Nummular Dermatitis (Nummular Eczema)

Nummular eczema was first described by Deverigie in 1857[2] as coin-shaped lesions on the upper extremities. Since then, it has been reported in all age groups and in all body areas but is most commonly found on the upper and lower extremities.[3] Lesions most often start as papules, which coalesce into plaques; they are usually scaly. Early lesions may be studded with vesicles containing serous exudate. Nummular eczema is usually very pruritic. Many precipitating factors have been reported, including dry skin, contact allergies, weather (particularly winter), nutritional issues, and emotional stress.

Nummular dermatitis is a condition confined to the skin.

Little is known about the pathophysiology of nummular eczema, but it is frequently accompanied or preceeded by xerosis. Like most other forms of dermatitis, the cause is likely to be a combination of epidermal lipid barrier dysfunction and an immunologic response. Dryness of the skin results in "leaking" of the epidermal lipid barrier; this allows environmental allergens and bacteria to penetrate the skin and induce an allergic or irritant immune response.[4, 5] This is supported by one study that showed that elderly patients with nummular dermatitis had increased sensitivity to environmental aeroallergens compared with age-matched controls. This impaired cutaneous barrier in the setting of nummular eczema may also lead to increased susceptibility to allergic contact dermatitis to materials such as metals, soaps, and chemicals.[6]

Nummular eczema has been associated with medications. Any medication that induces dryness of the skin can theoretically initiate nummular eczema, particularly diuretics and statins. Onset of severe, generalized nummular lesions has been reported in association with interferon and ribavirin therapy for hepatitis C.[7, 8] Other medications that influence immune response have also been reported to induce lesions of nummular eczema, including inhibitors of tumor necrosis factor[9] and guselkumab.[10] A review of 1662 Japanese women found that nummular eczema developed in almost 3% of patients undergoing breast reconstruction, assumed to be due to surgical cleansers or bandage tape.[11]

Onset has also been described in association with mercury in dental amalgams. Hypersensitivity to the metals in the mouth is posulated to be sufficient to drive an immune response that results in cutaneous nummular plaques.

Because of the intense pruritus associated with nummular eczema, the potential role of mast cells in the disease process has been investigated. Increased numbers of mast cells have been observed in lesional compared with nonlesional samples in persons with nummular dermatitis.

One study identified neurogenic contributors to inflammation in both nummular eczema and atopic dermatitis by investigating the association between mast cells and sensory nerves and identifying the distribution of neuropeptides in the epidermis and upper dermis of patients with nummular eczema. Researchers hypothesized that release of histamine and other inflammatory mediators from mast cells may initiate pruritus by interacting with neural C-fibers. The research showed that dermal contacts between mast cells and nerves were increased in number in both lesional and nonlesional samples of nummular eczema compared with normal controls. In addition, substance P and calcitonin gene-related peptide fibers were prominently increased in lesional samples compared with nonlesional samples from patients with nummular eczema. These neuropeptides may stimulate release of other cytokines and promote inflammation.[12, 13, 14]

Other research has demonstrated that mast cells present in the dermis of patients with nummular eczema may have decreased chymase activity, imparting reduced ability to degrade neuropeptides and protein. This dysregulation could lead to decreased capability of the enzyme to suppress inflammation.

Colonization of the skin with Staphylococcus aureus has been described both on lesional skin and in the nares of patients and their close contacts.[15] Whether this is important in the precipitation of disease has yet to be determined.

The etiology of nummular eczema is unknown and likely multifactorial. Most patients with nummular eczema also have very dry (xerotic) skin. Local trauma, such as arthropod bites, contact with chemicals, or abrasions, may precede an outbreak.

Contact dermatitis may play a role in some cases. Contact dermatitis may be irritant or allergic in nature. Sensitivity to nickel, cobalt, or chromates has been reported in patients with nummular dermatitis. In one study, the most frequent sensitizers were colophony, nitrofurazone, neomycin sulfate, and nickel sulfate. In the past, cases of nummular eczema–like eruptions have been caused by ethyl cyanoacrylate–containing glue, thimerosal,[16] mercury-containing dental amalgams,[17] and depilating creams containing potassium thioglycolate.[18] .  

Venous insufficiency (and varicosities), stasis dermatitis, and edema may be related to the development of nummular eczema on the affected lower extremities.[19]

Autoeczematization (ie, lesional spread from the initial focal site) may account for the presence of multiple plaques.

Onset of severe, generalized nummular lesions has been reported in association with interferon therapy for hepatitis C as well as exposure to mercury.19.  Various types of eczematous eruptions, including nummular eczema, have been observed following tumor necrosis factor-alpha–blocking therapy.[9]  and it has been reported after treatment of psoriasis with guselkumab as well.[20]  

Nummular eczema of the breast has reported in breast cancer patients undergoing mastectomy with subsequent breast reconstruction.[21, 22] .  The majority of these patients developed it after the insertion of tissue expanders or breast implants; the authors suggested a role in stretching of the skin as a cause.

Nummular eczema has been found in association with infection in rare cases. Giardiasis has been reported.[1] One study reported that in patients with Helicobacter pylori infection and nummular eczema, eradication of H pylori caused clearance of the skin lesions in 54% of the patients.[23] Another case report noted nummular eczema in association with a dental infection that cleared after the treatment of the infection.[24]

In children, it occurs most often in association with atopic dermatitis[25] .

Frequency

The prevalence of nummular eczema is two cases per 1000 people. Dermatitis in general (eg, atopic, asteatotic, dyshidrotic, nummular, hand) is one of the most common of dermatologic conditions.

Race

No racial predilection has been observed.  In children, it appears to be more common in those of skin of color[25] .

Sex

Nummular eczema is more common in males than in females (see Age below).

Age

Nummular eczema has two peaks of age distribution. The most common is in the sixth to seventh decade of life and is most often seen in males. A smaller peak occurs in the second to third decade of life, which is most often seen in association with atopic dermatitis. This is more often seen in females, by two thirds in one study.[26] It is uncommon in children.[27] .  Nummular eczema also occurs in children.

Nummular eczema tends to be a chronic condition that remits and relapses. Patients need to be informed that once nummular eczema develops, it is often recurrent. Avoidance of exacerbating factors and close attention to moisturizing the skin may help reduce the frequency.

Pruritus, often worst at night, may cause irritability, insomnia, or both.

Secondary infection may result in lesions that ooze serosanguineous exudate. The most common organism revealed by culture is Staphylococcus aureus.

Generalized flares may require systemic antibiotics and/or systemic steroids.

Increased contact sensitivity to environmental antigens (especially metals) could limit ability to tolerate those antigens, especially clothing, metal snaps, jewelry, dental amalgams or occupational exposure.

Patients must be educated about the most important predisposing condition to nummular eczema—dry skin. Use of gentle soaps and copious application of moisturizers, especially while the skin is still damp after bathing, is imperative. Once the lesions develop, use of topical steroids or calcineurin inhibitors helps with the itch and hastens resolution.

For patient education resources, visit the Skin Conditions and Beauty Center. Also, see the patient education article Eczema.

Patients present with days to months, or even years, of a pruritic eruption, which usually starts on the legs. It may also burn or sting.

Nummular eczema often waxes and wanes with winter; cold or dry climates or swings in temperature may be exacerbating factors. It may improve with sun or humidity exposure or with moisturizer use. Occasionally, it may worsen with heat or humidity.

Recurrent nummular eczema lesions often occur in the same locations as previous lesions.

The patient's medical history may be positive for eczema, atopic dermatitis, or dry and sensitive skin.

The diagnosis of nummular eczema is made on the basis of observing the characteristic round-to-oval erythematous plaques. They are most commonly located on the extremities, particularly the legs, but they may occur anywhere on the trunk, hands, or feet.[28] Nummular eczema does not usually involve the face or scalp. Lesions are often symmetrically distributed. Plaques may be several centimeters.

See the image below.

Dry, scaling plaque of nummular dermatitis (size, 3 X 5 cm) on the shin.

Lesions begin as erythematous-to-violaceous papules or vesicles, which then coalesce to form confluent plaques. They may have overlying erosions due to excoriation.

Early lesions, particularly vesicular ones, often become colonized by staphylococci, which produces a yellowish crust. Secondary overt infection may occur, with cellulitis surrounding the plaques, requiring oral antibiotics.

Within a few days, plaques become dry, scaly, and more violaceous, particularly when located below the knee.

The lesions then flatten to macules, usually with brown postinflammatory hyperpigmentation that gradually lightens. The pigment may never completely fade, particularly when located below the knee.

Lesions may demonstrate the yellow crusting of secondary impetiginization. Older plaques typically show scale that trails the lesional border.

Plaques may show central clearing, making differentiation from tinea corporis based on clinical findings difficult. Tinea corporis usually has few vesicles, a raised narrow border, and leading scale (ie, scale on the outside of the plaque).

Distinguishing among forms of dermatitis (eg, asteatotic eczema, atopic dermatitis, nummular eczema) may be difficult, but, fortunately, this is not necessary to make proper treatment decisions.[29] Contact dermatitis may have a pattern that approximates the manner in which the offending agent came into contact with the skin, such as a linear pattern. It may become chronic in the setting of repeated exposure, such as with chromates and formaldehyde. The patient may recall contact with an allergen, such as poison ivy.

Longstanding lesions that have been aggressively scratched may develop lichen simplex chronicus. This often occurs on the lower legs, neck, scalp, or scrotum. The typical erythema of nummular eczema becomes violaceous and thickened. Although the border of lichenified lesions remains well demarcated, in some areas it may become less so, particularly on the genitalia. Postinflammatory hyperpigmentation may occur, especially with involvement of the lower leg.  

Stasis dermatitis may occur simultaneously on the lower extremities, and venous stasis may lead to the concomitant development of both conditions.

Nummular eczema lesions may become secondarily infected. Heavily excoriated or infected lesions may leave permanent scars. Lesions on the lower extremities take a long time to heal and may leave permanent brown macules. Cellulitis rarely occurs. Particularly pruritic cases may result in difficulty sleeping and concentrating.

A skin biopsy may be performed. The findings are nonspecific, but they may help differentiate nummular dermatitis from tinea corporis, psoriasis, a fixed drug eruption, or cutaneous T-cell lymphoma.

Some studies have recommended patch testing in patients with refractory nummular dermatitis. One study found that 50% of 56 patients with nummular eczema showed positive reactions on patch testing, and other research identified positive patch testing in 23 of 50 patients with nummular dermatitis.[30, 31]  A 2012 study strongly recommended patch testing in nummular dermatitis, as it showed that 332 (32.5%) of 1022 patients with nummular dermatitis had positive patch test results for one or more allergens.[6]

Biopsy findings mirror the evolution of the lesion. In the early stages, a nonspecific infiltrate is present with spongiosis, vesicles, and a predominant lymphocytic infiltrate. Eosinophils may be observed in the papillary dermis. Chronic lesions demonstrate epidermal hyperplasia, hyperkeratosis, and a pronounced granular cell layer. The papillary dermis may be fibrotic, with a perivenular infiltrate of lymphocytes and monocytes.

Lymphocytes are predominately CD8+ in the epidermis and CD4+ in the dermis. Mast cell–derived interleukin 4 appears to be involved in activation of the T lymphocytes.

Hydration of the skin is the most important factor in treating nummular eczema. Use of hypoallergenic, fragrance-free creams, lotions, or ointments is the first step in therapy.

Treatment is aimed at rehydration of the skin, repair of the epidermal lipid barrier, reduction of inflammation and treatment of any infection. Medications and emollients are best absorbed by dampening the skin first.

Lukewarm or cool baths or showers reduce itching and help rehydrate the skin; a gentle soap or liquid cleanser may be used. Skin should be patted dry and then moisturizers are applied to still-damp skin. The "soak-and-smear" therapeutic regimen includes a 20-minute plain water soak each night followed by application of steroid ointment or petrolatum to wet skin and includes alteration of cleansing habits so that soap is applied only to the axilla and groin. One study showed greater than 90% response in 27 of 28 patients with refractory chronic pruritic eruptions when the regimen was followed as directed.[32]

Wet wrap treatments are often helpful. This involves dampening the skin with lukewarm water until it is well hydrated (usually 10 min). Then, petrolatum or steroid ointment is applied liberally, followed by occlusion for 1 hour with damp pajamas or a nonbreathable sauna suit. For small areas of involvement, plastic wrap may be used to occlude the area. This process may be repeated 5-6 times a day with petrolatum. Caution must be used when prescription steroid medications are used because overuse of these medications can cause striae, thinning of the skin, and, rarely, enough systemic absorption of steroid to affect the hypothalamic-pituitary-adrenal axis.

Steroids are the most commonly used therapy to reduce inflammation. Less erythematous, less pruritic lesions may be treated with low-potency (class III-VI) steroids. Severely inflamed lesions with intense erythema, vesicles, and pruritus require high-potency (class I-II) preparations. Penetration of the medication is enhanced by occlusion and/or presoaking in a tub of plain water followed immediately (without drying) by application of the steroid-containing ointment.

Ointments are usually more effective than creams because they are more occlusive, form a barrier between the skin and the environment, and more effectively hold water into the skin. However, patients may be more likely to use a cream formulation; education and discussion is key to patient compliance.

Oral, intramuscular, or parenteral steroids may be required in cases of severe, generalized eruptions.

Tar preparations are helpful to decrease inflammation, particularly in older, thickened, scaly plaques.

Topical immune modulators (tacrolimus and pimecrolimus) also reduce inflammation.[33] These are often initiated a few days after the topical steroid to decrease the risk of a burning sensation that may occur when applied to extremely irritated skin. Other topical treatments that are currently approved for atopic dermatitis may be helpful, including crisaborole and topical ruxolitanib, though data specifically for nummular eczema is lacking.

When eruptions are generalized and prolonged, more aggressive therapy is warranted. Systemic steroids have long been a mainstay for the treatment of dermatitis, including nummular eczema, though it ahould only be used with short courses and when topical treatmetn has been insufficient.  Cyclosporine A has been used as an alternative to systemic steroids, though requires monitoring of blood pressure and renal function.  Phototherapy (generally with ultraviolet [UV] B) may be helpful.[34] Broadband or narrowband UVB is most commonly used, although psoralen plus UVA (PUVA) may be used in severe cases. Oral immunosuppressive agents may help to attenuate the immune response; methotrexate has been used successfully in children with nummular eczema.[35] Data are lacking for other immunosuppressants such as azathioprine and mycophenolate mofetil in the treatment of nummular eczema, although these medications have been used in other forms if dermatitis. Dupilumab, a monoclonal antibody targeting interleukins 4 and 13, has also been used successfully to treat  nummular eczema[36] . Treatment with inhibitors of JAK kinase has not been reported, but given success in atopic dermatitis these medications may develop a role in treating extremely refractory cases of nummular eczema.

Mindfulness-based therapies, including meditation and hypnotherapy, have also been reported to be helpful.[37]

Oral antihistamines or sedatives may help reduce itching and improve sleep. Topical antihistamines are known to be potent topical sensitizers, and, thus, preparations containing topical diphenhydramine in particular should not be used. Oral gabapentin and pregabalin as well as opioid receptor antagonists may be more efficacious in treating itching due to nummular eczema.[38]

Topical antibiotics such as mupirocin may help impetiginization; as neomycin- or bacitracin-containing medications are potent topical sensitizers, these should be avoided.

Oral antibiotics, such as dicloxacillin, cephalexin, or erythromycin, should be used in cases of secondary infection. Swab cultures of the skin guide selection of antibiotics.

Once the eruption has resolved, ongoing aggressive hydration may decrease the frequency between flares, particularly in dry climates. Heavy moisturizers (preferably a sensitive-skin formulation) or petroleum jelly applied to damp skin after showering may be helpful.

Disease may be severe and refractory to the above treatments. Immune-suppressive medications such as methotrexate have been described to be safe and effective in these severely affected patients.[39, 35]

Because lesions are persistent and may be difficult to treat, consultation with a dermatologist in an outpatient setting may be advisable.

Activities that heat or dry the skin worsen the pruritus and the eruption. Resting in a cool, moist environment is therapeutic. Heat, soap, drying conditions, and irritating activities should be avoided. Extreme cold may also exacerbate nummular eczema.

Sunlight or phototherapy may be beneficial, particularly in chronic cases. Ultraviolet radiation helps reduce the inflammatory activity within the skin. The risk of heat worsening the pruritus and of ultraviolet light inducing cutaneus malignancies must be weighed against the potential benefits.

Aggressive hydration of the skin may decrease the frequency between nummular dermatitis eruptions.

Bathing is permissible, but hot water should be avoided. Patients should use mild, nondrying cleansers. Patients should be encouraged to use nonsoap cleansers only for control of body odor and cleanliness (eg, on the groin, axillae, and feet). Oil additives may be used in bathing water. To avoid drying of the lesions, an emollient should be used immediately after bathing. The skin may be patted and the emollient applied before the skin is completely dry. Clothing should be loose to avoid overheating, and irritating fibers, such as wool, should be avoided.

A room humidifier is useful, particularly when a heater or air conditioning is used.

A potent-to-intermediate potency steroid may be applied 2-4 times daily to the affected areas. They are most effective when used in ointment form (rather than cream) and applied to damp skin. Once lesions improve, a lower-potency steroid or moisturizer should be prescribed to avoid skin atrophy.

If the patient has an overt infection, a combination of a topical antibiotic and a steroid ointment applied twice daily is usually very effective. This therapy decreases inflammation and colonization by staphylococci.

Use of sedating antihistamines at night helps with sleep.

Severe or generalized flares may be treated with tap water–moistened dressings on top of the steroid ointment. Oral or parenteral steroids may be used in severe flares, followed by topical therapy.

Oral antibiotics, such as dicloxacillin, cephalexin, or erythromycin, should be used in cases of secondary infection.

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. In addition, they modify the body's immune response to diverse stimuli.

Triamcinolone topical (Aristocort) Cream or Ointment

Triamcinolone topical is used for inflammatory dermatosis responsive to steroids; it decreases inflammation by suppressing migration of PMN leukocytes and reversing capillary permeability. It is a good choice once lesions stabilize and the threat of secondary infection has passed. Use 0.025-0.1% strength.

Prednisone (Deltasone, Meticorten, Orasone)

Prednisone is for severe generalized flares. It may decrease inflammation by reversing increased capillary permeability and suppressing PMN leukocyte activity.

Clobetasol (Clarelux, Clobex, Clobex Spray)

Clobetasol propionate is a class I superpotent topical steroid; it suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction. Clobetasol propionate decreases inflammation by stabilizing lysosomal membranes, inhibiting PMN and mast cell degranulation.

Class Summary

Immune modulators reduce inflammation.

Pimecrolimus 1% cream (Elidel)

Pimecrolimus is the first nonsteroid cream approved in the United States for mild-to-moderate atopic dermatitis. It is derived from ascomycin, a natural substance produced by fungus Streptomyces hygroscopicus var ascomyceticus. Pimecrolimus selectively inhibits production and release of inflammatory cytokines from activated T-cells by binding to cytosolic immunophilin receptor macrophilin-12. The resulting complex inhibits phosphatase calcineurin, thus blocking T-cell activation and cytokine release. Cutaneous atrophy was not observed in clinical trials, a potential advantage over topical corticosteroids. Pimecrolimus is indicated only after other treatment options have failed.

Tacrolimus 0.03% or 0.1% ointment (Protopic)

The mechanism of action of tacrolimus in atopic dermatitis is not known. It reduces itching and inflammation by suppressing the release of cytokines from T cells. It also inhibits transcription for genes that encode IL-3, IL-4, IL-5, GM-CSF, and TNF-alpha, all of which are involved in the early stages of T-cell activation. Additionally, tacrolimus may inhibit the release of preformed mediators from skin mast cells and basophils, and down-regulate expression of FCeRI on Langerhans cells. It can be used in patients as young as 2 years. Drugs of this class are more expensive than topical corticosteroids. Tacrolimus is available as an ointment in concentrations of 0.03 and 0.1%. It is indicated only after other treatment options have failed.

Class Summary

Antihistamines used to help with sleep. Caution must be used because even the traditionally nonsedating classes may cause somnolence.

Hydroxyzine (Atarax, Vistaril, Vistazine)

Hydroxyzine antagonizes H1 receptors in the periphery. It may suppress histamine activity in the subcortical region of the CNS. Hydroxyzine is a piperazine type of antihistamine that has fewer sedating effects compared with diphenhydramine and is effective. It is usually well tolerated in most individuals.

Class Summary

Antibiotics are used for severe exudative flares with infection. Empiric antimicrobial therapy should cover S aureus and other likely pathogens in the context of the clinical setting.

Sulfamethoxazole and trimethoprim (Bactrim)

Sulfamethoxazole and trimethoprim combination agent inhibits bacterial growth by inhibiting the synthesis of dihydrofolic acid. The antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except Pseudomonas aeruginosa. It is also used for MRSA infections.

Dicloxacillin (Dynapen, Pathocil, Dycill)

Dicloxacillin binds to one or more penicillin-binding proteins, which, in turn, inhibits the synthesis of bacterial cell walls. Dicloxacillin is used for the treatment of infections caused by penicillinase-producing staphylococci. It may be used to initiate therapy when staphylococcal infection is suspected.

Erythromycin (E.E.S., E-Mycin, Eryc)

Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is used for the treatment of staphylococcal and streptococcal infections.

In children, age, weight, and severity of infection determine proper dosage. When twice-daily dosing is desired, half the total daily dose may be taken every 12 hours. For more severe infections, double the dose.

Cephalexin (Biocef, Keflex, Keftab)

Cephalexin is a first-generation cephalosporin that arrests bacterial growth by inhibiting the synthesis of bacterial cell walls. It has bactericidal activity against rapidly growing organisms. Its primary activity is against skin flora. Cephalexin is used for skin infections or prophylaxis in minor procedures.

Dupilumab (Dupixent)

Dupimumab is a monoclonal antibody that blocks interleukins 4 and 13, which have been shown to be important mediators in atopic dermatitis.  It has been shown to be helpful in many other diseases including asthma, prurigo nodularis and eosinophilic esophagitis.

Cyclosporine (Gengraf, Neoral, Sandimmune)

Oral immune suppressant formerly used in solid organ and bone marrow transplants. Suppresses the immune system.  Use is limited due to renal toxicity and patients must be monitored aggressively with bloodwork and blood pressure.