Commentary

A t the end of World War II, lupus erythemato- sus (LE) was still considered a rare, often fatal disease that afflicted predominantly young women; nothing was known of its mecha-

nisms. Today, less than 50 years later, the volume of information, particularly about immunologic abnormali- ties and diverse clinical manifestations of LE and other connective tissue diseases, is so great that this issue of Clinics in Dermatology on collagen diseases from labora- tory to clinic faces an impossible challenge. The axiom, “to know everything about collagen diseases is to know everything about medicine” can now be extended to, “- medicine and immunology.” The introduction to this issue presented by the Medical Director of the Lupus Foundation of America, and one of the leading experts on lupus in this country, Robert Lahita, stresses the bewil- dering complexity of clinical and laboratory findings in collagen diseases, such as discoid LE, subacute cutaneous LE, and other variants of systemic LE.l

similar contrasts in the spectrum of clinical findings. On the one hand, the bullous lesions of most cases of pem- phigus vulgaris are rather characteristic; experienced der- matologists can recognize a large proportion of cases clin- ically; but even the best of clinicians are faced with such an apparently endless continuum of clinical manifesta- tions of collagen diseases that laboratory studies play an increasingly important role in the classification of these conditions.

Laboratory Findings

New Knowledge The explosive growth of our knowledge of the role of immunologic abnormalities in collagen diseases started with the then startling discovery of Miescher and Fau- connet* in 1954 that the LE cell phenomenon is mediated by nuclear autoantibodies. Thus, the scholarly historical perspectives of collagen diseases presented by Peter Miescher and his associate, Alessandra Tucci, give rare insight into the beginning of our present understanding of the immunology of collagen diseases.3

At one end of this spectrum is cutaneous LE; the only characteristic immunologic abnormality is the so-called lupus band test in skin lesions as demonstrated by direct immunofluorescence. The exhaustive studies of Blaszc- zyk and her associates of over 2500 cases document this exceptionally we11.5 Like the findings in all other connec- tive tissue diseases, these lupus band test reactions in the junctional region of the skin are not entirely specific. Moving into the spectrum of systemic LE, the same test system reveals not only such bands of immune deposits at the dermal- epidermal junction but also other immuno- logic abnormalities. The scholarly review of this subject by Velthuis and colleagues6 focuses on the most relevant immune deposits, some of which reflect the presence of characteristic circulating autoantibodies. To cope with the evaluation of the relative sensitivity and specificity of these complexes of immune deposits, Velthuis introduces statistical methods to evaluate findings.

Systemic LE and other systemic collagen diseases dis- One of the greatest increases in our perception of the tinguish themselves from all other autoimmune disorders scope of connective tissue diseases in recent years has by the multiplicity of the autoantibodies found. Although come with the development of our understanding of the single groups of clearly defined autoantibodies serve to SS-A(Ro) and SS-B(La) antibody systems, particularly characterize such autoimmune diseases as pemphigus from the viewpoint of their clinical relevance in such vulgaris, pemphigus foliaceus, and bullous pemphigoid, conditions as subacute cutaneous LE, Sjogren’s syn- collagen diseases, most notably systemic LE but also other drome, neonatal lupus, and other more or less related systemic connective tissue diseases, cliff er completely disorders. Zappi and Sontheimer (the group that first from the immunologic standpoint.’ In the spectrum from described subacute cutaneous LE) provide new insights cutaneous to systemic LE, we find what appears to be an not only into the clinical relevance of these antibodies but infinite variety of immunologic abnormalities. The con- trast in these forms of autoimmunity is paralleled by a

also into the basic biochemical nature of the antigens to which they are directed and their molecular biology.’

0 1993 by Elsevier Science Publishing Co., Inc. l 0738-082x/93/$6.00 387

388 BEUTNER

The availability of an increasing number of tests, par- ticularly for immunologic abnormalities of connective tissue diseases, pose challenging questions for dermatolo- gists. No one of the tests reveal laboratory abnormalities that occur in all cases of any subset of LE or other connec- tive tissue diseases, and no one of them is entirely disease specific. This perplexing diversity of clinical f?ndings and laboratory abnormalities points to the need for criteria for the classification of at least the major forms of cutaneous LE and of systemic LE cases with cutaneous manifesta- tions. Analyses of data on such forms of LE by methods of the type used for the development of the now widely accepted revised criteria for the classification of systemic LE of the American Rheumatism Associations reveal that dermatologists need a somewhat different set of criteria.9 Like the preliminary criteria for rheumatologists,1° the dermatologic criteria for LE may be regarded as being preliminary.

Diagnostic Criteria Dermatologic criteria for LE, as indicated by the analyses reported by the contributors to this issue, show that labo- ratory tests do afford more sensitive and more specific markers for the classification of both cutaneous LE and systemic LE cases with skin lesions than do the clinical signs of these conditions l*; but dermatologists do not treat laboratory test results or antibody titers-they treat patients. Thus, in the development of dermatologic cri- teria, particularly for systemic LE, a balance must be kept, between the specificity and sensitivity of the laboratory criteria on the one hand and the need for attention to the more elusive but more relevant clinical findings on the other.

Returning to a historic perspective, convincing evi- dence for an immunologic basis for scleroderma has be- come available only within the last two decades, as may be seen in the review of recent advances presented by Stephania Jablonska and her associates in Warsaw, Po- land.12 Jablonska, who has written several books on the subject, affords a truly incisive and up-to-date review of the subject. Even more recent is the recognition of the clinical entity of scleroderma/polymyositis overlap or scleromyositis and its relation to the Jo-l antibodies, re- viewed in this issue by the same group.13 As Dubois14 pointed out, with each new finding of immunologic or other laboratory abnormality in systemic LE, the scope of the disease and the number of cases increase. This now also holds true for scleroderma and other connective tis- sue diseases.

Conclusions Although no one person can hope to know everything about collagen diseases and no one monograph can cover

Clinics in Dermatology 1993;10:387-388

the subject comprehensively, such an issue as this one provides knowledgeable practitioners with a better un- derstanding of the origin and direction of some of the key developments in studies on collagen diseases.

ERNST H. BEUTNER, PhD

References 1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

11.

12.

13.

14.

Lahita RG. Overview of Lupus Erythematosus. Clin Der- matol 1993;10:389-392. Miescher PA, Fauconnet M. L’absorption du facteur “L.E.” par des noyaux cellulaires isoles. Experientia 1954;lO: 252-4.

Miescher PA, Tucci A. Historical perspectives of collagen diseases. Clin Dermatol 1993;10:393-397.

Beutner EH, Cunningham R, Chorzelski TP. Pathologic and physiologic autoimmunity and the autoimmune repair mechanism. In: Immunopathology of the skin. 3rd ed. New York: Wiley, 1987: Chapter 7.

Blaszczyk M, Jablonska S, Chorzelski TP, et al. Clinical relevance of immunologic Endings in cutaneous lupus ery- thematosus. Clin Dermatol 1993;10:399-406.

Velthuis PJ, Kater L, Baart de la Faille H. Direct immunoflu- orescence patterns in clinically healthy skin of patients with collagen diseases. Clin Dermatol 1993;10:423-430.

Zappi E, Sontheimer R. Clinical relevance of antibodies to Ro/SS-A and La/SS-B in subacute cutaneous lupus erythematosus and related conditions. Clin Dermatol 1993;10:431-441.

Tan EM, Cohen AS, Fries JF, et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Ar- thritis Rheum 1982;25:1271-7.

Jablonska S, Blaszczyk M, Beutner EH, et al: Studies on criteria of the European Academy of Dermatology and Venerology for the classification of cutaneous lupus ery- thematosus. II Preliminary dermatologic 1st step criteria for LE and 2nd step criteria for SLE. Int J Dermatol (in press).

Cohen AS, Reynolds WE, Franklin EC, et al. Preliminary criteria for the classification of systemic lupus erythemato- sus. Bull Rheum Dis 1971;21:643-8.

Beutner EH, Jablonska S, White DB, et al. Dermatologic criteria for classifying the major forms of cutaneous lupus erythematosus: Methods for systematic discriminant analy- sis and questions on the interpretation of findings. Clin Dermatol 1993;10:443-456. Jablonska S, Blaszczyk M, Chorzelski TP, et al. Clinical relevance of immunologic findings in scleroderma. Clin Dermatol 1993;10:407-421.

Jablonska S, Chorzelski TP, Blaszczyk M, et al. Sclero- derma/polymyositis overlap syndromes and their immuno- logic markers. Clin Dermatol 1993;10:457-472.

Wallace DJ, Dubois EL. Dubois’ lupus erythematosus. 3rd ed. Philadelphia: Lee & Febiger, 1987.