The last new patient of the clinic session presented in moderate distress with extremely pruritic legs. She was 74 years old and accompanied by her husband. The patient complained of swollen legs and itchy sores that had failed to resolve with previously prescribed mometasone cream. She had seen multiple doctors and was frustrated that her legs were becoming worse.
Her past medical history included type 1 diabetes, hypertension and hyperlipidemia. She had major polypharmacy with 11 medications to control the big three diseases (hypertension, hyperlipidemia and diabetes) as well as early cognitive impairment, anxiety and gastroesophageal reflux disease.
The examination revealed that the patient’s legs were studded with erythematous papules and excoriated hyperpigmented plaques. However, no cellulitis was evident. Mild pitting edema was present. There were about a dozen ulcerated plaques with yellow bases about both lower legs, especially laterally and posteriorly. The pedal pulses were obscured by lymphedema while the feet were clear of any lesions. The vibratory threshold at the hallux interphalangeal joint was five out of 18 seconds bilaterally, which was consistent with moderately severe peripheral sensory neuropathy.
Although the patient complained of leg “swelling,” the calf and ankle circumferences were not disproportionate. The sensory neuropathy may help to explain that her “swelling” complaint was actually dysesthesias.
Key Questions To Consider
1. What questions should a physician ask the patient?
2. What is the diagnosis?
3. What factors can cause pruritus?
4. What are the four areas of consideration that can limit the differential diagnosis?
5. What is the proper treatment?
Answering The Key Diagnostic Questions
1. “Have you or anyone in your family ever had food allergies, hay fever, asthma or skin rashes?”
3. Stress, atopic diathesis, anxiety, depression
4. Consider your primary first impression, mimicking conditions, the worst case scenario and more obscure condition possibilities.
5. Replenish the local depletion of cortisol with topical corticosteroids, central sedation to suppress the itch-scratch cycle and prevent further lesion aggravation with protective dressings.
A Closer Look At Neurodermatitis
Patients often complain of itching but are reluctant to admit actual scratching. Many conditions in the lower extremity have a pruritic component. These conditions include inflammatory tinea, neurodermatitis or even cutaneous T-cell lymphoma.
Why do some skin conditions itch? The free nerve endings in the skin trigger withdrawal from noxious stimuli while minor stimulation initiates reflexive touching and rubbing. Stronger stimulation produces pain. These sensations transmit from both myelinated and unmyelinated fibers. Both pain and itch follow the spinothalamic tracts but by different pathways.1 Individual thresholds vary.
Atopic diathesis predisposes patients to pruritus. It normally takes 200 firm strokes to produce a skin rash in patients without atopy while patients with atopy have cutaneous hypersensitivity and develop a rash with only 20 strokes. General atopy is quite common, affecting 7 percent of the adult population.2 One can readily detect the likelihood of atopic eczema by asking patients if they or anyone in their family ever had food allergies, hay fever, asthma or skin rashes.
In cases with a psychogenic component, anxiety and depression are often the primary triggers of neurodermatitis. Excessive stress can cause a variety of symptoms in patients. Individuals may respond to excessive stress with headache, gastrointestinal symptoms or skin reactions. Detecting and mitigating the stressor is an important step in determining the diagnosis and developing a comprehensive management plan.
Some detective work may be involved to determine what instruments of perpetuation the patient is using. Many patients believe it is appropriate and necessary to scrape away almost any degree of normal callus formation from their heels as the beauty magazines recommend. This can lead to lichenification and spread of the lesions into thick hyperpigmented plaques.
Neurodermatitis presents as one stage in a spectrum of scratching or rubbing disorders in our patients. First, a solitary, localized coin-shaped plaque of nummular eczema develops. A single finger rubbing one reachable spot may initiate the condition. Repetitive rubbing can establish the itch-scratch cycle, which may progress to larger, thicker plaques of fissured lichenification within weeks. Some lesions may become excoriated. Secondary infection can develop. Months of continual itching and scratching produce thick plaques of lichen simplex chronicus and later nodules of prurigo nodularis. We can consider all of these manifestations of neurodermatitis as localized cutaneous zones of depleted cortisol, perpetuated by centralized reflex.
It is interesting to note that histologically, chronic neurodermatitis or lichen simplex chronicus are quite similar to pressure keratoses. Common features include hyperkeratosis, acanthosis and parakeratosis pointing to similar mechanisms of repetitive rubbing and friction. Shoes or a supporting surface that repetitively rubs skin over a prominent joint can produce localized hyperkeratotic plaques of lichen simplex chronicus.
A Guide To The Differential Diagnosis
Pujol and colleagues have listed 33 local and 38 systemic causes of persistent pruritus.3 Alarmingly, an invisible form of mycosis fungoides can present as pruritus without any rash and only a biopsy can diagnose it.4 Patients with persistent pruritus deserve a dermatology consult.
A laundry list of differential diagnoses can be confusing and slow down our clinical thinking. Nousari suggests simply limiting our list of differentials to the following four thought paths.5
1. Primary impression. At the top of your list should be what your gut tells you. This works well as long as it is a disease you have seen or heard of before.
2. Mimicker. What would be the chief mimicker of the primary impression? In this case, it should be a member of the papulosquamous family of disorders. Considering similar presentations, psoriasis is an appropriate mimicker. One can easily miss psoriasis when it presents solely on the foot without accompanying telltale extensor surface lesions. Inspecting the scalp, knees and elbows for scaly plaques is often helpful to confirm a clinical impression of pedal psoriasis.
3. Worst case scenario. What diagnosis, if missed, would cause the most harm to the patient? The group of cutaneous T-cell lymphomas may present with persistent pruritus and erythrodermic plaques. Biopsies and consultations are important in chronic lesions that do not improve with topical therapies.
4. Esoterica. In order to satisfy our intellectual need to consider the most remote of diagnostic possibilities, our differential diagnosis list would not be complete without a rare bird. Dermatitis herpetiformis rarely presents on the foot but it is appropriate to consider it in this case because of its characteristic symptoms of intense pruritus and excoriations. Dermatitis herpetiformis is an autoimmune blistering disorder associated with gluten-sensitive enteropathy. It classically affects the extensor elbows, knees, buttocks and back.6 One can diagnose this via cutaneous biopsy and direct immunofluorescence showing deposition of immunoglobulin A in a granular pattern in the upper papillary dermis. Treatment is based on a gluten-free diet and dapsone (Aczone, Allergan).6
Mentally listing these four categories — primary impression, mimicker, worst case and esoterica — and then methodologically ruling each entity in or out will help get us started toward a comprehensive workup, arrival at the best diagnosis and the most effective management.
Key Insights Into Treatment And Prevention
Management of neurodermatitis basically relies on localized topical corticosteroids for inflammation control, central sedation to suppress the itch-scratch cycle and prevention of further scratching.
Topical corticosteroids have three clinically useful mechanisms of action. First, cutaneous vasoconstriction works to reduce erythema and “get the red out.” Secondly, there is the anti-pruritic effect to help break up the itch-scratch cycle. Finally, topical corticosteroids are strong immune system blockers.7
Central nervous system sedation may be necessary to break the itch-scratch cycle. Hydroxyzine (Vistaril, Pfizer) can help to centrally control anxiety and antagonize peripheral H1 receptors. Topical doxepin (Silenor, Somaxon Pharmaceuticals) antagonizes central H1 receptors and inhibits norepinephrine and serotonin reuptake.7 Research has shown gabapentin (Neurontin, Pfizer) and pregabalin (Lyrica, Pfizer) to relieve severe uremic pruritus.8
In the preventative phase of treatment, moisturizers and antipruritics with menthol and N-palmitoyl-ethanolamine help repair the epidermal barrier and act as safe substitutes for scratching.9 Ice can also help block the localized itch sensation.
In the acute phase of treatment, applying an Unna boot from the malleoli to the tibial tubercles helps to reduce stasis, lowers bacterial counts and acts as a barrier to continued scratching. Occluding the lesions is likely to result in better cure rates than the application of topical agents alone.10 After application of antibiotic ointment and triamcinolone (Kenalog, Bristol-Myers Squibb) to each open lesion, loosely apply the zinc oxide paste impregnated elastic gauze directly to the skin akin to a surgical dressing without tension. Then apply a layer of cotton cast padding and finally secure it with an elastic self-adherent wrap.
Patient education can help prevent the repetitive rubbing that initiates and perpetuates this disorder. Those patients with personality traits of excessive pain avoidance, dependency on other people’s desires, and who are more conforming and dutiful are more likely to develop skin disorders.10
Techniques of stress management are often important aspects of neurodermatitis. Discussing the importance of exercise, rest and sleep is helpful. Patients should avoid managing stress with food, caffeine and alcohol. Consultation with a mental health professional can help the patient practice coping measures to reduce stress and pruritus. In patients with diabetes, research has shown that stress management improves HgA1c by 0.5 percent.11
Preparing patients for expected recurrences of acute lesions should be part of the long-term management plan. Patients may interpret recurrent flares as failed treatment from the previous physician. Sequential photographic images are useful to assess progress visually in a disease that is chronic and recurrent in nature.
Management of neurodermatitis basically relies on replenishment of the local depletion of cortisol with topical corticosteroids, some form of central sedation to suppress the itch-scratch cycle and prevention of further lesion aggravation with protective dressings.
Dr. Bodman is an Associate Professor at the Kent State University College of Podiatric Medicine. He is a Diplomate of the American Board of Podiatric Medicine. Dr. Bodman is in private practice in Ohio.
1. Ward JR, Bernhard JD. Pruritus. In: Lebwohl M, Heymann WR, et al. (eds): Treatment of Skin Disease. 2nd ed. Mosby Elsevier, St. Louis, 2006, pp. 533-537.
2. Küster W, Petersen M, Christophers E, et al. A family study of atopic dermatitis. Arch Dermatol Res. 1990; 282(2):98-102.
3. Taylor JS, Zirwas MJ, Sood A. Pruritus. Available at http://tinyurl.com/dly5b5 . Published August 2010. Accessed July 29, 2013.
4. Pujol RM, Gallardo F, Llistosella E, et al. Invisible mycosis fungoides: A diagnostic challenge. J Am Acad Dermatol 2002; 47(2Suppl):S167-S171.
5. Nousari CH. Immunofluorescence of vasculitis. Presented at the American Podiatric Medical Association Annual Scientific Meeting, Washington, DC, August 2012.
6. Miller JL, Elston DM, et al. Dermatitis herpetiformis. Available at http://emedicine.medscape.com/article/1062640-overview . Published June 24, 2013. Accessed July 29, 2013.
7. Giovanielli KR. Pruritus. In Arndt A, Hsu TS (eds). Manual of Dermatologic Therapeutics, 7th edition, Lippincott Williams & Wilkins, Philadelphia, 2007.
8. Rayner H, Baharani J, Smith S, et al. Uraemic pruritus: relief of itching by gabapentin and pregabalin. Nephron Clin Pract. 2012; 122(3-4):75-9.
9. Eberlein B, Eicke C, Reinhardt HW, Ring J. Adjuvant treatment of atopic eczema: assessment of an emollient containing N-palmitoylethanolamine (ATOPA study). J Eur Acad Dermatol Venereol. 2008 Jan;22(1):73-82.
10. Tey HL, Wallengren J, Yosipovitch G. Psychosomatic factors in pruritus. Clin Dermatol. 2013; 31(1):31-40.
11. Surwit RS, van Tilburg MA, Zucker N, et al. Stress management improves long-term glycemic control in type 2 diabetes. Diabetes Care. 2002; 25(1):30-4.