necessary, a biopsy can be
performed and is usually quite helpful. It reveals traumatized
hair follicles with perifollicular hemorrhage, fragmented
hair in the dermis, empty follicles, and deformed hair shafts

(trichomalacia). Multiple catagen hairs are typically seen. An
alternative technique to biopsy, particularly for children, is to
shave a part of the involved area and observe for regrowth of
normal hairs. The differential diagnosis for this impulse
control disorder should include underlying comorbid psychopathology, such as an obsessive-compulsive disorder (most
common), depression, or anxiety.
In children, the diagnosis should be addressed openly, and
referral to a child psychiatrist for cognitive-behavioral therapy
(CBT) should be encouraged. Habit-reversal training is often
part of the treatment. In adults with the problem, psychiatric
impairment may be severe. Pharmacotherapy with clomipramine is the most effective of the studied medications, but
SSRIs are most often prescribed and may help any associated
depression or anxiety. N-acetylcysteine also shows promise; it
is available in health food stores and is relatively inexpensive
and well tolerated. Trichobezoars require surgical removal.

Question 49

a cutaneous neurosis characterized by a
patient’s uncontrollable desire to rub or pinch themselves to
form bruised areas on the skin, sometimes as a defense against
pain elsewhere.

Answer 49

Dermatothlasia

Question 50

is a monosymptomatic delusional state in which a person is convinced
that his or her sweat has a repugnant odor that keeps other
people away. The patient is unable to accept any evidence to
the contrary. Three quarters of patients with bromidrosiphobia are male, with an average age of 25. Atypical antipsychotic
agents or pimozide may be beneficial. It may be an early
symptom of schizophrenia.

Answer 50

Bromidrosiphobia (delusions of bromhidrosis)

Question 51

is the excessive preoccupation of
having an ugly body part. It is most common in young adults
of either gender. The concern is frequently centered about the
nose, mouth, genitalia, breasts, or hair. Objective evaluation
will reveal a normal appearance or slight defect. These patients
are usually seen in dermatologic practice, especially among
those presenting for cosmetic surgery evaluation. Patients may
manifest obsessional features, spending long periods inspecting the area. Associated depression and social isolation along
with other comorbidities present a high risk of suicide. The
SSRIs accompanied by CBT give the best results for those with
this somatoform disorder. More severely affected patients have delusions that may lead to requests for repeated surgeries of the site and require antipsychotic medications.

Answer 51

Body dysmorphic disorder (dysmorphic
syndrome, dysmorphophobia)

Question 52

characterized by pain
and burning sensations without objective findings. Many
patients report coexisting pruritus or transient pruritus associated with the dysesthesia.

Answer 52

Cutaneous dysesthesia syndromes

Question 53

occurs primarily
in middle-age to elderly women. Cervical spine degenerative
disk disease was found in 14 of 15 patients. The hypothesis is
that chronic tension is placed on the occipitofrontalis muscle
and scalp aponeurosis. In one series, gabapentin helped four
of the seven patients seen in follow-up. A psychiatric overlay
is frequently associated, and treatment with low-dose antidepressants may also be helpful.

Answer 53

Scalp dysesthesia

Question 54

Burning mouth syndrome (BMS)

Answer 54

is divided into two forms: a
primary type characterized by a burning sensation of the oral
mucosa, with no dental or medical cause, and secondary BMS,
caused by a number of conditions, including lichen planus,
candidiasis, vitamin or nutritional deficiencies (e.g., low B12,
iron, or folate), hypoestrogenism, parafunctional habits, diabetes, dry mouth, contact allergies, cranial nerve injuries, and
medication side effects. Identification of the underlying condition and its treatment will result in relief of secondary BMS.
Primary BMS occurs most frequently in postmenopausal
women. They are particularly prone to a feeling of burning of
the tongue, mouth, and lips, with no objective findings. Symptoms vary in severity but are more or less constant. Patients
with BMS often complain that multiple oral sites are involved.
Management with topical applications of clonazepam, capsaicin, doxepin, or lidocaine can help. Oral administration of
α-lipoic acid, SSRIs or tricyclic antidepressants (TCAs), gabapentin, and benzodiazepines has been reported to be effective.
The most common, best studied, and most successful therapy
is provided by the antidepressant medications, because many
patients are depressed as well.
Burning lips syndrome may be a separate entity; it appears
to affect both men and women equally and occurs in individuals between ages 50 and 70. The labial mucosa may be smooth
and pale, and the minor salivary glands of the lips are frequently dysfunctional. Treatment with α-lipoic acid showed
improvement in 2 months in a double-blind controlled
study.

Question 55

defined as vulvar discomfort, usually described
as burning pain, occurring without medical findings. It is
chronic, defined as lasting 3 months or longer

Answer 55

Vulvodynia

Question 56

unilateral sensory neuropathy characterized by infrascapular pruritus, burning pain, hyperalgesia, and tenderness, often in the distribution of the second to
sixth thoracic spinal nerves.

Answer 56

Notalgia paresthetica

. . .

A pigmented patch localized to
the area of pruritus is often found, caused by postinflammatory change. Macular amyloidosis may be produced by chronic
scratching. In most patients, degenerative changes in the
corresponding vertebrae are seen, leading to spinal nerve
impingement. When this is present, physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), gabapentin, oxycarbazepine, and muscle relaxants may be helpful, as may
paravertebral blocks.
Topical capsaicin or lidocaine patch has been effective, but
relapse occurs in most patients after discontinuing use. Botulinum toxin A injections were reported to be successful,
although an RCT failed to show efficacy. Excellent long-term
results may occur, and injections may be repeated as necessary. NB UVB is also an option.

Question 57

This condition is characterized by itching localized to the brachioradial area of the arm. To relieve the burning, stinging, or
even painful quality of the itch, patients will frequently use ice
packs

Answer 57

Brachioradial pruritus

. . .
The majority will have the sun-induced variety, a variant
of polymorphous light syndrome that usually responds well
to broad-spectrum sunscreens (see Chapter 3). In the remaining patients, cervical spine pathology is frequently found on
radiographic evaluation. Searching for causes of the abnormality should include discussion of spinal injury, such as trauma,
arthritis, or chronic repetitive microtrauma, whiplash injury,
or assessment for a tumor in the cervical spinal column.

TREATMENT

Gabapentin, botulinum A toxin, topical amitriptylineketamine or capsaicin, aprepitant, carbamazepine, cervical
spine manipulation, neck traction, anti-inflammatory medications, physical therapy, and surgical resection of a cervical rib
have all been successful in individual patients with brachioradial pruritus.

Question 58

Persistent numbness and periodic transient episodes of
burning or lancinating pain on the anterolateral surface of the
thigh characterize Roth-Bernhardt disease. The lateral femoral
cutaneous nerve innervates this area and is subject to entrapment and compression along its course.

Answer 58

Meralgia paresthetica (Roth-Bernhardt disease)

. . .

The diagnostic test of choice is somatosensory-evoked
potentials of the lateral femoral cutaneous nerve. Local anesthetics (e.g., lidocaine patch), NSAIDs, rest, avoidance of
aggravating factors, and weight reduction may lead to
improvement; indeed, 70% of patients have spontaneous
improvement, aided by conservative measures. Gabapentin is
useful in various neuropathic pain disorders. If such interventions fail and a nerve block rapidly relieves symptoms, local
infiltration with corticosteroids is indicated. Surgical decompression of the lateral femoral cutaneous nerve can produce
good to excellent outcomes but should be reserved for patients
with intractable symptoms who responded to nerve blocks but
not corticosteroids. If the nerve block does not result in
symptom relief, computed tomography (CT) scan of the
lumbar spine as well as pelvic and lower abdominal ultrasound examinations to assess for tumors are indicated.

Question 59

characterized by burning
pain, hyperesthesia, and trophic disturbances resulting from
injury to a peripheral nerve. The continuing pain is disproportionate to the injury, which may have been a crush injury,
laceration, fracture, hypothermia, sprain, burn, or surgery. It
usually occurs in one of the upper extremities, although leg
involvement is also common.

Answer 59

Complex regional pain syndrome

. . .
The characteristic symptom is
burning pain aggravated by movement or friction. The skin of
the involved extremity becomes shiny, cold, and atrophic and
may perspire profusely. Additional cutaneous manifestations
include bullae, erosions, edema, telangiectases, hyperpigmentation, ulcerations, and brownish red patches with linear fissures (Fig. 4-15).

. . .
The four
major components are categorized as sensory, vasomotor,
sudomotor/edema, and motor/trophic. Signs pertaining to at
least two of these categories and symptoms relating to three
are necessary to meet the BUDAPEST diagnostic criteria. A threephase technetium bone scan is helpful in CONFIRMING the diagnosis of CRPS.

Question 60

Interruption of the peripheral or central sensory pathways of
the trigeminal nerve may result in a slowly enlarging, unilateral, uninflamed ulcer on ala nasi or adjacent cheek skin (Fig.
4-16).The nasal tip is spared. It may infrequently occur elsewhere on the face, scalp, ear, or palate. The neck has been
reported to be affected in the so-called cervical trophic syndrome, secondary to herpes zoster–associated nerve injury.

Answer 60

Trigeminal trophic syndrome

. . .
Biopsy to exclude tumor or a variety of granulomatous or infectious etiologies is usually indicated. The cause
is self-inflicted trauma to the anesthetic skin; the appropriate
treatment is to prevent this by occlusion or with psychotropic medication, which is usually successful. Scarring may be
severe.

Question 61

Also known as neuropathic ulceration or perforating ulcer of
the foot, mal perforans is a chronic ulcerative disease seen on
the sole in conditions that result in loss of pain sensation at a
site of constant trauma (Fig. 4-17). The primary cause lies in
the posterolateral tracts of the cord (in arteriosclerosis and
tabes dorsalis), lateral tracts (in syringomyelia), or peripheral
nerves (in diabetes or Hansen’s disease).

Answer 61

Mal perforans pedis

. . .
In most patients, mal perforans begins as a circumscribed
hyperkeratosis, usually on the ball of the foot. This lesion becomes soft, moist, and malodorous and later exudes a thin,
purulent discharge. A slough slowly develops, and an indolent necrotic ulcer is left that lasts indefinitely. Whereas the
neuropathy renders the ulceration painless and walking continues, plantar ulcers in this condition have a surrounding
thick callus. Deeper perforation and secondary infection often
lead to osteomyelitis of the metatarsal or tarsal bones.

. . .

Treatment consists of relief of pressure on the ulcer through
use of a total-contact cast and debridement of the surrounding
callosity. Removable off-loading devices were found to be significantly less effective in a systematic review and metaanalysis. Administration of local and systemic antibiotics is
sometimes helpful.

Question 62

can result from improperly performed injections into the buttocks. Older patients are more
susceptible to injection-induced sciatic nerve injury because of
their decreased muscle mass or the presence of debilitating
disease. The most common scenario for nerve damage is
improper needle placement. Other common causes of sciatic
neuropathy are hip surgery complications, hip fracture and
dislocation, and compression by benign and malignant tumors.
A paralytic footdrop is the most common finding. There is
sensory loss and absence of sweating over the distribution of
the sciatic nerve branches. The skin of the affected extremity
becomes thin, shiny, and often edematous.
Surgical exploration, guided by nerve action potentials, with
repair of the sciatic nerve is worthwhile and is most successful
if done soon after injury.

Answer 62

Serious sciatic nerve injury

Question 63

results from cystic cavities inside the cervical
spinal cord caused by alterations of cerebrospinal fluid flow.
Compression of the lateral spinal tracts produces sensory and
trophic changes on the upper extremities, particularly in the
fingers. The disease begins insidiously and gradually causes
muscular weakness, hyperhidrosis, and sensory disturbances,
especially in the thumb and index and middle fingers. The skin
changes are characterized by dissociated anesthesia with loss
of pain and temperature sense but retention of tactile sense.
Burns are the most frequent lesions noted. Bullae, warts, and
trophic ulcerations occur on the fingers and hands, and eventually contractures and gangrene occur. Other unusual features include hypertrophy of the limbs, hands, or feet and
asymmetric scalp hair growth with a sharp midline demarcation. The disease must be differentiated chiefly from Hansen’s
disease. Unlike Hansen’s disease, syringomyelia does not
interfere with sweating or block the flare around a histamine
wheal.
Early surgical treatment allows for improvement of symptoms and prevents progression of neurologic deficits.

Answer 63

Syringomyelia