Review
THE ANNULAR ERYTHEMAS PHILIP V. HARRISON, M.R.C.P.
From the Department of Dermatology, Royal Victoria Inlirmary, Newcastle upon Tyne, England
The annular or figurate erythemas are uncomti"ion forms of toxic erythema whose classification has been made difficult by many descriptive terms. The annular erythemas are cutaneous eruptions characterized by circinate, arcuate and polycyclic lesions which may be fixed or migratory.'
Classification Many descriptive terms have been used (Table 1) which have arisen due to minor variations in thp morphology and clinical behavior of Ihe conditions.^ Many of these re|)resent different terminologies for a similar eruption although some have emerged as distinct entities as discussed later. SumtiTerly^ grouped these c o n d i t i o n s under the heading of tigurate erythema and White and Perry"* used the term erythema [jerstans. Other authors have tended to subdivide and probably the first attempt at classification was made by Tachau in 1928.^
1. Erythema chronicum migrans 2. Erythema annulare cenlrifugum 3. Erythema microgyratum perstans 4. Erythetina simplex gyratum In 1964 Shelley" simplified the classification and this was later used by Thivolet and colleagues:^ 1. Erythema chronicum migrans (ECM) 2. Erythema annulare centrilugum [EAC) 3. Erythema gyratum ret>ens (EGR) Much of the available evidence suggests that this classification most closely corresponds with the majority of clinical observations and is based on the etiology, morphology and clinical behavior of the conditions. Before these are discussed in detail, two olher disorders merit description. Erythema Marginatum Rheumaticum This annular erythema may be separated from the others classified above by its known association with rheumatic fever and characteristic clinical picture, with rapid onset and S|)read.** Whereas it used to be fairly common and occurred in up to 10% of patients with rheumatic fever, it is now only rarely seen because of the diminished incidence of this intection. Erythema Dyschromicum Perstans (EDP) Ramire7 in 1957" tirsi [^resented cases of EDP under Ihe title dermatosis cenicienta (ash-colored dermatosis).
Address tor reprinis: Dr. Philip Harrison, Department ol Dermatology, The General Infirmary, Great Cieorge Street. Leeds, LSI 3EX. England.
001 l-9O59/79/050O/O282/$OO.95 © international Society of Tropical Dermatology, Inc.
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Table 1. History of the Annular Erythemas* Date
Author
1881 1901 1903 1906 1908 1909
Fox Sachs Finny Wende Wende Afzelius
1913 1916 1922 1928 1948 1952
Lipschutz I Darier Strempet ladassohn Gammel Gammel
Title Erythema Erythema Erylhema Erythema Erythema
gyratum perstans exudalivum perstans marginatum perstans perstans figuratum perstans
' Erythema chronicum migrans Erythema Erythema Erylhema Erythema Erythema
" Adapted from reference 2.
In 1961, Convitt and colleagues^" proposed the term erythema dyschromicum perstans and in 1966, Stevenson and Miura'^ placed the condition in the annular erythema group of disorders. However, Knox et al. in 1968'^ separated EDP, morphologically and histologically from EAC and other annular erythemas. Clinical Features, Histology and Causes The trunk is atfected wilh erythematous maculesof varying size which are not usually indurated, and gradually become slate-grey colored.'^•'"' The differential diagnosis includes pityriasis rosea, urticaria i^igmentosa, incontinentia pigtnenti, lichen [jlanus, lupus erythematosus and fixed drug eruption.''' The histologic changes include liquefaction degeneration of epidermal basal cells, a mild to moderate dermal perivascular Infiltrate with mononuclear cells and incontinence of pigment with associated melanophages.^"''^-'^ Soter and colleagues"* described the electron microscopic changes and Pitikus'' discussed the pathogenesis with reference to basal cell damage. The cause is obscure although racial factors may be important since the condition has
Fig. I. Two lesions on a patient's arm showing erylhema chronicum migrans. Artist's rendering of original drawing from Sonck,^' 36.
annulare centrifugum microgyratum perstans simplex gyratum gyralum migrans gyratum repens
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been mainly described in the peoples of Latin America.'^ However, there have been occasional reports in fair-skinned individuals.'"•''** The Annular Erythemas
Erythema Chronicum Migrans (ECM) This was first mentioned in 1909'^ and more fully described In 1913 by Llpschutz.^" Clinical features and histology. The condition is characterized by an expanding, erythematous band around a tick (usually genus Ixodes) or mosquito bite and the lesions are single or more rarely multi[jle.^' Figure 1 shows two lesions on the arm of a patient. There may be an associated meningitis and other constitutional symptoms,^''"^'' although some believe the meningitis is coincidental and due to a tick-bone encephalitis virus.^' ECM is usually seen in Europe, although it has been described in North America^^-^^ and the histologic features are similar to those seen in EAC. Pathogenesis and treatment. It has been suggested that an Infective agent (viral, rickettsial or bacterial) is introduced into the skin with the bite and some patietits have a positive Weil-Felix reaction indicative of rickettsial infection.'•^'^ Of interest, ECM has been occasionally observed around moUuscum contagiosum lesions^^ which may indicate a viral i>,duse in some palients. An infective cause is supported by the improvement usually obtained with penicillin or other antibiotics, such as tetracycline and erythromycin.^^ Erythema Annular Centrifugum (EAC) Histology and terminology (Table 1). In 1881, T. C. Fox^" described an annular eruption in a brother and sister which he termed erythema gyratum perstans. He felt ihere were similarities with erythema multiforme, although the absence of constitutional symptoms differentiated it from this condition.
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Wende, in 1906,^' introduced the term erythema perstans on the basis of two |)atients and later, in 1908, used the lerm erythema figuratum perstans fora similar eruption.^^ He discussed other descriptions of annular erythema and, like Fox, felt the condition was separable trom erythetna multiforme. In 1916, Darier published his description of EAC^^ although he had originally seen the patient in 1898. He discussed other reports of annulare erythema, including those of Fox and Wende, and felt that although Fox's patient was similar, other patients may have had variants ot dermatitis herpetiformis. He came to the conclusion that EAC was distinctive and one of his differentiating features between it and erythema tlguratum perstans, was the absence of vesicles in the former and their presence in the latter. Later, both Butler^^ and Klaber^^ discussed the relationship between EAC and other annular erythemas. They separated EAC from erythema gyratum perstans, erythema perstans and erythema figuratum perstans, although the evidence for this was not convincing. Klaber^^ separated EAC from dermatitis herpetiformis with which some authors had confused the condition. He also emphasized the occurrence of erythema gyratum perstans in young adults and children. However, EAC has been described as occurring in infancy,^^ and Gianotti and Ermicova^^ described an annular eruption in an infant which they maintained was different from previously described conditions, but it was probably a variant of EAC. Goltz' separated erythetna gyratum perstans from EAC by the familial occurrence of Ihe former and this is discussed by Beare and colleagues^** who described annular erythema in an Irish family. However, the justification tor this separation is doubtful. Thivolet' was ot the O[)inion that EAC (Darier) resembled erythema gyralum perstans (Eox) and erythema figuratum perstans (Wende) and all these conditions
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Fig. 2. Erythema annulare centrilugum. Interval of 10 days between condition A and B. Artist's rendering of original drawing from page 61.
should be grouped under one heading. EAC is Ihe term usually used and includes all Ihe conditions described in Table 1, with the exceplion of ECM and EGR. Clinical features. These have been well described ^^^^'^ and consist of erythematous, annular bands which may spread outwards or remain stationary. Various gyrate forms have also been documented. The edges of lesions may be elevated and tirm and are usually shar|)iy demarcated from the surrounding skin. Slight scaling or vesicles may be present along the edges, although in Darier's original description^-'' vesicles were absent. A bullous variant has been described but this is uncommon.^^•'•" The extent of the eruption is variable and the trunk is usually affected, changes being less marked on the limbs. The scalp may have a nonspecific scaly appearance and the hands, feet and face are usually spared. Itching is common but other constitutional symptoms are usually absenl. Figure 2 is adapted from Darier's original description of EAC. Histology. The histotogic changes predom-
inantly aftect the dermis, and a w e l l demarcated perivascular intiltrate of tiiononuclear cells is the main feature, the epidermis being essentially normal. The histology is distinct I'rom discoid lupus erythematosus, secondary syfihilis, leukemia cutis and erythema multiforme.^" Causes. EAC has been attributed to many etiologic factors as shown in Table 2. The idea thai some cases are secondary lo tungus infections has both experimental and clinical evidence.•'^•^''••"* Regarding a drug etiology, Ashurst""^ described ihree patienls with EAC possibly due to
Table 2. Causes of Erythema Annulare Centrifugum Viral infection*' Candida I ungus Mould li\persensitivily* Drugs (chloroqume)" Lu|)us erythematosus'"' BreasI hypertrophy*' Malignancy^'•"*"'•'
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Table 3.
Differential Diagnosis of Erythema Annulare
Tinea corporjs Granuloma annulare Annular sarcoid Erythema multiforme Drug eruption Urticaria Discoid lupus erythematosus Facial granuloma Annular psoriasis Seborrhoeic dermatitis Benign lymphocytJc infiltration Lymphoma Premycotic mycosis fungoides
chloroquine and this is further discussed by Rekant and Becker*" who felt that some cases of EAC were variants of lupus erythematosus. To substantiate this hypothesis, they present a patient with annular erythema and a high titer of antinuclear antibody, although she had normal double stranded DNA binding and negative cutaneous immunoflourescence. Bo'nniger and Hapi^le''^ reviewed the association of EAC and malignancy including leukemia, reticulosis and carcinoma. How-
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ever, White and Perry,'* in a study of 113 patients with annular erythema, found no increased Incidence of malignancy or tinea infection, The relationship between EAC and malignancy is discussed again later. Differential diagnosis. Many conditions have been confused with EAC (Table 3), but they can usually be distinguished without difficulty. Pustular psoriasis may occasionally be annular In form and thereby mistaken tor f^(;^35,54.55 although they may be distinguished tnorphologically and histologically.^^ Oneimportant feature is the rarity of lesions on the palms and soles of patients with annular erythema,"* whereas such lesions are common in patients with psoriasis. Erythema Cyratum Repens (ECR) Repens—Latin, participle from repo: to crawlorcreep. EGRwasfirstdescribedin 1952 by Gammel2 in a 56-year-old woman with carcinoma ofthe breast. He reviewed the literature on the cutat"ieous manifestations of internal malignancy and concluded that EGR was
Fig. 3. Erythema gyratum repens. Artist's rendering of original photograph from Gammel,^ page 497.
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dislinctive and also different from EAC and other annular erythemas. Clinical features and histology. There is a generalized eruption with parallel bands of erythema in an annularorgyratearrangement. It may resemble grains of wood and have a zebra-like appearance,^ although in the early stages the rash may resemble pityriasis rubra pilaris. Scaling is usually more tnarked in EGR than in EAC, which may be due to the more rapid movement ofthe former, which changes configuration daily, whereas EAC moves more slowly over a period of weeks.^^ Pevny^^ presented a list of differentiating features between EAC and EGR and in Gammel's original description of EGR,^ the keloid consistency of EAC was absent. Like EAC, there is relative sparing of the hands, feet and face and there are nonspecific changes on the scalp in EGR. Itching occurs although probably less marked than in EAC 2'^*''^" According to Pevny^" there are histoiogic differences between EGR and EAC, although other investigators were not convinced.^''^*^** Eigure 3 is adapted frotii Gammei's original description of EGR. Assoc/a(/on wilh malignancy. Although the condition is usually associated with malignancy (25 out of 26 reports) it has also been described wilh [Hilmonary tuberculosis.^^ Skolnick and Mainr"nan'"* reviewed 21 patients with EGR and malignancy although there have been others,^'"^^ including a 75year-old man with pulmonary carcinoma brought to ihe author's attention.""* Table 4 summarizes these 25 patients wilh EGR and malignancy. Ninety-two percent of patients had a carcinoma including lung, alimentary tract, urogenital tract and breast; the lung being involved in 44% of the cases, most of whon"i were men. The rash usually preceded the discovery of malignancy""-"-* and this phenomenon was first described by Gammel.^ Also, he first rec-
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Harrison Table 4. Erylhema Cyratum Repens and
Carcinoma of lung Carcinoma of uterus or cervix Carcinoma of breast Carcinoma ot stomach Carcinoma of anus Carcinoma of tongue Carcinoma of hypopharynx Carcinoma of bladder Carcinoma ot proslate Multiple myeloma Malignant melanoma Tola I
Average Age
1 1 patients (10 men, 1 sex unspecifiedl 3 patienls 2 patients (women) 2 patienls (1 man, I woman) 1 patient (woman) 1 patient (man) 1 patieni (man) 1 patieni (woman) 1 patient 1 patient (woman) 1 patient (man) 25 patienls (1 5 men, 9 women, 1 sex uns|jecified) 60 in those In which age specified
ogni/ed ihe improvement in the rash after treatment of the malignancy. Many patients experience some improvement, which varies Irom moderate to dramatic depending on the susceptibility of the malignancy to therapy. Discussion
Erylhema marginatum rheumaticum, associated with rheumatic fever, and erythema dyschronicum perstans are distinct and separate entities. ECM is recognized by its association with a tick or mosquito bite, usual occurrence in Euro|K', possibly associated meningitis and other constitutional symptoms, and the response to antibiotics. EAC may be distinguished from EGR as shown in Table 5. It Is doubtfiil whet her EAC is associated with malignancy and, although Bonniger and Happle^-'' and Pevny^^ described an association. White and Perry,"* after studying a large groupof patients with annu lar erythema, were unconvinced. However, the association of EGR with malignancy isestablished and the rash in most
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Table 5. Comparison Between Erylhema Annulare Centrifugum (EACi and Erythema Gyratum Repens (EGR) EAC
Association wilh malignancy Association with other diseases
EGR
Rarely Intections, drugs, breast hypertrophy, lupus erylhemalosus Annular conliguration of rash is variable
Clinical features
Scaling slight
Movement ot rash
May be induraled itching moderate Slowly over weeks
Yes, usually pulmonary carcinoma in men Tuberculosis
Characteristic appearance, like grains of wood Scaling, sometimes marked Not indurated Itching slighl Rapidly over days
Table adapted from various sources, including reference 56.
[lalietits has a characteristic appearance. The presence ol FGRshoukI |)rom|)t a search tor an underlying malignaticy, especially pulmonary in men. If no malignancy is found, the patient should be kept utider review atxl invesligalions repeated, since in some [)alients the rash has preceded the malignancy by n"iany months."" An indicalion for radiologic itivestigations in EGR contrasts with some other sklti tliseases, such as bullous |>em|.)higoid, where the case tor such investigations is unconvincing.''^' Lackot malignancy should not [irevetit a search for other causes of EGR si nee it has been described with [itilnionary tuberc"Lil()sis.^'^ ThetherapyofEACand EGR is limited (Table bland most improvement, especially in EGR, is obtained by treatmenl of the underlying cause, it this is known.
Table 6. 1. 2. 3. 4. 5.
Ireatnieni »i tAC and ECR
Treatment ot underlying condition. AntJhistamine-', Topical sleroids. Systemic steroids. AntJmetabolites.
Table adapted from various sources.
The clinical appearance and [jalhogenesis ol the annular erythemas are misunderstood and EAC and EGR may rei^resent similar reaction palterns to a stimLilus, one Lisually nonmalignant and the other malignanl. EAC and EGR can be louncl in the same patieni at different times,"" EAC develo|)ing betore tieo|ilasia was n"ianifest, although later FGR developed. Van Dijk"^ presetited a woman with uteritie carcinoma who had I'eatures of EAC and EGR [ireset"il simulUineously. Gammel^ discussed theories explaining the spreading nature of EGR and Becker etal.,'*^ in a discussion of EAC, felt that when associated with malignancy, there was a direct infiltration ofthe skin with malignant cells, although this would no longer be accepted. Lazar''" described EAC with tumor cells in the skin causing an immune reaction and interest in the immunology of the annu lar erythemas was stimulated by Shelley's description of a patient with EAC and massive breast hy[)ertrophy."*^ Circulating anti bodies to breast tissue with a positive LE phenon"ienon were present and the EAC disappeared alter surgical reduction of breast size. Itnmunologic mechanisms n"iay have been involved in a patient with EGR and pulmonary
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carcinoma."^ The various possibilities included: 1. Antibodies produced against tumor antigens cross-reacting wilh cutat"ieous antigens. 2. Tumor polypeptides acting as culaneous haptogens. 3. Circulating immune complexes. A similar patient with EGR and pulmonary carcinoma recently came to the author's attention."^ The immunofluorescence of involved skin resembled that reported by Holt and Davies,"''' with granular deposits of IgG and C.j in the basement membrane zone. The patient had elevated levels of carcinoembryonic antigen which may have participated In the pathogenesis of the rash. More immunologic studies ot the annuLir erythemas are required and are only hindered by the rarily of these conditions. Conclusions 1. The annular erythemas inclticle erythema chronicum migrans (ECM), erythema annulare cenlrifugum (EAC) and erythema gyratum repens (EGR). 2. ECM is associated with tick or mosquito bites, occurs mainly in Europe and responds well to antibiotics, especially penicillin. 3. EAC includes most of the other terms used for the annu lar erythemas. There are various etiologies but it israrely, ifat all associated with malignancy. It may bedislinguished from EGR clinically. 4. EGR is almost always associaled with malignancy, especially pulmonary malignancy in men. Acknowledgments iheaulhorthanksDr. I.S.Comaishforprovidinghelpful advice, and Mr. D, P, FHammersley lor preparing the illuslrations. References 1. Goltz, R. W.: The unusual figurate erylhemas. In: Dermatology in General Medicine, Edited by Fitzpal-
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rick, T. B., Arndt, K. A., Clerk, W. H., Eisen, A. Z., Van Scott, E. I., and Vaughan, |. H., New York, McGrawHill, 1971, 2. Gammel,). A.: Erythema gyratum repens. Skin manifestation in patient with carcln(jma of breast. A.M.A. Arch, Dermatol, Syphilol. 66:494, 1952. 3. Summerly, R,: Thetigurateerythemasarid neoplasia. Br. |. Dermalol. 76:370, 1964. 4. White,|.W.,,ind Perry, H.O.: Erythema perstans. Br. ), Dermalol. 81:641, 1969. 5. Tachau, P.: Erythema exudativum multilorme und nodosum. In: Handbi;ch der FHaut-und Geschlechtskrankheilen. Berlin, |ulius Springer, 1928. 6. Shelley, W, B.: Erylhema annulare centrifugum. A case due to hypersensitivity to blue cheese penicillium. Ar(h. Dermatol. 90:54, 1964. 7. Thivolet, I., Galiois, P., and Perrot, M.: Unedermatose paraneoplasique meconnue: I'erythema giralum repens. Rev. Lyon Med. 19:789, 1970. 8. Keil, Fl.: The rheumatic erythemas, A critical survey. Ann, Intern. Med. 11:2223, 1937. 9. Ramirez, C. O.: Quoted in Stevenson, M. |. R., and Miura, M.; Erythema dyschromicum [rerslans (ashy dermalosis). Arch. Dermaloi. 94:196, 1966. 10. Convit, I., KendeUVegas, F., and Rodriguez, G.: Erythema dyschromicum perstans. A hitherto underscribed skm disease. |. Invest. Dermalol. i6:457, 1961. 1 I. Stevenson, M. |. R,, and Miura, M.: Erythema dyschromicum perstans lashv dermalosisl. Arch, Dermatol. 94:196, 1966. 12. Knox, I, M., Dodge, B. G., and Freeman, K. G,: Erythema dyschromicum perstans. Arch, Dermatol. 97:262, 1968. I.t. Fit/patrt{k,T, B,,and Mihm,M,C., |r: Abnormalities ot the melanin pigmentary system. In: Dermatology in General Medicine. Edited by Fitzpatrick, T. B., et al.. New York, 1971. 14. Hoist. R., and Mobacken, H.: Erythema dyschromicum Persians (ash dermatosisi, Acta Derm. Venereol. 54:69, 1974. 15. Lever, W. F., and S( haumburg-Lever, G,: Histopalhology of the Skin, 5th ed. Philadelphia, 1. B. Lippjncoll Co., 1975. 16. Soler, N. A., Wand, C. H. T., and Freeman, R. G.: Ultraslru< tural |>a tho logy ot erythema dyschromicum |>erst,Tns. |. Invesl. Dcrmatol. 52:155, 1969, 17. Pinkus, H.: Lichenoid tissue reactions. Arcli. Dermaloi. 107:840. 1973. 18. Byrne, D. A., and Berger, R. S.: Ervthema dyschromicum perstans. A report of Iwo cases in fairskinned patients. Acta Derm. Venereol. 54:65,1974. 19. Atzeljus, A,: Erylhema chronicum mlgr.ins, Acta Derm. Venereol. 2:120, 1921. 20. Lipschul7, B.: Uber eine seltene erythemlorm (erythema chronicum migrans). Arch. Derm. Syph. 118:349, 1913. 21. Sonck, C. E.: Erythema chronicum migrans with multiple lesions, Acta Derm, Venereol. 45:34, 1964. 22. Scrimenti, R. |.: Erylhema chronicum migrans. Arch. Dermatol. 102:104, 1970.
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2.i. Smith, L. R., Burgdorf, W., and Katz, H. 1.; Erythema chronicum migrans. Cutis 17:962, 1976 24. Hellerslrdm, S.: Erythema chronicum migrans. Afzelii. Acta Derm. Venereol. 11:315, 19)0. 25. Hellerstrbm, S.i Erythema chronicum migrans. Alzelii with meningitis. Acta Derm. Venereol. 31:227,1951. 26. Weber, K.; Erylhema chronicum migrans meningitis—eine bakterielle infeklions krankheit? Munch. Med. Wochenschr. 116:1993, 1971. 27. Putkonen, T., Mutakallio, K. K., and Salminen, A.: Erylhema chronicum migrans with meningitis. A rare coincidence of two tick borne diseases? Dermatologica 125:184. 1962. 28. Degos, P. R., Touraine, R., and Aroutle,).: L'erythema chronicum migrans. (DiscLission d' une origine rickettsienne). Ann. Dermatol. Syphiligr. 89:247, 1962. 29. Harrison, P. V.: Personal observation, 1977. 30. Eox, T. C: Erythema gyratum perstans. Trans. Clin. Soc. Lond. 14:67, 1881. 31. Wende, G. W.: Erythema perstans with report of two cases involving circinale lesions. ). Cutan. Dis. 24:241, 1906. 32. Wende, G. W.: Erylhema figuratum perstans. |AMA 51:1936, 1908. 33. Darier, J.: De' I'erylheme annulaire centrifuge. Ann. DermatoL Syphiligr. 6:57, 1916. 34. Butler, J.: Erythema annulare cenlrifugum. A.M.A. Arch. Dermatol. Syphilol. 25:111, 1932. 35. Klaber, R.: Erythema gyratum perslans (Colcott Fox). A case report with discussion on relationship with erythema annulare centrifugum (Darier) and dermatitis herpeliformis. Br.). Dermatol. 58:111,1946. 36. Ereid, R., Schonberg, 1. L, and Litt, |. Z.: Erythema annulare centrifugum (Darier) in a newborn inlant.). Pediat. 50:66, 1957. 37. Gianotti, F., anci Ermicova, E.: Erythema gyratum alrophicans transiens neonate. Arch. Dermatol. 111:615, 1975. 38. Beare.). M., Froggart. P., lones, |. H., and Neill, D. W.: Familial annularerythema. An apparently new dominant mutation. Br. |. Dermalol. 78;.S9, 1966. 39. Kind. R.: Bullose varianle des erythema annulare centrifugum Darier bei candia-albicans-infeklion. Hautarzt. 26:466. 1975. 40. Ellis. F. A., and Friedman, A. A.: Erythema annulare centrifugum (Darier's). Clinical and histologic study. A.M.A. Arch. Dermatol. Syphilol. 70:496, 1954. 41. Hammaf. H.: Erythema annulare centrifugum coincident with Epstein-Barr virus iniection in an infant. Acta Paediat. Scand. 63:788. 1974. 42. Shelley, W. B.: Erythema annulare centrifugum due to Candida aibicans. Br. |. DermatoL 77:383, 1965. 43. lillson, O. P., and Koekelman, R. A.: Further amplification of the concept of dermatophytid. A.M.A. Arch. Dermatol. Syphilol. 66:738, 1952. 44. lillson, O. F.: Allergic confirmation that some cases of erythema annuiare centrifu^um are dermalophytids. A.M.A. Arch. Dermatol. Syphilol. 70:355, 1954. 45. Ashurst, P. |.: Erythema annulare centrifugum due to hydroxychloroquine sulphate and chloroquine sulphate. Arch. Dermatol. 95:37. 1969.
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46. Rekant, S. I., and Becker. L. E.: Autoimmune annular erythema. A variant of lupus ervthematosus. Arch. Dermatol. 107:424. 1973. 47. Shelley, W. B., and Hurley. FH. |.: An unusual autoimmune syndrome. Arch. Dermatol. 81:889, 1960. 48. Becker, S. W., Kahn, D., and Rothman, S.: Cutaneous manifestations of internal malignant tumors. A.M.A. Arch. Dermatol. Syphilol. 45:1069, 1942. 49. Stillians, A.: Erythema annulare centrifugum. Its relation to internal disease. A.M.A. Arch. Dermatol. Syphilol. 67:590, 1953. 50. Lazar, P.: Cancer, erythema annulare centrifugum and autoimmunity. Arch. Dermatol. 87:246. 1963. 51. Saikia, N. K.. Mackie, R. M., and McQueen A.: A case of bullous pemphigoid and figurate erythema in association with metastatic spread of carcinoma. Br. ). Dermatol. 88:331, 1973. 52. Everall. !. D.. Dowd, P. M., and Ardalan. B.: Unusual cutaneous associations of a malignant carcinoid tumor of the bronchus—erythema annulare centrifugum and white banding of the nails. Br. |. Dermatol. 93:341. 1975. 53. Bdnniger, F., and Happle. P.: Erythema annulare centrifugum als symptom einer akuten myeloischen leukaemic. Z. Hautkr. 52:77, 1977. 54. Baker, H., and Ryan. T. ).: Generalized pustular psoriasis. A clinical and epidemiological study of 104 cases. Br. |. Dermatol. 80:771, 1968. 55. Resnick, J. S.. and Cram, D. L.: Erythema annularelike pustular psoriasis. Arch. Dermatol. 108:687, 1973. 56. Pevny, V. I.: Erythema gyratum repens. Z. Hautkr. 8:260, 1966. 57. Thomson, 1., and Stankler, L.: Erythema gyralum pens. Reports of Iwo further cases associated with carcinoma. Br. |. Dermatol. 82:406, 1970. 58. Hochleitner, H., Bartsch. G . and Zelger, |.: Erythema gyratum repens bei bronchuscarcinom. Hautarzt. 21:116. 1970. 59. Barber. P. V., Doyle, L., Vickers, D. M.. and Hubbard, H.: Erythema gyratum repens with pulmonary tuberculosis. Br. |. Dermatol. 98:465, 1978. 60. Skolnick, M., and Mainman, E. R.: Erythema gyratum repens with metastic adenocarcinoma. Arch. Dermalol. 111:227, 197S. 61. Connor, B. L.: Erythema gyralum repens. Case presentation. Trans. St. lohn's Hosp. Dermatol. Soc. 58:323, 1972. 62. Lukowska, I., and Silny, W ; Erythema gyratum repens jako schor/enie paranowotoworowe. Przegl Dermatol. 61:785, 1974. 63. Holt, P. |. A., and Davies. M. G.: Erythema gyratun repens—an immunologically mediated dermatosis' Br. |. Dermatol. 96:343, 1977. 64. Dahl, M. G. L.: Personal communication, 1976. 65. Moss, A. A., and Hanelin. L. G.: Occult malignan tumors in cfermatologic disease. The futility o radiological search. Radiology 69:123, 1977. 66. Leavell. U. W., Winternitz. W. W.. and Black. |. H. Erythema gyralum repens and unditferentiated car cinoma. Arch. Dermatol. 95:69. 1967. 67. VanDijk. E.: Erythema gyratum repens. Der matologica 123:301, 1961.
THE ANNULAR ERYTHEMAS PHILIP V. HARRISON, M.R.C.P.
From the Department of Dermatology, Royal Victoria Inlirmary, Newcastle upon Tyne, England
The annular or figurate erythemas are uncomti"ion forms of toxic erythema whose classification has been made difficult by many descriptive terms. The annular erythemas are cutaneous eruptions characterized by circinate, arcuate and polycyclic lesions which may be fixed or migratory.'
Classification Many descriptive terms have been used (Table 1) which have arisen due to minor variations in thp morphology and clinical behavior of Ihe conditions.^ Many of these re|)resent different terminologies for a similar eruption although some have emerged as distinct entities as discussed later. SumtiTerly^ grouped these c o n d i t i o n s under the heading of tigurate erythema and White and Perry"* used the term erythema [jerstans. Other authors have tended to subdivide and probably the first attempt at classification was made by Tachau in 1928.^
1. Erythema chronicum migrans 2. Erythema annulare cenlrifugum 3. Erythema microgyratum perstans 4. Erythetina simplex gyratum In 1964 Shelley" simplified the classification and this was later used by Thivolet and colleagues:^ 1. Erythema chronicum migrans (ECM) 2. Erythema annulare centrilugum [EAC) 3. Erythema gyratum ret>ens (EGR) Much of the available evidence suggests that this classification most closely corresponds with the majority of clinical observations and is based on the etiology, morphology and clinical behavior of the conditions. Before these are discussed in detail, two olher disorders merit description. Erythema Marginatum Rheumaticum This annular erythema may be separated from the others classified above by its known association with rheumatic fever and characteristic clinical picture, with rapid onset and S|)read.** Whereas it used to be fairly common and occurred in up to 10% of patients with rheumatic fever, it is now only rarely seen because of the diminished incidence of this intection. Erythema Dyschromicum Perstans (EDP) Ramire7 in 1957" tirsi [^resented cases of EDP under Ihe title dermatosis cenicienta (ash-colored dermatosis).
Address tor reprinis: Dr. Philip Harrison, Department ol Dermatology, The General Infirmary, Great Cieorge Street. Leeds, LSI 3EX. England.
001 l-9O59/79/050O/O282/$OO.95 © international Society of Tropical Dermatology, Inc.
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Table 1. History of the Annular Erythemas* Date
Author
1881 1901 1903 1906 1908 1909
Fox Sachs Finny Wende Wende Afzelius
1913 1916 1922 1928 1948 1952
Lipschutz I Darier Strempet ladassohn Gammel Gammel
Title Erythema Erythema Erylhema Erythema Erythema
gyratum perstans exudalivum perstans marginatum perstans perstans figuratum perstans
' Erythema chronicum migrans Erythema Erythema Erylhema Erythema Erythema
" Adapted from reference 2.
In 1961, Convitt and colleagues^" proposed the term erythema dyschromicum perstans and in 1966, Stevenson and Miura'^ placed the condition in the annular erythema group of disorders. However, Knox et al. in 1968'^ separated EDP, morphologically and histologically from EAC and other annular erythemas. Clinical Features, Histology and Causes The trunk is atfected wilh erythematous maculesof varying size which are not usually indurated, and gradually become slate-grey colored.'^•'"' The differential diagnosis includes pityriasis rosea, urticaria i^igmentosa, incontinentia pigtnenti, lichen [jlanus, lupus erythematosus and fixed drug eruption.''' The histologic changes include liquefaction degeneration of epidermal basal cells, a mild to moderate dermal perivascular Infiltrate with mononuclear cells and incontinence of pigment with associated melanophages.^"''^-'^ Soter and colleagues"* described the electron microscopic changes and Pitikus'' discussed the pathogenesis with reference to basal cell damage. The cause is obscure although racial factors may be important since the condition has
Fig. I. Two lesions on a patient's arm showing erylhema chronicum migrans. Artist's rendering of original drawing from Sonck,^' 36.
annulare centrifugum microgyratum perstans simplex gyratum gyralum migrans gyratum repens
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been mainly described in the peoples of Latin America.'^ However, there have been occasional reports in fair-skinned individuals.'"•''** The Annular Erythemas
Erythema Chronicum Migrans (ECM) This was first mentioned in 1909'^ and more fully described In 1913 by Llpschutz.^" Clinical features and histology. The condition is characterized by an expanding, erythematous band around a tick (usually genus Ixodes) or mosquito bite and the lesions are single or more rarely multi[jle.^' Figure 1 shows two lesions on the arm of a patient. There may be an associated meningitis and other constitutional symptoms,^''"^'' although some believe the meningitis is coincidental and due to a tick-bone encephalitis virus.^' ECM is usually seen in Europe, although it has been described in North America^^-^^ and the histologic features are similar to those seen in EAC. Pathogenesis and treatment. It has been suggested that an Infective agent (viral, rickettsial or bacterial) is introduced into the skin with the bite and some patietits have a positive Weil-Felix reaction indicative of rickettsial infection.'•^'^ Of interest, ECM has been occasionally observed around moUuscum contagiosum lesions^^ which may indicate a viral i>,duse in some palients. An infective cause is supported by the improvement usually obtained with penicillin or other antibiotics, such as tetracycline and erythromycin.^^ Erythema Annular Centrifugum (EAC) Histology and terminology (Table 1). In 1881, T. C. Fox^" described an annular eruption in a brother and sister which he termed erythema gyratum perstans. He felt ihere were similarities with erythema multiforme, although the absence of constitutional symptoms differentiated it from this condition.
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Wende, in 1906,^' introduced the term erythema perstans on the basis of two |)atients and later, in 1908, used the lerm erythema figuratum perstans fora similar eruption.^^ He discussed other descriptions of annular erythema and, like Fox, felt the condition was separable trom erythetna multiforme. In 1916, Darier published his description of EAC^^ although he had originally seen the patient in 1898. He discussed other reports of annulare erythema, including those of Fox and Wende, and felt that although Fox's patient was similar, other patients may have had variants ot dermatitis herpetiformis. He came to the conclusion that EAC was distinctive and one of his differentiating features between it and erythema tlguratum perstans, was the absence of vesicles in the former and their presence in the latter. Later, both Butler^^ and Klaber^^ discussed the relationship between EAC and other annular erythemas. They separated EAC from erythema gyratum perstans, erythema perstans and erythema figuratum perstans, although the evidence for this was not convincing. Klaber^^ separated EAC from dermatitis herpetiformis with which some authors had confused the condition. He also emphasized the occurrence of erythema gyratum perstans in young adults and children. However, EAC has been described as occurring in infancy,^^ and Gianotti and Ermicova^^ described an annular eruption in an infant which they maintained was different from previously described conditions, but it was probably a variant of EAC. Goltz' separated erythetna gyratum perstans from EAC by the familial occurrence of Ihe former and this is discussed by Beare and colleagues^** who described annular erythema in an Irish family. However, the justification tor this separation is doubtful. Thivolet' was ot the O[)inion that EAC (Darier) resembled erythema gyralum perstans (Eox) and erythema figuratum perstans (Wende) and all these conditions
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Fig. 2. Erythema annulare centrilugum. Interval of 10 days between condition A and B. Artist's rendering of original drawing from page 61.
should be grouped under one heading. EAC is Ihe term usually used and includes all Ihe conditions described in Table 1, with the exceplion of ECM and EGR. Clinical features. These have been well described ^^^^'^ and consist of erythematous, annular bands which may spread outwards or remain stationary. Various gyrate forms have also been documented. The edges of lesions may be elevated and tirm and are usually shar|)iy demarcated from the surrounding skin. Slight scaling or vesicles may be present along the edges, although in Darier's original description^-'' vesicles were absent. A bullous variant has been described but this is uncommon.^^•'•" The extent of the eruption is variable and the trunk is usually affected, changes being less marked on the limbs. The scalp may have a nonspecific scaly appearance and the hands, feet and face are usually spared. Itching is common but other constitutional symptoms are usually absenl. Figure 2 is adapted from Darier's original description of EAC. Histology. The histotogic changes predom-
inantly aftect the dermis, and a w e l l demarcated perivascular intiltrate of tiiononuclear cells is the main feature, the epidermis being essentially normal. The histology is distinct I'rom discoid lupus erythematosus, secondary syfihilis, leukemia cutis and erythema multiforme.^" Causes. EAC has been attributed to many etiologic factors as shown in Table 2. The idea thai some cases are secondary lo tungus infections has both experimental and clinical evidence.•'^•^''••"* Regarding a drug etiology, Ashurst""^ described ihree patienls with EAC possibly due to
Table 2. Causes of Erythema Annulare Centrifugum Viral infection*' Candida I ungus Mould li\persensitivily* Drugs (chloroqume)" Lu|)us erythematosus'"' BreasI hypertrophy*' Malignancy^'•"*"'•'
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Table 3.
Differential Diagnosis of Erythema Annulare
Tinea corporjs Granuloma annulare Annular sarcoid Erythema multiforme Drug eruption Urticaria Discoid lupus erythematosus Facial granuloma Annular psoriasis Seborrhoeic dermatitis Benign lymphocytJc infiltration Lymphoma Premycotic mycosis fungoides
chloroquine and this is further discussed by Rekant and Becker*" who felt that some cases of EAC were variants of lupus erythematosus. To substantiate this hypothesis, they present a patient with annular erythema and a high titer of antinuclear antibody, although she had normal double stranded DNA binding and negative cutaneous immunoflourescence. Bo'nniger and Hapi^le''^ reviewed the association of EAC and malignancy including leukemia, reticulosis and carcinoma. How-
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ever, White and Perry,'* in a study of 113 patients with annular erythema, found no increased Incidence of malignancy or tinea infection, The relationship between EAC and malignancy is discussed again later. Differential diagnosis. Many conditions have been confused with EAC (Table 3), but they can usually be distinguished without difficulty. Pustular psoriasis may occasionally be annular In form and thereby mistaken tor f^(;^35,54.55 although they may be distinguished tnorphologically and histologically.^^ Oneimportant feature is the rarity of lesions on the palms and soles of patients with annular erythema,"* whereas such lesions are common in patients with psoriasis. Erythema Cyratum Repens (ECR) Repens—Latin, participle from repo: to crawlorcreep. EGRwasfirstdescribedin 1952 by Gammel2 in a 56-year-old woman with carcinoma ofthe breast. He reviewed the literature on the cutat"ieous manifestations of internal malignancy and concluded that EGR was
Fig. 3. Erythema gyratum repens. Artist's rendering of original photograph from Gammel,^ page 497.
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dislinctive and also different from EAC and other annular erythemas. Clinical features and histology. There is a generalized eruption with parallel bands of erythema in an annularorgyratearrangement. It may resemble grains of wood and have a zebra-like appearance,^ although in the early stages the rash may resemble pityriasis rubra pilaris. Scaling is usually more tnarked in EGR than in EAC, which may be due to the more rapid movement ofthe former, which changes configuration daily, whereas EAC moves more slowly over a period of weeks.^^ Pevny^^ presented a list of differentiating features between EAC and EGR and in Gammel's original description of EGR,^ the keloid consistency of EAC was absent. Like EAC, there is relative sparing of the hands, feet and face and there are nonspecific changes on the scalp in EGR. Itching occurs although probably less marked than in EAC 2'^*''^" According to Pevny^" there are histoiogic differences between EGR and EAC, although other investigators were not convinced.^''^*^** Eigure 3 is adapted frotii Gammei's original description of EGR. Assoc/a(/on wilh malignancy. Although the condition is usually associated with malignancy (25 out of 26 reports) it has also been described wilh [Hilmonary tuberculosis.^^ Skolnick and Mainr"nan'"* reviewed 21 patients with EGR and malignancy although there have been others,^'"^^ including a 75year-old man with pulmonary carcinoma brought to ihe author's attention.""* Table 4 summarizes these 25 patients wilh EGR and malignancy. Ninety-two percent of patients had a carcinoma including lung, alimentary tract, urogenital tract and breast; the lung being involved in 44% of the cases, most of whon"i were men. The rash usually preceded the discovery of malignancy""-"-* and this phenomenon was first described by Gammel.^ Also, he first rec-
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Harrison Table 4. Erylhema Cyratum Repens and
Carcinoma of lung Carcinoma of uterus or cervix Carcinoma of breast Carcinoma ot stomach Carcinoma of anus Carcinoma of tongue Carcinoma of hypopharynx Carcinoma of bladder Carcinoma ot proslate Multiple myeloma Malignant melanoma Tola I
Average Age
1 1 patients (10 men, 1 sex unspecifiedl 3 patienls 2 patients (women) 2 patienls (1 man, I woman) 1 patient (woman) 1 patient (man) 1 patieni (man) 1 patieni (woman) 1 patient 1 patient (woman) 1 patient (man) 25 patienls (1 5 men, 9 women, 1 sex uns|jecified) 60 in those In which age specified
ogni/ed ihe improvement in the rash after treatment of the malignancy. Many patients experience some improvement, which varies Irom moderate to dramatic depending on the susceptibility of the malignancy to therapy. Discussion
Erylhema marginatum rheumaticum, associated with rheumatic fever, and erythema dyschronicum perstans are distinct and separate entities. ECM is recognized by its association with a tick or mosquito bite, usual occurrence in Euro|K', possibly associated meningitis and other constitutional symptoms, and the response to antibiotics. EAC may be distinguished from EGR as shown in Table 5. It Is doubtfiil whet her EAC is associated with malignancy and, although Bonniger and Happle^-'' and Pevny^^ described an association. White and Perry,"* after studying a large groupof patients with annu lar erythema, were unconvinced. However, the association of EGR with malignancy isestablished and the rash in most
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Table 5. Comparison Between Erylhema Annulare Centrifugum (EACi and Erythema Gyratum Repens (EGR) EAC
Association wilh malignancy Association with other diseases
EGR
Rarely Intections, drugs, breast hypertrophy, lupus erylhemalosus Annular conliguration of rash is variable
Clinical features
Scaling slight
Movement ot rash
May be induraled itching moderate Slowly over weeks
Yes, usually pulmonary carcinoma in men Tuberculosis
Characteristic appearance, like grains of wood Scaling, sometimes marked Not indurated Itching slighl Rapidly over days
Table adapted from various sources, including reference 56.
[lalietits has a characteristic appearance. The presence ol FGRshoukI |)rom|)t a search tor an underlying malignaticy, especially pulmonary in men. If no malignancy is found, the patient should be kept utider review atxl invesligalions repeated, since in some [)alients the rash has preceded the malignancy by n"iany months."" An indicalion for radiologic itivestigations in EGR contrasts with some other sklti tliseases, such as bullous |>em|.)higoid, where the case tor such investigations is unconvincing.''^' Lackot malignancy should not [irevetit a search for other causes of EGR si nee it has been described with [itilnionary tuberc"Lil()sis.^'^ ThetherapyofEACand EGR is limited (Table bland most improvement, especially in EGR, is obtained by treatmenl of the underlying cause, it this is known.
Table 6. 1. 2. 3. 4. 5.
Ireatnieni »i tAC and ECR
Treatment ot underlying condition. AntJhistamine-', Topical sleroids. Systemic steroids. AntJmetabolites.
Table adapted from various sources.
The clinical appearance and [jalhogenesis ol the annular erythemas are misunderstood and EAC and EGR may rei^resent similar reaction palterns to a stimLilus, one Lisually nonmalignant and the other malignanl. EAC and EGR can be louncl in the same patieni at different times,"" EAC develo|)ing betore tieo|ilasia was n"ianifest, although later FGR developed. Van Dijk"^ presetited a woman with uteritie carcinoma who had I'eatures of EAC and EGR [ireset"il simulUineously. Gammel^ discussed theories explaining the spreading nature of EGR and Becker etal.,'*^ in a discussion of EAC, felt that when associated with malignancy, there was a direct infiltration ofthe skin with malignant cells, although this would no longer be accepted. Lazar''" described EAC with tumor cells in the skin causing an immune reaction and interest in the immunology of the annu lar erythemas was stimulated by Shelley's description of a patient with EAC and massive breast hy[)ertrophy."*^ Circulating anti bodies to breast tissue with a positive LE phenon"ienon were present and the EAC disappeared alter surgical reduction of breast size. Itnmunologic mechanisms n"iay have been involved in a patient with EGR and pulmonary
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carcinoma."^ The various possibilities included: 1. Antibodies produced against tumor antigens cross-reacting wilh cutat"ieous antigens. 2. Tumor polypeptides acting as culaneous haptogens. 3. Circulating immune complexes. A similar patient with EGR and pulmonary carcinoma recently came to the author's attention."^ The immunofluorescence of involved skin resembled that reported by Holt and Davies,"''' with granular deposits of IgG and C.j in the basement membrane zone. The patient had elevated levels of carcinoembryonic antigen which may have participated In the pathogenesis of the rash. More immunologic studies ot the annuLir erythemas are required and are only hindered by the rarily of these conditions. Conclusions 1. The annular erythemas inclticle erythema chronicum migrans (ECM), erythema annulare cenlrifugum (EAC) and erythema gyratum repens (EGR). 2. ECM is associated with tick or mosquito bites, occurs mainly in Europe and responds well to antibiotics, especially penicillin. 3. EAC includes most of the other terms used for the annu lar erythemas. There are various etiologies but it israrely, ifat all associated with malignancy. It may bedislinguished from EGR clinically. 4. EGR is almost always associaled with malignancy, especially pulmonary malignancy in men. Acknowledgments iheaulhorthanksDr. I.S.Comaishforprovidinghelpful advice, and Mr. D, P, FHammersley lor preparing the illuslrations. References 1. Goltz, R. W.: The unusual figurate erylhemas. In: Dermatology in General Medicine, Edited by Fitzpal-
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rick, T. B., Arndt, K. A., Clerk, W. H., Eisen, A. Z., Van Scott, E. I., and Vaughan, |. H., New York, McGrawHill, 1971, 2. Gammel,). A.: Erythema gyratum repens. Skin manifestation in patient with carcln(jma of breast. A.M.A. Arch, Dermatol, Syphilol. 66:494, 1952. 3. Summerly, R,: Thetigurateerythemasarid neoplasia. Br. |. Dermalol. 76:370, 1964. 4. White,|.W.,,ind Perry, H.O.: Erythema perstans. Br. ), Dermalol. 81:641, 1969. 5. Tachau, P.: Erythema exudativum multilorme und nodosum. In: Handbi;ch der FHaut-und Geschlechtskrankheilen. Berlin, |ulius Springer, 1928. 6. Shelley, W, B.: Erylhema annulare centrifugum. A case due to hypersensitivity to blue cheese penicillium. Ar(h. Dermatol. 90:54, 1964. 7. Thivolet, I., Galiois, P., and Perrot, M.: Unedermatose paraneoplasique meconnue: I'erythema giralum repens. Rev. Lyon Med. 19:789, 1970. 8. Keil, Fl.: The rheumatic erythemas, A critical survey. Ann, Intern. Med. 11:2223, 1937. 9. Ramirez, C. O.: Quoted in Stevenson, M. |. R., and Miura, M.; Erythema dyschromicum [rerslans (ashy dermalosis). Arch. Dermaloi. 94:196, 1966. 10. Convit, I., KendeUVegas, F., and Rodriguez, G.: Erythema dyschromicum perstans. A hitherto underscribed skm disease. |. Invest. Dermalol. i6:457, 1961. 1 I. Stevenson, M. |. R,, and Miura, M.: Erythema dyschromicum perstans lashv dermalosisl. Arch, Dermatol. 94:196, 1966. 12. Knox, I, M., Dodge, B. G., and Freeman, K. G,: Erythema dyschromicum perstans. Arch, Dermatol. 97:262, 1968. I.t. Fit/patrt{k,T, B,,and Mihm,M,C., |r: Abnormalities ot the melanin pigmentary system. In: Dermatology in General Medicine. Edited by Fitzpatrick, T. B., et al.. New York, 1971. 14. Hoist. R., and Mobacken, H.: Erythema dyschromicum Persians (ash dermatosisi, Acta Derm. Venereol. 54:69, 1974. 15. Lever, W. F., and S( haumburg-Lever, G,: Histopalhology of the Skin, 5th ed. Philadelphia, 1. B. Lippjncoll Co., 1975. 16. Soler, N. A., Wand, C. H. T., and Freeman, R. G.: Ultraslru< tural |>a tho logy ot erythema dyschromicum |>erst,Tns. |. Invesl. Dcrmatol. 52:155, 1969, 17. Pinkus, H.: Lichenoid tissue reactions. Arcli. Dermaloi. 107:840. 1973. 18. Byrne, D. A., and Berger, R. S.: Ervthema dyschromicum perstans. A report of Iwo cases in fairskinned patients. Acta Derm. Venereol. 54:65,1974. 19. Atzeljus, A,: Erylhema chronicum mlgr.ins, Acta Derm. Venereol. 2:120, 1921. 20. Lipschul7, B.: Uber eine seltene erythemlorm (erythema chronicum migrans). Arch. Derm. Syph. 118:349, 1913. 21. Sonck, C. E.: Erythema chronicum migrans with multiple lesions, Acta Derm, Venereol. 45:34, 1964. 22. Scrimenti, R. |.: Erylhema chronicum migrans. Arch. Dermatol. 102:104, 1970.
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2.i. Smith, L. R., Burgdorf, W., and Katz, H. 1.; Erythema chronicum migrans. Cutis 17:962, 1976 24. Hellerslrdm, S.: Erythema chronicum migrans. Afzelii. Acta Derm. Venereol. 11:315, 19)0. 25. Hellerstrbm, S.i Erythema chronicum migrans. Alzelii with meningitis. Acta Derm. Venereol. 31:227,1951. 26. Weber, K.; Erylhema chronicum migrans meningitis—eine bakterielle infeklions krankheit? Munch. Med. Wochenschr. 116:1993, 1971. 27. Putkonen, T., Mutakallio, K. K., and Salminen, A.: Erylhema chronicum migrans with meningitis. A rare coincidence of two tick borne diseases? Dermatologica 125:184. 1962. 28. Degos, P. R., Touraine, R., and Aroutle,).: L'erythema chronicum migrans. (DiscLission d' une origine rickettsienne). Ann. Dermatol. Syphiligr. 89:247, 1962. 29. Harrison, P. V.: Personal observation, 1977. 30. Eox, T. C: Erythema gyratum perstans. Trans. Clin. Soc. Lond. 14:67, 1881. 31. Wende, G. W.: Erythema perstans with report of two cases involving circinale lesions. ). Cutan. Dis. 24:241, 1906. 32. Wende, G. W.: Erylhema figuratum perstans. |AMA 51:1936, 1908. 33. Darier, J.: De' I'erylheme annulaire centrifuge. Ann. DermatoL Syphiligr. 6:57, 1916. 34. Butler, J.: Erythema annulare cenlrifugum. A.M.A. Arch. Dermatol. Syphilol. 25:111, 1932. 35. Klaber, R.: Erythema gyratum perslans (Colcott Fox). A case report with discussion on relationship with erythema annulare centrifugum (Darier) and dermatitis herpeliformis. Br.). Dermatol. 58:111,1946. 36. Ereid, R., Schonberg, 1. L, and Litt, |. Z.: Erythema annulare centrifugum (Darier) in a newborn inlant.). Pediat. 50:66, 1957. 37. Gianotti, F., anci Ermicova, E.: Erythema gyratum alrophicans transiens neonate. Arch. Dermatol. 111:615, 1975. 38. Beare.). M., Froggart. P., lones, |. H., and Neill, D. W.: Familial annularerythema. An apparently new dominant mutation. Br. |. Dermalol. 78;.S9, 1966. 39. Kind. R.: Bullose varianle des erythema annulare centrifugum Darier bei candia-albicans-infeklion. Hautarzt. 26:466. 1975. 40. Ellis. F. A., and Friedman, A. A.: Erythema annulare centrifugum (Darier's). Clinical and histologic study. A.M.A. Arch. Dermatol. Syphilol. 70:496, 1954. 41. Hammaf. H.: Erythema annulare centrifugum coincident with Epstein-Barr virus iniection in an infant. Acta Paediat. Scand. 63:788. 1974. 42. Shelley, W. B.: Erythema annulare centrifugum due to Candida aibicans. Br. |. DermatoL 77:383, 1965. 43. lillson, O. P., and Koekelman, R. A.: Further amplification of the concept of dermatophytid. A.M.A. Arch. Dermatol. Syphilol. 66:738, 1952. 44. lillson, O. F.: Allergic confirmation that some cases of erythema annuiare centrifu^um are dermalophytids. A.M.A. Arch. Dermatol. Syphilol. 70:355, 1954. 45. Ashurst, P. |.: Erythema annulare centrifugum due to hydroxychloroquine sulphate and chloroquine sulphate. Arch. Dermatol. 95:37. 1969.
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46. Rekant, S. I., and Becker. L. E.: Autoimmune annular erythema. A variant of lupus ervthematosus. Arch. Dermatol. 107:424. 1973. 47. Shelley, W. B., and Hurley. FH. |.: An unusual autoimmune syndrome. Arch. Dermatol. 81:889, 1960. 48. Becker, S. W., Kahn, D., and Rothman, S.: Cutaneous manifestations of internal malignant tumors. A.M.A. Arch. Dermatol. Syphilol. 45:1069, 1942. 49. Stillians, A.: Erythema annulare centrifugum. Its relation to internal disease. A.M.A. Arch. Dermatol. Syphilol. 67:590, 1953. 50. Lazar, P.: Cancer, erythema annulare centrifugum and autoimmunity. Arch. Dermatol. 87:246. 1963. 51. Saikia, N. K.. Mackie, R. M., and McQueen A.: A case of bullous pemphigoid and figurate erythema in association with metastatic spread of carcinoma. Br. ). Dermatol. 88:331, 1973. 52. Everall. !. D.. Dowd, P. M., and Ardalan. B.: Unusual cutaneous associations of a malignant carcinoid tumor of the bronchus—erythema annulare centrifugum and white banding of the nails. Br. |. Dermatol. 93:341. 1975. 53. Bdnniger, F., and Happle. P.: Erythema annulare centrifugum als symptom einer akuten myeloischen leukaemic. Z. Hautkr. 52:77, 1977. 54. Baker, H., and Ryan. T. ).: Generalized pustular psoriasis. A clinical and epidemiological study of 104 cases. Br. |. Dermatol. 80:771, 1968. 55. Resnick, J. S.. and Cram, D. L.: Erythema annularelike pustular psoriasis. Arch. Dermatol. 108:687, 1973. 56. Pevny, V. I.: Erythema gyratum repens. Z. Hautkr. 8:260, 1966. 57. Thomson, 1., and Stankler, L.: Erythema gyralum pens. Reports of Iwo further cases associated with carcinoma. Br. |. Dermatol. 82:406, 1970. 58. Hochleitner, H., Bartsch. G . and Zelger, |.: Erythema gyratum repens bei bronchuscarcinom. Hautarzt. 21:116. 1970. 59. Barber. P. V., Doyle, L., Vickers, D. M.. and Hubbard, H.: Erythema gyratum repens with pulmonary tuberculosis. Br. |. Dermatol. 98:465, 1978. 60. Skolnick, M., and Mainman, E. R.: Erythema gyratum repens with metastic adenocarcinoma. Arch. Dermalol. 111:227, 197S. 61. Connor, B. L.: Erythema gyralum repens. Case presentation. Trans. St. lohn's Hosp. Dermatol. Soc. 58:323, 1972. 62. Lukowska, I., and Silny, W ; Erythema gyratum repens jako schor/enie paranowotoworowe. Przegl Dermatol. 61:785, 1974. 63. Holt, P. |. A., and Davies. M. G.: Erythema gyratun repens—an immunologically mediated dermatosis' Br. |. Dermatol. 96:343, 1977. 64. Dahl, M. G. L.: Personal communication, 1976. 65. Moss, A. A., and Hanelin. L. G.: Occult malignan tumors in cfermatologic disease. The futility o radiological search. Radiology 69:123, 1977. 66. Leavell. U. W., Winternitz. W. W.. and Black. |. H. Erythema gyralum repens and unditferentiated car cinoma. Arch. Dermatol. 95:69. 1967. 67. VanDijk. E.: Erythema gyratum repens. Der matologica 123:301, 1961.
