Erythema Annulare Centrifugum Clinical Presentation

Usually, patients with erythema annulare centrifugum (EAC) present with an asymptomatic or pruritic eruption of variable duration. The eruption may be associated with an underlying disease (eg, infection, malignancy, sarcoidosis, other systemic illness) and its accompanying characteristic symptoms (eg, night sweats, fever, and chills for tuberculosis or Hodgkin lymphoma).^[8]

EAC may precede malignancy by 2 years or more, but it can also occur concomitantly or after diagnosis.

The temporal relationship to other underlying diseases, if any, is also variable. Obtain a history of any antecedent infections.

A history of recent initiation of a new drug should be ascertained because many reports of medication-associated erythema annulare centrifugum exist (most commonly antimalarials, cimetidine, spironolactone, gold, salicylates, piroxicam, penicillin, and amitriptyline).

One case report^[9] has described EAC as a manifestation of autoimmune progesterone dermatitis in a female with a recurring annular pruritic eruption. She experienced monthly exacerbations of the eruption a few days prior to onset of menses. A similar hormonal etiology has been reported in the case of a woman who developed EAC in the 33rd week of pregnancy.^[10] The eruption resolved 1 month after delivery, without recurrence after 8 months of follow-up.

Pertinent physical findings of erythema annulare centrifugum (EAC) are usually limited to the skin, but a full physical examination should be conducted to assess for an underlying systemic process.

Skin findings are as follows:

• Primary lesion: The eruption begins as erythematous papules that spread peripherally while clearing centrally. These lesions enlarge at a rate of approximately 2-5 mm/d to produce annular, arcuate, figurate, circinate, or polycyclic plaques, as shown in the images below. The margin, which is usually indurated, varies in width from 4-6 mm, and, often, a trailing scale is present on the inner aspect of the advancing edge. The diameter of the polycyclic lesions varies from a few to several centimeters. Vesiculation may be present. Note the images below. Arcuate lesions of erythema annulare centrifugum demonstrate minimal scale. Superficial erythema annulare centrifugum demonstrates a central clearing and trailing scale behind an advancing, annular, erythematous border.
• Distribution: Lesions demonstrate a predilection for the thighs and the legs, but they may occur on the upper extremities, the trunk, or the face. The palms and the soles are spared.
• Color: The lesions are pink to red with central clear areas. Occasionally, residual hyperpigmentation of dull red, brown, or violet is present. A case of EAC associated with hyperbilirubinemia and jaundice secondary to choledocholithiasis has been reported.

Other findings are as follows:

• Nails: White banding of the toenails has been reported in association with EAC.
• Lymph nodes: Lymphadenopathy may be present in cases of EAC associated with Hodgkin or non-Hodgkin lymphoma, tuberculosis, or autoimmune processes.
• Neck: The thyroid should be palpated for enlargement or nodules because Graves disease has been associated with EAC.^[4]
• Lungs: Tuberculosis,^[11] lymphoma, sarcoidosis, and malignant bronchial carcinoid have been associated with EAC, warranting examination of the lungs.
• Abdomen: Appendicitis,^[6] lymphoma (with associated splenomegaly), and liver disease^[3] (eg, cholelithiasis, hepatitis), and pregnancy have been reported with EAC. The abdomen should be examined for tenderness, masses, or hepatosplenomegaly.

Most commonly, no cause is found for the erythema annulare centrifugum (EAC).^[12] However, the literature contains numerous case reports documenting association with other diseases. Often, the eruption of EAC resolves after treatment of the underlying illness.

Infections

Infection-related causes include the following:

• Bacteria: Associations include Escherichia coli. One case associated EAC with a urinary tract infection that cleared 3 weeks after treatment of the urinary tract infection.^[13] Other associated bacterial infections include streptococcal infections (eg, bacterial meningitis.
• Fungi: Dermatophytes (Trichophyton, tinea pedis, Pityrosporum orbiculare/Malassezia furfur) are associated, as is Candida albicans and blue cheese Penicillium.
• Mycobacteria: Mycobacterium tuberculosis is associated. Treatment with isoniazid, rifampin, and streptomycin cleared the eruption of EAC within 20 day of starting therapy for tuberculosis in a patient.
• Parasites: These include Ascaris lumbricoides^[14] ; EAC resolved after treatment with piperazine and thiabendazole. Also, EAC has been reported in association with Phthirus pubis infestation.^[15]
• Viruses: EAC has been reported in association with Epstein-Barr virus (EBV) in an infant^[16] and with molluscum contagiosum in an 8-year-old child. In the infant, the appearance and subsequent resolution of the eruption coincided with the patient's anti-EBV antibody titer, supporting EBV as the inciting agent. In addition, the viral genome has been found in the DNA of Reed-Sternberg cells in patients with Hodgkin disease and in patients with nasopharyngeal carcinoma. Both of these neoplasms have been associated with EAC. Two cases of EAC were reported in a dermatomal distribution within the exact distributions of recent prior herpes zoster infections. These cases were cited as examples of "Wolf's isotopic response."^[17] In 2006, erythema annulare centrifugum (EAC) was reported in an HIV-positive patient.^[18]

Drugs

In each of the following cases, the eruption of EAC appeared after initiation of the drug and resolved after its cessation. In the cases of the antimalarials chloroquine and hydroxychloroquine, the eruptions took 5 months to a year to clear, believed to be secondary to their strong DNA-binding properties and affinity for melanin. Note the following:

• Finasteride
• Chloroquine
• Hydroxychloroquine^[19]
• Estrogen
• Cimetidine
• Penicillin
• Salicylates
• Piroxicam
• Hydrochlorothiazide
• Gold sodium thiomalate
• Amitriptyline^[20]
• Etizolam^[21]

Neoplasms

In each of the following cases, EAC resolved with successful treatment of the malignancy but relapsed with tumor recurrence in the cases of Hodgkin disease, acute myelogenous leukemia (AML), and squamous cell carcinoma in a sebaceous cyst. However, in the latter case, EAC cleared in the terminal stage of the disease. This was purported to be due to immune compromise with tumor progression. Note the following:

• Squamous cell carcinoma (in a sebaceous cyst)
• Nasopharyngeal carcinoma
• Acute myelogenous leukemia
• Peritoneal carcinomatosis
• Primary bronchial carcinoid^[22]
• Hodgkin lymphoma^{[23, 24]}
• Chronic lymphocytic leukemia
• Multiple myeloma
• Prostate cancer
• Malignant histiocytosis
• Ovarian carcinoma (mucinous)
• Breast cancer^[25]

Other causes

Other reported causes vary and include the following:

• Foods: Blue cheese and tomatoes have been reported to cause EAC
• Recurrent acute appendicitis: The lesions of EAC resolved 1 month after appendectomy.^[6]
• Cholestatic liver disease (secondary to choledocholithiasis): EAC resolved within 3 days of removal of the stone.^[3]
• Graves disease: The patient's eruption disappeared 2 weeks after treatment with I-131 for thyroid ablation.^[4]
• Menstruation: A case has been reported of a woman with EAC whose lesions stopped progressing premenstrually and enlarged again with the onset of menses. Another patient experienced exacerbations of EAC premenstrually as a type of autoimmune progesterone dermatitis.^[9]
• Hypereosinophilic syndrome: A patient with 31% eosinophilia (with no underlying cause found), pruritus, and EAC was treated with ketoconazole, dapsone, and trimethoprim-sulfamethoxazole with resolution of the eruption occurring after 2 weeks.^[5]
• Sjögren syndrome
• Sarcoidosis: EAC was reported in association with underlying systemic sarcoidosis.
• Osteoarthritis: A 73-year-old man with an 11-week history of EAC that was associated with the onset of left knee osteoarthritis received injections of intra-articular hyaluronic acid that effected resolution of both his osteoarthritis and the EAC.^[26]
• Stress: One report describes stress as an inciting factor in one case of EAC. The patient experienced EAC at the onset of stressful life periods, which abated without treatment upon discontinuation of the stressful period in the patient’s life.^[27]
• Pregnancy: One case report describes the onset of EAC during pregnancy, with resolution occurring shortly before delivery.^[28]