Periodic synopsis This report reflects the best data available at the time the report was prepared, hut caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations set forth in this report.
Lichenoid dermatoses and related disorders. II. Lichen nitidus, lichen sclerosus et atrophicus, benign lichenoid keratoses, lichen aureus, pityriasis lichenoides, and keratosis lichenoides chronica Paul A. Bleicher, MD, PhD,a, b Jeffrey S. Dover, MD, FRCPC,b,c and Kenneth A. Arndt, MDb,d Boston, Massachusetts
The lichenoid dermatoses are a heterogeneous group that share histologic or clinical features. Articles were selected from the literature of lichen planus and lichenoid drug-induced eruptions (reviewed in Part I, J AM ACAD DERMATOL 1990;22:288-92), lichen nitidus, lichen scIerosus et atrophicus, benign lichenoid keratosis, lichen aureus, pityriasis lichenoides, and keratosis lichenoides chronica. Only articles published since 1980 are included; they were chosen to highlight some of the major issues of each disease and to provide general articles. This article reviews various diseases that are loosely considered lichenoid, either clinically, pathologically, or historically. LICHEN NlTIDUS I. General references A. Arndt KA. Lichen nitidus, In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds., Dermatology in general medicine, 3rd ed. New York: McGrawHill,1987:967-73. A review of the limited literature on lichen nitidus. From the Laboratory of Molecular Immunology, Dana-Farber Cancer Institute,' the Department of Dermatology, Harvard Medical School.s the Division of Dermatology, New England Deaconess Hospital," and the Department of Dermatology, Beth Israel Hospital. Reprint requests: Kenneth A. Arndt, MD, Beth Israel Hospital, Department of Dermatology, 330 Brookline Ave" Boston, MA 02115.
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II. Specific references A. Clausen J, Jacobsen FK, Brandrup F. Lichen nitidus: electron microscopic and immunofluorescence studies. Acta Denn Venereal (Stockh)
1982;62:15-9. This ultrastructure study of a skin biopsy specimen from a patient with lichen nitidus demonstrated that the central portion of the lesion has disintegration of the basal layer with occasional colloid bodies. Acantholysis was noted on the border of the lesions. The dermal infiltrate was composed of macrophages, some with melanin and lymphocytes with convoluted nuclei that resembled Sezary cells. The ultrastructure of the lichen nitidus was reminiscent of that of lichen planus. The relation between these diseases is still not resolved. B. Ocampo J, Tome R. Generalized lichen nitidus. Report of two cases treated with asternizol. Int J Dermato11989;28:49-51. Two patients are described with generalized lichen nitidus. Both responded to astemizol with a rapid response in 6 to 12 days. C. Randle HW, Sander HM. Treatment of generalized lichen nitidus with PUVA. Int J Dermato11986;25:330-l. This article is a case report of a 29-year-old woman with extensive generalized lichen nitidus. With psoralens and ultraviolet A (PUVA) treatments three times per week, almost complete clearing was achieved at 27 treatments (20 joule/ crrr). This is the first report of this therapy for lichen nitidus,
671
Journal of the
672 Bleicher et al. LICHEN SCLEROSUS ET ATROPHICUS 1. General references A. Chalmers RJ, BurtonPA, BennettRF, etal. Lichen sclerosus et atrophicus. A common and distinctivecause of phimosis in boys. Arch DerrnatoI1984;120:1025-7. This study examined the histologicdata of 100 boys 5 to 11 years of age who were undergoing circumcisionfor disease of the foreskin, predominantly phimosis with or without balanitis. All lesions had the pathologic features of lichen sclerosuset atrophicus.The authors suggestthat scarring phimosis is one of the most common manifestations of lichen scelrosus et atrophicus. B. de Araujo VC, Orsini SC, Marucci G, et al. Lichen sclerosus et atrophicus. Oral Surg Oral Med Oral PathoI1985;60:655-7. A 26-year-old womanhad an intraoral plaque of lichen sclerosusthat involved the upper gingiva and labial mucosa. This is the second reported caseof isolated oral disease and onlythe twelfth case reported of oral involvement. Oral examinationsin patientswith lichen sclerosus should be performed. C. Friedrich EG. Vulvar dystrophy. Clin Obstet Gynecol1985;28:178-87. An in-depth review of current knowledge of lichen sclerosus et atrophicus from the point of view of the gynecologist. D. Handfield-Jones SE, Hinde FR, Kennedy CT. Lichen sclerosus et atrophicus in childrenmisdiagnosed as sexual abuse. Br Med J [Clin Res] 1987;294:1404-5. Twochildren withprepubertal lichensclerosuset atrophicus were initially thought to be the victimsof sexual abuse.This clearly written article should be essential reading for emergencyroom personnel and pediatricians. E. RidleyeM. Lichensclerosus et atrophicus.Arch DermatolI987;123:457-61. This excellent editorial reviews the recent literature on lichen sclerosus. The discussion of the relation of lichen sclerosus to the vulvar dystrophies summarizes an ongoing difficulty in communication among the specialties of medicine. F. Tremaine RDL, Miller RAW. Lichensclerosus et atrophicus, Int J DermatoI1989;28:1O-6. The authors have written an authoritative update on lichen sclerosus et atrophicus that emphasizes the recent literature on etiology, relationship to malignancy, associations, and therapy.
II. Familial and genetic A. Harrington CI, Gelsthorpe K. The association betweenlichensclerosus et atrophicus and HLAB40. Br J DermatoI1981;104:561-2.
American Academy of Dermatology
In a study of 50 patientswith lichen sclerosus the HLA haplotype B40 was found in 28% of patients and in 13.4% of 3000 control subjects. Although the finding was not significant after correctionwas made for the number of antigens checked,a suggestion oflinkage is made. Further study will be necessary to elucidate any HLA association. Other authors failed to find any significant HLA associations. III. Pathogenesis A. Friedrich EG, Kalra PS. Serum levels of sex hormones in vulvar lichen sclerosus and the effects of topical testosterone. N Engl J Med 1984;310:488-91. Serum levels of dihydrotestosterone(DHT) and androstenedione are decreased and free testosterone increased in untreated vulvar lichen sclerosus. After therapy with topical testosterone, both DHT and free testosterone are increased. The authors suggest that a depressed Sa-reductase levelcan induce lichen sclerosus et atrophicus. This would also explain the commonlyseenclearing ofchildhoodlichensclerosus at puberty when levels of DHT increase. B. Godeau G, Frances C, Hornebeck W, et al. Isolationand partial characterization ofan elastasetypeprotease in human vulvafibroblasts: its possibleinvolvement in vulvar elastic tissuedestruction of patients with lichen sclerosus et atrophicus. J Invest Dermatol 1982;78:270-5. Lichen sclerosus is associated with an almost complete disappearance of elastin-type superficial dermal material along with a homogenizationof collagen. The authors isolated an elastase from fibroblasts derived from the vulva. When the enzyme was injected into rabbits, degradation of elastic fibers was found locally. This article elucidates one likelystep in the pathogenesis of this puzzling disease. IV. Associated conditions A. ConnellyMG, Winkelman RK. Coexistence of lichen sclerosus, morphea, and lichen planus. Report of four casesand review of the literature. lAM ACAD DERMATOL 1985;12:844-51. Four cases of the association of these three diseasesare presented and eight cases from the literature are reviewed. Because scleroderma and lichenplanus changesare associatedwithchronic graft-versus-host disease, it is proposed that these diseases share a common pathogenesis in part. These patients also had immunologic abnormalities such as false-positive rapid plasma reagin,eosinophilia, leukopenia,rheumatoid factor, and vitiligo. B. Patterson lA, Ackerman AB. Lichen sclerosus et atrophicus is not related to morphea. A din-
Volume 22 Number 4 April 1990
Lichenoid dermatoses and related disorders . Part II 673
ical and histologic study of 24 patients in whom both conditions were reputed to be present simultaneously. Am J Dermatopathol 1984;6: 323-35. The relation between morphea and lichen sclerosus et atrophicus has been controversial for most of this century as documented in the 22 quotations by learned dermatologists in the introduction of this article. The authors examined 49 biopsy specimens from 24 patients in whom there was histologic evidence of morphea and lichen sclerosus et atrophicus coexisting. They concluded that all the supposed lichen sclerosus lesions were, in fact , morphea. The distinguishing features are the inflammatory infiltrate and sclerosis of the reticular dermis in these lesions, a finding consistent with morphea and not lichen scIerosus . They recommend a deep biopsy of dermis and subcutaneous tissue when this question is an important clinical issue. C. Harrington Cl, Dunsmore lR. An investigation into the incidence of autoimmune disorders in patients with lichen sclerosus et atrophicus. Br J Dermatol 1981;104:563-6. Several articles, including this early one, have been published on the association of lichen sclerosus et atrophicus autoimmune antibodies and autoimmune diseases . Other authors have questioned the statistical significance of such studies. No firm conclusion can currently be drawn about these associations.
V. Therapy A. Neuhofer J, Fritsch P. Treatment of localized scleroderma and lichen sclerosus with etretinate. Acta Derm Venerol (Stockh) 1984;64:170-4 . Romppanen U . Long-term results of etretinate therapy in vulvar dystrophy. CUIT Ther Res 1986;40:442-7. Romppanen U, Rantala I , Lauslahti K, et al. Light- and electron-microscopic findings in lichen sclerosus of the vulva during etretinate treatment. Dermatologica 1987;175:33-40. Etretinate therapy was attempted because of the known depression of collagen synthesis in fibroblasts cultured with retinoic acid. Romppanen et al. have demonstrated reduced pruritus, hyperkeratosis, and dystrophy in an open trial of 29 patients. The benefit was maintained in 11 of 29 patients for 2 years after the 3-month course of therapy. Immunoelectron microscopy, electron microscopy, and light microscopy showed normalization of the inflammatory, atrophic, and hyperkeratotic features. However, the number of
elastic fibers did not return to normal despite the clinical remission. B. Penneys NS. Treatment of lichen sclerosus with potassium para-aminobenzoate. J AM ACAD DERMATOL 1984;10 :1039-42. Potassium paraaminobenzoate (POTABA) may inhibit mucopolysaccharide secretion by fibroblasts. This author found improvement in five patients with lichen sclerosus treated with POTABA. The drug has relatively few side effects, and a trial may be worthwhile in those patients who fail to respond to other modalities.
Key points 1. Scarring phimosis isa common manifestation of lichen sclerosus in boys. 2. Lichen sclerosus et atrophicus in young girls may be misdiagnosed as sexual abuse, especially when erythema or hemorrhage erosions are present. 3. Genetic, environmental, and local factors seem to be important in the pathogenesis of lichen sclerosus et atrophicus. 4. Low Sa-reductase levels may be important in the pathogenesis of lichen sclerosus et atro-
phicus, 5. Controversy exists as to the coexistence of lichen sclerosus atrophicus and morphea in the same person. 6. Uncontrolled trials suggest that etretinate is effective in some cases of lichen sclerosus et atrophicus.
BENIGN LICHENOID KERATOSES 1. Specific references A. Barranco VP. Multiple benign lichenoid keratoses simulating photodermatoses: evolution from senile lentigines and their spontaneous regression. J AM ACAD DERMATOL 1985;13: 201-6. Fourteen patients with multiple benign lichenoid keratoses were studied. These patients, mostly women, had the sudden eruption of the lichenoid lesions in preexisting senile lentigines in predominantly photodistributed locations. Initially these eruptions were m istaken for lupus erythematosus and drug-induced photodermatitis. B. Frigy AF, Cooper PH. Benign lichenoid keratosis. Am J Clin Pathol 1985;83:439-43. This is a well-done clinicopathologic correlation of 29 patients ranging in age from 28 to 81 years with benign lichenoid keratoses. The patients were predominantly women and the lesions were located primarily on the chest, arms, and face. The principal histologic feature was a lichenoid infiltrate, a hyperplastic epidermis, and an association of 17 lesions with senile lentigines. The
674
Bleicher et al. authors suggest that the diseaseis a response to a preexisting lentigo or an actinic or seborrheic keratosis. C. Laur WE, Posey RE,WallerJD. Lichen planuslike keratosis: a clinicohistopathologic correlation. J AM ACAD DERMATOL 1981;4:329-36. The clinical and pathologic features of the benignlichenoid keratosis are summarized in this review. The clinical colorillustrations are excellent.The authorsstress the importance of distinguishing this lesion from intraepithelial carcinoma (including Bowen's disease). These solitary lesions are most common in women older than 58 years, are found primarily on the upper extremities, and are often associated with senile lentigines. The lesion can be suspected clinically but a biopsy is mandatory to eliminate the possibility of malignancy.
Key points 1. Benign lichenoid keratoses are found predominantly on sun-exposed skin in women.
2.These keratoses may represent lichenoid reactions to preexisting benign cutaneous lesions, such as solar lentigines, because they are often associated histologically with these lesions. LICHEN AUREUS I. General and specific references A. Price ML, Jones EW, Calnan CD, et al. Lichen aureus:a localized persistent form of pigmented purpuric dermatitis. Br J Dermatol 1985; 112:307-14. A review of 42 patients withlichenaureus by the originatorofthe term (C. C.). The yellow-brown color is characteristic. The legs are the most common area of involvement, but any area can be involved.Thelichenoid tissuereaction is more densethan inotherpigmented purpuras. A study of factor VII antigen and Ulex europaeus lectin markersof endothelial cells showedslight loss of factorVII andlittlechangeofthe lectin pattern. This finding indicates that no gross endothelial changes couldbe found to explain the lesions. PITYRIASIS LICHENOIDES I. General references A. Nigra TP, Soter NA. Pityriasis lichenoides, In: FitzpatrickTB, Eisen AZ, Wolff K, et al., eds., Dermatology in generalmedicine, 3rd ed. New York: McGraw-Hill, 1987:1006-9. A succinctreview of all but the most recent literature on both acute and chronic pityriasis lichenoides. The recentdata on immunohistopa-
Journal of t he American Academy of Dermatology
thology have added much to the knowledge of this disease. B. Willemze R, Scheffer E . Clinical and histologic differentiation betweenlymphomatoid papulosis and pityriasis lichenoides. J AM ACAD DERMA· TOl1985;13:418-28. Eighty-two patients with pityriasis lichenoides are compared with 26 patients with lymphomatoid papulosis to find histologicand clinical features to distinguishthese diseases. The discussion emphasizes the clinical distinction of these entities and includes a summary table of the distinguishing histologicfeatures. II. Specificreferences A. Hood AF, Mark EJ. Histopathologic diagnosis of pityriasis lichenoides et varioliformis acuta and its clinical correlation. Arch Dermatol 1982;118:478-82. Longley J, Demar L, Feinstein RP, et al. Clinical and histologic features of pityriasis lichenoides et varioliformis acuta in children. Arch DermatoI1987;123 :1335-9. Both these studies examine the accuracy of the diagnosisof pityriasislichenoideset varioliformis acuta (PLEVA) by histologic and clinical features. Hood and Mark studied the clinicaldiagnoses of 42 patients who had biopsy specimens thought to be histologically consistent with PLEVA. Sixteen had a clinical diagnosis of PLEVA. More than 50% of the rest were diagnosedashaving either pityriasisrosea, insectbite, or eczematoid eruption. Intraepiderma1erythrocytes, once thought to be pathognomonic for PLEVA, werefound in 39 of 42specimens.In the study ofLongleyet al.,fivechildren youngerthan 11 yearsofage withthediagnosisofPLEVA were examined for histologic and clinical features. In contrast to Hood and Mark, these authors found that other eruptions in children may be clinically confused with PLEVA, specifically insect bites, eczema, varicella, erythema multiforme, and Gianotti-Crosti syndrome. Rather than clinical overdiagnosis as suggested by Hood et al. for adults, these authors suspect underdiagnosis in children. They suggest a high index of suspicion be kept for PLEVA in children. B. LeVine MJ. Phototherapy of pityriasis lichenoides. Arch Dermatol 1983;119:378-80. Powell FC, Muller SA. Psoralens and ultraviolet A therapy of pityriasis lichenoides. J AM ACAD DERMATOL 1984;10:59-64.
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Lichenoid dermatoses and related disorders. Part II 675
Truhan AP, Hebert AA, Esterly NB. Pityriasis lichenoides in children: therapeutic response in erythromycin. J AM ACAD DERMATaL 1986; 15:66-70. In 11 patients erythemogenic dosages of UVB cleared pityriasis lichenoides in an average of 29 treatments. However, all patients required maintainence therapy. Similarly, Powell and Muller treated three patients with PUVA, which cleared the skin. Truhan et al. showed that 11 of 15children with pityriasis lichenoides ( 11 with PLEVA, 4 with pityriasis lichenoides chronica) had disease remission with erythromycin therapy for 2 to 5 months. Seven of these children discontinued erythromycin without recurrence of lesions. C. Muhlbauer JE, Bhan AK, Harrist TJ, et al, Immunopathology of pityriasis lichenoides acuta. JAM ACAD DERMATOL 1984;10:783-95. Weiss LM, Wood GS, Ellisen LW, et al. Clonal T-cell populations in pityriasis lichenoides et varioliformis acuta (Much a-Haberman disease). Am J Pathol 1987;126:417-21. Wood GS, Strickler JG, Abel EA, et al. Immunohistology of pityriasis lichenoides et varialiformis acuta and pityriasis lichenoides chronica. Evidence for their interrelationship with lymphomatoid papulosis. J AM ACAD DERMATOL 1987;16:559-70. Muhlbauer et al. demonstrated cell-mediated cytotoxicity is probably a major mechanism in the pathogenesis of PLEVA. A detailed immunohistologic study of six patients with pityriasis lichenoides by Wood et al. shows that the histologic changes of PLEVA are similar to those of lymphomatoid papulosis except that in the latter, large atypical cells are also present. The similarity of PLEVA and lymphomatoid papulosis is underscored by Weiss et al. who examined three cases of PLEVA for evidence of monoclonal T cell receptor rearrangment. In each case, a unique rearrangement of the T cell receptor is found in at least a small percentage of the cells. This result strongly supports the hypothesis that,
in some instances, PLEVA may belong in the category of lymphoproliferative rather than inflammatory dermatoses. However, T cell clonality is not equivalent to malignancy. Key points
1. PLEVA in children is similar clinically to disease found in adults except that scalp and mucous membrane lesions are not seen. 2. The histologic features of PLEVA may be confused with other diseases, especially pityriasis rosea, insect bites, and eczematoid eruptions. Intraepidennal red cells are not pathognomonic of PLEVA. 3. UVB and PUVA phototherapy are effective palliative treatments for pityriasis lichenoides chronica although it is unknown whether they alter the natural history of the disease. 4. Children with either PLEVA or pityriasis lichenoideschronica may respond to oral erythromycin therapy. 5. Clonal T cell populations with a unique rearrangement of the T cell receptor have been found in some patients with PLEVA and lymphomatoid papulosis. Although this does not prove that PLEVA is a malignant process, it suggests that some cases may be proliferative rather than inflammatory, KERATOSIS LICHENOIDES CHRONICA (NEEKHAM'S DISEASE) 1. Specific reference A. Kersey P, Ive FA. Keratosis lichenoides chronica is synonymous with lichen planus. Clin Exp Dermatol 1982;7:49-54. A case report of keratosis lichenoides chronica with a review of the literature. The authors emphasize that there has been little uniformity of diagnostic features in previous reports of this rare disease. Linear and reticulate hyperkeratotic features are the only common features in most reports. Intraoral erosion, palm and sole involvement, and nail dystrophy were described in many reports. In all biopsy specimens dense lymphocyte infiltrates at the dermoepidermal junction were seen and colloid bodies and IgM deposits have been reported. The authors conclude that keratosis lichenoides chronica is a form of hypertrophic lichen planus.
Lichenoid dermatoses and related disorders. II. Lichen nitidus, lichen sclerosus et atrophicus, benign lichenoid keratoses, lichen aureus, pityriasis lichenoides, and keratosis lichenoides chronica Paul A. Bleicher, MD, PhD,a, b Jeffrey S. Dover, MD, FRCPC,b,c and Kenneth A. Arndt, MDb,d Boston, Massachusetts
The lichenoid dermatoses are a heterogeneous group that share histologic or clinical features. Articles were selected from the literature of lichen planus and lichenoid drug-induced eruptions (reviewed in Part I, J AM ACAD DERMATOL 1990;22:288-92), lichen nitidus, lichen scIerosus et atrophicus, benign lichenoid keratosis, lichen aureus, pityriasis lichenoides, and keratosis lichenoides chronica. Only articles published since 1980 are included; they were chosen to highlight some of the major issues of each disease and to provide general articles. This article reviews various diseases that are loosely considered lichenoid, either clinically, pathologically, or historically. LICHEN NlTIDUS I. General references A. Arndt KA. Lichen nitidus, In: Fitzpatrick TB, Eisen AZ, Wolff K, et al., eds., Dermatology in general medicine, 3rd ed. New York: McGrawHill,1987:967-73. A review of the limited literature on lichen nitidus. From the Laboratory of Molecular Immunology, Dana-Farber Cancer Institute,' the Department of Dermatology, Harvard Medical School.s the Division of Dermatology, New England Deaconess Hospital," and the Department of Dermatology, Beth Israel Hospital. Reprint requests: Kenneth A. Arndt, MD, Beth Israel Hospital, Department of Dermatology, 330 Brookline Ave" Boston, MA 02115.
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II. Specific references A. Clausen J, Jacobsen FK, Brandrup F. Lichen nitidus: electron microscopic and immunofluorescence studies. Acta Denn Venereal (Stockh)
1982;62:15-9. This ultrastructure study of a skin biopsy specimen from a patient with lichen nitidus demonstrated that the central portion of the lesion has disintegration of the basal layer with occasional colloid bodies. Acantholysis was noted on the border of the lesions. The dermal infiltrate was composed of macrophages, some with melanin and lymphocytes with convoluted nuclei that resembled Sezary cells. The ultrastructure of the lichen nitidus was reminiscent of that of lichen planus. The relation between these diseases is still not resolved. B. Ocampo J, Tome R. Generalized lichen nitidus. Report of two cases treated with asternizol. Int J Dermato11989;28:49-51. Two patients are described with generalized lichen nitidus. Both responded to astemizol with a rapid response in 6 to 12 days. C. Randle HW, Sander HM. Treatment of generalized lichen nitidus with PUVA. Int J Dermato11986;25:330-l. This article is a case report of a 29-year-old woman with extensive generalized lichen nitidus. With psoralens and ultraviolet A (PUVA) treatments three times per week, almost complete clearing was achieved at 27 treatments (20 joule/ crrr). This is the first report of this therapy for lichen nitidus,
671
Journal of the
672 Bleicher et al. LICHEN SCLEROSUS ET ATROPHICUS 1. General references A. Chalmers RJ, BurtonPA, BennettRF, etal. Lichen sclerosus et atrophicus. A common and distinctivecause of phimosis in boys. Arch DerrnatoI1984;120:1025-7. This study examined the histologicdata of 100 boys 5 to 11 years of age who were undergoing circumcisionfor disease of the foreskin, predominantly phimosis with or without balanitis. All lesions had the pathologic features of lichen sclerosuset atrophicus.The authors suggestthat scarring phimosis is one of the most common manifestations of lichen scelrosus et atrophicus. B. de Araujo VC, Orsini SC, Marucci G, et al. Lichen sclerosus et atrophicus. Oral Surg Oral Med Oral PathoI1985;60:655-7. A 26-year-old womanhad an intraoral plaque of lichen sclerosusthat involved the upper gingiva and labial mucosa. This is the second reported caseof isolated oral disease and onlythe twelfth case reported of oral involvement. Oral examinationsin patientswith lichen sclerosus should be performed. C. Friedrich EG. Vulvar dystrophy. Clin Obstet Gynecol1985;28:178-87. An in-depth review of current knowledge of lichen sclerosus et atrophicus from the point of view of the gynecologist. D. Handfield-Jones SE, Hinde FR, Kennedy CT. Lichen sclerosus et atrophicus in childrenmisdiagnosed as sexual abuse. Br Med J [Clin Res] 1987;294:1404-5. Twochildren withprepubertal lichensclerosuset atrophicus were initially thought to be the victimsof sexual abuse.This clearly written article should be essential reading for emergencyroom personnel and pediatricians. E. RidleyeM. Lichensclerosus et atrophicus.Arch DermatolI987;123:457-61. This excellent editorial reviews the recent literature on lichen sclerosus. The discussion of the relation of lichen sclerosus to the vulvar dystrophies summarizes an ongoing difficulty in communication among the specialties of medicine. F. Tremaine RDL, Miller RAW. Lichensclerosus et atrophicus, Int J DermatoI1989;28:1O-6. The authors have written an authoritative update on lichen sclerosus et atrophicus that emphasizes the recent literature on etiology, relationship to malignancy, associations, and therapy.
II. Familial and genetic A. Harrington CI, Gelsthorpe K. The association betweenlichensclerosus et atrophicus and HLAB40. Br J DermatoI1981;104:561-2.
American Academy of Dermatology
In a study of 50 patientswith lichen sclerosus the HLA haplotype B40 was found in 28% of patients and in 13.4% of 3000 control subjects. Although the finding was not significant after correctionwas made for the number of antigens checked,a suggestion oflinkage is made. Further study will be necessary to elucidate any HLA association. Other authors failed to find any significant HLA associations. III. Pathogenesis A. Friedrich EG, Kalra PS. Serum levels of sex hormones in vulvar lichen sclerosus and the effects of topical testosterone. N Engl J Med 1984;310:488-91. Serum levels of dihydrotestosterone(DHT) and androstenedione are decreased and free testosterone increased in untreated vulvar lichen sclerosus. After therapy with topical testosterone, both DHT and free testosterone are increased. The authors suggest that a depressed Sa-reductase levelcan induce lichen sclerosus et atrophicus. This would also explain the commonlyseenclearing ofchildhoodlichensclerosus at puberty when levels of DHT increase. B. Godeau G, Frances C, Hornebeck W, et al. Isolationand partial characterization ofan elastasetypeprotease in human vulvafibroblasts: its possibleinvolvement in vulvar elastic tissuedestruction of patients with lichen sclerosus et atrophicus. J Invest Dermatol 1982;78:270-5. Lichen sclerosus is associated with an almost complete disappearance of elastin-type superficial dermal material along with a homogenizationof collagen. The authors isolated an elastase from fibroblasts derived from the vulva. When the enzyme was injected into rabbits, degradation of elastic fibers was found locally. This article elucidates one likelystep in the pathogenesis of this puzzling disease. IV. Associated conditions A. ConnellyMG, Winkelman RK. Coexistence of lichen sclerosus, morphea, and lichen planus. Report of four casesand review of the literature. lAM ACAD DERMATOL 1985;12:844-51. Four cases of the association of these three diseasesare presented and eight cases from the literature are reviewed. Because scleroderma and lichenplanus changesare associatedwithchronic graft-versus-host disease, it is proposed that these diseases share a common pathogenesis in part. These patients also had immunologic abnormalities such as false-positive rapid plasma reagin,eosinophilia, leukopenia,rheumatoid factor, and vitiligo. B. Patterson lA, Ackerman AB. Lichen sclerosus et atrophicus is not related to morphea. A din-
Volume 22 Number 4 April 1990
Lichenoid dermatoses and related disorders . Part II 673
ical and histologic study of 24 patients in whom both conditions were reputed to be present simultaneously. Am J Dermatopathol 1984;6: 323-35. The relation between morphea and lichen sclerosus et atrophicus has been controversial for most of this century as documented in the 22 quotations by learned dermatologists in the introduction of this article. The authors examined 49 biopsy specimens from 24 patients in whom there was histologic evidence of morphea and lichen sclerosus et atrophicus coexisting. They concluded that all the supposed lichen sclerosus lesions were, in fact , morphea. The distinguishing features are the inflammatory infiltrate and sclerosis of the reticular dermis in these lesions, a finding consistent with morphea and not lichen scIerosus . They recommend a deep biopsy of dermis and subcutaneous tissue when this question is an important clinical issue. C. Harrington Cl, Dunsmore lR. An investigation into the incidence of autoimmune disorders in patients with lichen sclerosus et atrophicus. Br J Dermatol 1981;104:563-6. Several articles, including this early one, have been published on the association of lichen sclerosus et atrophicus autoimmune antibodies and autoimmune diseases . Other authors have questioned the statistical significance of such studies. No firm conclusion can currently be drawn about these associations.
V. Therapy A. Neuhofer J, Fritsch P. Treatment of localized scleroderma and lichen sclerosus with etretinate. Acta Derm Venerol (Stockh) 1984;64:170-4 . Romppanen U . Long-term results of etretinate therapy in vulvar dystrophy. CUIT Ther Res 1986;40:442-7. Romppanen U, Rantala I , Lauslahti K, et al. Light- and electron-microscopic findings in lichen sclerosus of the vulva during etretinate treatment. Dermatologica 1987;175:33-40. Etretinate therapy was attempted because of the known depression of collagen synthesis in fibroblasts cultured with retinoic acid. Romppanen et al. have demonstrated reduced pruritus, hyperkeratosis, and dystrophy in an open trial of 29 patients. The benefit was maintained in 11 of 29 patients for 2 years after the 3-month course of therapy. Immunoelectron microscopy, electron microscopy, and light microscopy showed normalization of the inflammatory, atrophic, and hyperkeratotic features. However, the number of
elastic fibers did not return to normal despite the clinical remission. B. Penneys NS. Treatment of lichen sclerosus with potassium para-aminobenzoate. J AM ACAD DERMATOL 1984;10 :1039-42. Potassium paraaminobenzoate (POTABA) may inhibit mucopolysaccharide secretion by fibroblasts. This author found improvement in five patients with lichen sclerosus treated with POTABA. The drug has relatively few side effects, and a trial may be worthwhile in those patients who fail to respond to other modalities.
Key points 1. Scarring phimosis isa common manifestation of lichen sclerosus in boys. 2. Lichen sclerosus et atrophicus in young girls may be misdiagnosed as sexual abuse, especially when erythema or hemorrhage erosions are present. 3. Genetic, environmental, and local factors seem to be important in the pathogenesis of lichen sclerosus et atrophicus. 4. Low Sa-reductase levels may be important in the pathogenesis of lichen sclerosus et atro-
phicus, 5. Controversy exists as to the coexistence of lichen sclerosus atrophicus and morphea in the same person. 6. Uncontrolled trials suggest that etretinate is effective in some cases of lichen sclerosus et atrophicus.
BENIGN LICHENOID KERATOSES 1. Specific references A. Barranco VP. Multiple benign lichenoid keratoses simulating photodermatoses: evolution from senile lentigines and their spontaneous regression. J AM ACAD DERMATOL 1985;13: 201-6. Fourteen patients with multiple benign lichenoid keratoses were studied. These patients, mostly women, had the sudden eruption of the lichenoid lesions in preexisting senile lentigines in predominantly photodistributed locations. Initially these eruptions were m istaken for lupus erythematosus and drug-induced photodermatitis. B. Frigy AF, Cooper PH. Benign lichenoid keratosis. Am J Clin Pathol 1985;83:439-43. This is a well-done clinicopathologic correlation of 29 patients ranging in age from 28 to 81 years with benign lichenoid keratoses. The patients were predominantly women and the lesions were located primarily on the chest, arms, and face. The principal histologic feature was a lichenoid infiltrate, a hyperplastic epidermis, and an association of 17 lesions with senile lentigines. The
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Bleicher et al. authors suggest that the diseaseis a response to a preexisting lentigo or an actinic or seborrheic keratosis. C. Laur WE, Posey RE,WallerJD. Lichen planuslike keratosis: a clinicohistopathologic correlation. J AM ACAD DERMATOL 1981;4:329-36. The clinical and pathologic features of the benignlichenoid keratosis are summarized in this review. The clinical colorillustrations are excellent.The authorsstress the importance of distinguishing this lesion from intraepithelial carcinoma (including Bowen's disease). These solitary lesions are most common in women older than 58 years, are found primarily on the upper extremities, and are often associated with senile lentigines. The lesion can be suspected clinically but a biopsy is mandatory to eliminate the possibility of malignancy.
Key points 1. Benign lichenoid keratoses are found predominantly on sun-exposed skin in women.
2.These keratoses may represent lichenoid reactions to preexisting benign cutaneous lesions, such as solar lentigines, because they are often associated histologically with these lesions. LICHEN AUREUS I. General and specific references A. Price ML, Jones EW, Calnan CD, et al. Lichen aureus:a localized persistent form of pigmented purpuric dermatitis. Br J Dermatol 1985; 112:307-14. A review of 42 patients withlichenaureus by the originatorofthe term (C. C.). The yellow-brown color is characteristic. The legs are the most common area of involvement, but any area can be involved.Thelichenoid tissuereaction is more densethan inotherpigmented purpuras. A study of factor VII antigen and Ulex europaeus lectin markersof endothelial cells showedslight loss of factorVII andlittlechangeofthe lectin pattern. This finding indicates that no gross endothelial changes couldbe found to explain the lesions. PITYRIASIS LICHENOIDES I. General references A. Nigra TP, Soter NA. Pityriasis lichenoides, In: FitzpatrickTB, Eisen AZ, Wolff K, et al., eds., Dermatology in generalmedicine, 3rd ed. New York: McGraw-Hill, 1987:1006-9. A succinctreview of all but the most recent literature on both acute and chronic pityriasis lichenoides. The recentdata on immunohistopa-
Journal of t he American Academy of Dermatology
thology have added much to the knowledge of this disease. B. Willemze R, Scheffer E . Clinical and histologic differentiation betweenlymphomatoid papulosis and pityriasis lichenoides. J AM ACAD DERMA· TOl1985;13:418-28. Eighty-two patients with pityriasis lichenoides are compared with 26 patients with lymphomatoid papulosis to find histologicand clinical features to distinguishthese diseases. The discussion emphasizes the clinical distinction of these entities and includes a summary table of the distinguishing histologicfeatures. II. Specificreferences A. Hood AF, Mark EJ. Histopathologic diagnosis of pityriasis lichenoides et varioliformis acuta and its clinical correlation. Arch Dermatol 1982;118:478-82. Longley J, Demar L, Feinstein RP, et al. Clinical and histologic features of pityriasis lichenoides et varioliformis acuta in children. Arch DermatoI1987;123 :1335-9. Both these studies examine the accuracy of the diagnosisof pityriasislichenoideset varioliformis acuta (PLEVA) by histologic and clinical features. Hood and Mark studied the clinicaldiagnoses of 42 patients who had biopsy specimens thought to be histologically consistent with PLEVA. Sixteen had a clinical diagnosis of PLEVA. More than 50% of the rest were diagnosedashaving either pityriasisrosea, insectbite, or eczematoid eruption. Intraepiderma1erythrocytes, once thought to be pathognomonic for PLEVA, werefound in 39 of 42specimens.In the study ofLongleyet al.,fivechildren youngerthan 11 yearsofage withthediagnosisofPLEVA were examined for histologic and clinical features. In contrast to Hood and Mark, these authors found that other eruptions in children may be clinically confused with PLEVA, specifically insect bites, eczema, varicella, erythema multiforme, and Gianotti-Crosti syndrome. Rather than clinical overdiagnosis as suggested by Hood et al. for adults, these authors suspect underdiagnosis in children. They suggest a high index of suspicion be kept for PLEVA in children. B. LeVine MJ. Phototherapy of pityriasis lichenoides. Arch Dermatol 1983;119:378-80. Powell FC, Muller SA. Psoralens and ultraviolet A therapy of pityriasis lichenoides. J AM ACAD DERMATOL 1984;10:59-64.
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Truhan AP, Hebert AA, Esterly NB. Pityriasis lichenoides in children: therapeutic response in erythromycin. J AM ACAD DERMATaL 1986; 15:66-70. In 11 patients erythemogenic dosages of UVB cleared pityriasis lichenoides in an average of 29 treatments. However, all patients required maintainence therapy. Similarly, Powell and Muller treated three patients with PUVA, which cleared the skin. Truhan et al. showed that 11 of 15children with pityriasis lichenoides ( 11 with PLEVA, 4 with pityriasis lichenoides chronica) had disease remission with erythromycin therapy for 2 to 5 months. Seven of these children discontinued erythromycin without recurrence of lesions. C. Muhlbauer JE, Bhan AK, Harrist TJ, et al, Immunopathology of pityriasis lichenoides acuta. JAM ACAD DERMATOL 1984;10:783-95. Weiss LM, Wood GS, Ellisen LW, et al. Clonal T-cell populations in pityriasis lichenoides et varioliformis acuta (Much a-Haberman disease). Am J Pathol 1987;126:417-21. Wood GS, Strickler JG, Abel EA, et al. Immunohistology of pityriasis lichenoides et varialiformis acuta and pityriasis lichenoides chronica. Evidence for their interrelationship with lymphomatoid papulosis. J AM ACAD DERMATOL 1987;16:559-70. Muhlbauer et al. demonstrated cell-mediated cytotoxicity is probably a major mechanism in the pathogenesis of PLEVA. A detailed immunohistologic study of six patients with pityriasis lichenoides by Wood et al. shows that the histologic changes of PLEVA are similar to those of lymphomatoid papulosis except that in the latter, large atypical cells are also present. The similarity of PLEVA and lymphomatoid papulosis is underscored by Weiss et al. who examined three cases of PLEVA for evidence of monoclonal T cell receptor rearrangment. In each case, a unique rearrangement of the T cell receptor is found in at least a small percentage of the cells. This result strongly supports the hypothesis that,
in some instances, PLEVA may belong in the category of lymphoproliferative rather than inflammatory dermatoses. However, T cell clonality is not equivalent to malignancy. Key points
1. PLEVA in children is similar clinically to disease found in adults except that scalp and mucous membrane lesions are not seen. 2. The histologic features of PLEVA may be confused with other diseases, especially pityriasis rosea, insect bites, and eczematoid eruptions. Intraepidennal red cells are not pathognomonic of PLEVA. 3. UVB and PUVA phototherapy are effective palliative treatments for pityriasis lichenoides chronica although it is unknown whether they alter the natural history of the disease. 4. Children with either PLEVA or pityriasis lichenoideschronica may respond to oral erythromycin therapy. 5. Clonal T cell populations with a unique rearrangement of the T cell receptor have been found in some patients with PLEVA and lymphomatoid papulosis. Although this does not prove that PLEVA is a malignant process, it suggests that some cases may be proliferative rather than inflammatory, KERATOSIS LICHENOIDES CHRONICA (NEEKHAM'S DISEASE) 1. Specific reference A. Kersey P, Ive FA. Keratosis lichenoides chronica is synonymous with lichen planus. Clin Exp Dermatol 1982;7:49-54. A case report of keratosis lichenoides chronica with a review of the literature. The authors emphasize that there has been little uniformity of diagnostic features in previous reports of this rare disease. Linear and reticulate hyperkeratotic features are the only common features in most reports. Intraoral erosion, palm and sole involvement, and nail dystrophy were described in many reports. In all biopsy specimens dense lymphocyte infiltrates at the dermoepidermal junction were seen and colloid bodies and IgM deposits have been reported. The authors conclude that keratosis lichenoides chronica is a form of hypertrophic lichen planus.
