A 50-year-old woman with no significant medical history presented with complaints of an enlarging, erythematous eruption. The lesions started three weeks earlier as pink papules on her shoulders, back, and buttocks. Mild pruritus was relieved with diphenhydramine (Benadryl). The woman had also been treating the lesions with an OTC antifungal with no relief. She had no complaints of pain, no history of new medications or recent travel, and no pets in the household.
A man, aged 53 years, with a history of tobacco abuse, presented with a rash on his palms and soles that had begun three months earlier. He had been previously diagnosed with tinea manuum and tinea pedis. A three-month course of oral terbinafine (Lamisil, Terbinex) provided no relief of the eruption. He had no associated symptoms. On physical examination, erythematous scaling plaques that were studded with pustules, brown macules, and brown crusts were appreciated on bilateral palms and soles. No mucous membrane or nail involvement was noted.
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CASE #1: Erythema annulare centrifugum
Erythema represents a change in skin color that may vary from pink to red to violaceous. The color changes arise from the dilation of blood vessels located in the papillary and reticular dermis and may last anywhere from minutes to days to months. Erythema may be caused by trauma, changes in temperature, and various skin diseases.1 The four major types of erythemas are diffuse, regional/localized, reticulated, and figurate. Annular, arciform, or polycyclic lesions are used to describe figurate erythemas. Erythema annulare centrifugum (EAC) is one such figurate erythema. The other disorders in this category include erythema marginatum, erythema migrans, and erythema gyratum repens.
EAC was first described as pruritic, persistent, ring-shaped lesions and was named erythema gyratum perstans in 1881 by Colcott-Fox.2 It would be almost three decades until Wende gave a different description of recurrent lesions with scaly crust, which he called erythema figuratum perstans. Darier finally came up with the current name of EAC in 1916.2 He described the condition clinically as an annular or arcuate erythematous eruption with or without scaling.
Although EAC may happen at any time in life, its peak incidence is during the fifth decade. The disease does not discriminate by sex or race. EAC occurs in approximately one out of every 100,000 people.2 Although the precise pathogenesis is still unknown to scientists, EAC is thought to be a hypersensitivity reaction to many different antigens. Dermatophytes are presumed the most likely cause, along with other fungi, parasites, ectoparasites, viruses, foods, and drugs.2,3 Graves disease, HIV, autoimmune hepatitis, and chronic lymphocytic leukemia are also potential causes.4 The mechanism of disease is still under investigation. Current theory proposes that tumor necrosis factor-alpha and interleukin-2 may have a role in the pathogenesis of the disease, given the disappearance of the lesions after administration of interferon (Intron, Roferon).5
The initial lesions of both variants of EAC (superficial and deep) tend to be single or multiple erythematous, edematous papules that are located in greatest concentrations on the thighs, buttocks, and trunk. The lesions begin as pink papules that migrate centrifugally and clear centrally. The rings extend approximately 1 mm to 3 mm per day; however, some lesions have been known to enlarge to approximately 6 cm within one to two weeks.6 The lesions are usually asymptomatic but may occasionally be associated with pruritus, especially if spongiosis is present in the histologic examination of the biopsy. The expansion may not be uniform, and the ring will break and form arcs and polycyclic lesions. The lesions will become slightly elevated and an apparent trailing scale will form. The scale is the desquamation of the inner margin. Deep EAC is more infiltrative and does not usually have pruritus or trailing scale. Lesions are usually generalized or localized and rarely spread to involve the soles, hands, mucous membranes, and scalp. Lesions may be present for weeks to months.1,6 When EAC is associated with an underlying disorder, flares of the disorder may cause recurrences of EAC.
The histology differs between the two variants of EAC. Superficial EAC has focal parakeratosis and spongiosis. In the superficial dermis, there is a tight perivascular lymphocytic infiltrate surrounding dilated vessels, often referred to as a coat-sleeve anomaly.2 Eosinophils are rarely seen. The epidermis is usually uninvolved in the deep variant, and the perivascular coat-sleeve infiltrate favors the mid and lower dermis.
EAC must be annular, arciform, or polycyclic. If this arrangement is not present, EAC can be ruled out. EAC is often misdiagnosed, primarily because it may look like other erythematous annular diseases. Other diseases commonly mistaken for EAC include other gyrate erythemas, tinea corporis, annular urticaria, annular pustular psoriasis, lymphoma cutis, and erythema multiforme. Such autoimmune disorders as linear immunoglobin (Ig) A bullous dermatosis, Sjögren syndrome, and lupus erythematous can also have an appearance similar to that of EAC.
Once a diagnosis of EAC is made, remember to obtain a thorough history and specific blood tests to determine if the cause is idiopathic or attributable to an underlying disorder. Underlying disorders must be treated and may lead to resolution of the skin disease. Topical corticosteroids may provide some benefit if applied to the advancing border of the lesion. Systemic corticosteroids often lead to complete resolution; however recurrences are common after the medication is discontinued. If pruritus is present, incorporate topical antipruritics and sedating antihistamines into the treatment plan.2 Some have advocated the empiric use of antibiotics or antifungals, even in the absence of an identifiable cause.2
The outlook for patients with EAC is excellent. Fortunately, there is no residual scarring. However, there may be some associated postinflammatory hyperpigmentation or purpura.
In this patient, a 4-mm punch biopsy was obtained and confirmed the diagnosis of superficial EAC, showing parakeratosis, spongiosis and a superficial coat-sleeve pattern of inflammation. No underlying disorder was ever identified. Given that the lesions were pruritic, they were treated with triamcinolone 0.1% ointment b.i.d. and hydroxyzine as needed. The lesions resolved within two months, and the patient has had no recurrences to date.
CASE #2: Pustular psoriasis
Pustular psoriasis is an uncommon disease that affects individuals from all racial backgrounds. Some studies done in Asian countries show that only 7.5 individuals per 1,000,000 are diagnosed with pustular psoriasis. In adults, both sexes are affected equally; in children, boys may be affected slightly more often than girls. The average age of onset is 50 years, but there have been nearly 300 documented cases in infants as young as age one week.1,7 Pustular psoriasis is an unusual variant of psoriasis that has many possible triggers, including pregnancy, rapid tapering of corticosteroids or other systemic therapies, hypocalcemia, infections, and local irritants.
The condition can be divided into generalized pustular psoriasis, acrodermatitis continua of Hallopeau, and pustulosis of the palms and soles. Baker and Ryan have proposed four different subcategorized patterns of generalized pustular psoriasis.2 These patterns include von Zumbusch, annular, exanthematic type, and localized.2,8 During the course of the disease, the lesions may transition from one pustular variant to another and even into other manifestations of psoriasis. The onset is fairly rapid and progresses quickly. The skin located in the flexures, genital regions, webs of the fingers, and periungual areas are most commonly affected.1
In the von Zumbusch pattern, the skin may become painful and begin to develop sheets of erythema and pustulation. The patient is often ill and suffers from a fever. After several days, the pustules usually resolve and extensive desquamation and brown crusting in areas of the previous pustules may be observed.
The annular pattern is seen in up to 60% of children who are affected by pustular psoriasis.1 This pattern is characterized by annular inflammatory plaques that are studded with pustules that range from 2 mm to 3 mm in diameter.1 The plaque will enlarge centrifugally over hours to days, leaving behind desquamation as it heals. Patients may complain of fever, pain and general malaise.
An acute eruption of small pustules is characteristic of the exanthematic type. This variant usually follows an infection or is the result of administration of specific medications, most notably lithium (Eskalith, Lithobid). Systemic symptoms are rare.
In the localized pattern, pustules appear within or at the edge of pre-existing psoriatic plaques. This is often seen after the application or irritants such as tar. Impetigo herpetiformis is likely a manifestation of generalized pustular psoriasis during pregnancy and may be triggered by hypocalcemia. Lesions in mucous regions are also common, often affecting the mouth and tongue.1 The disease is cyclic and is associated with relapses that are common and become progressively more severe.1
Acrodermatitis continua of Hallopeau is a rare manifestation of psoriasis in which pustules are seen on the distal portions of the fingers and, rarely, the toes. These pustules may scale and crust as they are healing. The nails may thicken and can even separate due to subungual lakes of purulence.
Pustulosis of the palms and soles presents with erythematous scaling plaques on the palms and soles studded with pustules and yellow-brown macules. In contrast to generalized pustular psoriasis, this disease is chronic and the pustules remain localized. Infection and stress have been identified as triggering factors while smoking may aggravate the course. Rarely, pustulosis of the palms and soles may be associated with SAPHO syndrome. Seen in several neutrophilic dermatoses, SAPHO syndrome consists of synovitis, acne, pustulosis, hyperostosis, and osteitis.
Histologically, neutrophils within the stratum corneum and between keratinocytes are a characteristic feature of pustular psoriasis. Exaggerated microabscesses of Munro and spongiform pustules of Kogoj, the hallmarks of active psoriasis, are seen normally in pustular psoriasis.6,9 Microabscesses of Munro are described as the accumulation of neutrophil remnants in the stratum corneum, surrounded by parakeratosis. Spongiform pustules of Kogoj are described as the accumulation of neutrophils within a spongiotic pustule.
Some disorders that may be mistaken for pustular psoriasis include impetigo, superficial candidiasis, dermatophyte infection, pemphigus foliaceus, immunoglobulin A pemphigus, Sneddon-Wilkinson disease, EAC, contact dermatitis, acute generalized exanthematous pustulosis, and extensive bacterial folliculitis.2,10 In infants, transient neonatal pustular melanosis and acropustulosis of infancy must be considered. Differentiation from infectious causes may be resolved using viral, bacterial, and fungal cultures. A KOH examination may help to exclude a dermatophyte infection. Acute generalized exanthematous pustulosis is a pustular drug eruption, and a thorough history may help to elicit the offending drug. Eosinophils will often be seen during histologic examination, which may also help to differentiate between the two disorders. For other etiologies, a biopsy may be needed to determine the definitive diagnosis.
Acitretin (Soriatane) has proved to be the most effective monotherapy in those with pustular psoriasis. The dose should be maximized to up to 1 mg/kg/day. The endpoint that is desired is a dosage that causes a cheilitis that is still tolerable.2 Much consideration should be given before starting a woman of childbearing age on acitretin given the teratogenicity. A woman of childbearing age placed on acitretin is required to be on two forms of birth control for one month prior to treatment, during treatment, and for three years after treatment (given the potential half-life). During treatment, the clinician must monitor the woman’s pregnancy status, cholesterol and triglycerides, serum creatinine, and liver function.2 An x-ray of the spine should be done yearly to monitor for the development of hyperostoses.2 Other more conservative treatments include vitamin D3 analogues, corticosteroids, and photo- or chemotherapy.
Case studies have shown patient prognosis to vary from excellent to poor. Complications can cause much patient distress. Bacterial skin infections, hair loss, and nail loss are some of the most common complications a patient may experience. The open pustules may lead to secondary bacterial infection or septicemia. Other complications include hypocalcemia, renal tubular necrosis, liver damage, and malabsorption. The von Zumbusch type of pustular psoriasis may cause death (heart and lung failure) if it is not treated in the acute phase. Older patients usually have a less favorable outcome. However, children diagnosed with pustular psoriasis tend to do well.2
This patient was diagnosed with pustulosis of the palms and soles. Treatment with acitretin led to a complete resolution of his disease.
Kerri Robbins, MD, is a resident in the Department of Dermatology at Baylor College of Medicine in Houston.
- Paller AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology. 3rd ed. Philadelphia, Pa.: Elsevier Saunders; 2006:89-91, 541-542.
- Bolognia JL, Jorizzo JL, Rapini RP, eds. Dermatology. 2nd ed. St. Louis, Mo.: Elsevier-Mosby; 2008: 126-127, 277-281.
- Furue M, Akasu R, Ohtake N, Tamaki K. Erythema annulare centrifugum induced by molluscum contagiosum. Br J Dermatol. 1993;129:646-647.
- Gulati S, Mathur P, Saini D, et al. Erythema annulare centrifugum with autoimmune hepatitis. Indian J Pediatr. 2004;71:541-542.
- Auquier-Dunant A, Mockenhaupt M, Naldi L, et al. Correlations between clinical patterns and causes of erythema multiforme majus, Stevens-Johnson syndrome, and toxic epidermal necrolysis: results of an international prospective study. Arch Dermatol. 2002;138:1019-1024. Available at archderm.jamanetwork.com/article.aspx?articleid=478935.
- Elder DE, Elenitsas R, Johnson BL, et al, eds. Lever’s Histopathology of the Skin. 10th ed. Philadelphia, Pa.: Lippincott Williams & Wilkins; 2009:171-172, 178.
- Ivker RA, Grin-Jorgensen CM, Vega VK, et al. Infantile generalized pustular psoriasis associated with lytic lesions of the bone. Pediatr Dermatol. 1993;10:277-382.
- Fitzpatrick TB, Johnson RA, Wolff K, Suurmond R, eds. Color Atlas and Synopsis of Clinical Dermatology, 5th ed. New York, N.Y.: McGraw-Hill; 2005:64-67.
- RP Rapini. Practical Dermatopathology. Philadelphia, Pa.: Elsevier Mosby; 2005:51-52, 63-64.
- Habif TP. Skin Disease: Diagnosis and Treatment. 2nd ed., Philadelphia, Pa.: Elsevier Mosby; 2005:108-111.
All electronic documents accessed July 15, 2012.