C a s e r e p o r l s

Generalized elastolysis associated with systemic lupus erythematosus Henry W. Randle, M.D., Ph.D., and Sigfrid Muller, M.D. Rochester, MN

A case of postinflammatory generalized elastolysis is reported in a patient having systemic lupus erythematosus, A review of the literature has pointed out the diversity of the disorder resulting in curls laxa, and a summary classification of the cases reported to date is included. We have emphasized the role of inflammation artd possible immune destruction of elastic fibers in acquired elastolysis. (J AM ACAD DERMA'rOL 8:869-873, 1983.)

Elastolysis is a disorder in which there is a de- crease or disappearance of elastic fibers from the dermis, with resultant wrinkling of the skin. This may be localized, as in blepharochalasis or anetoderma, or generalized, with the sagging, re- dundant folds of generalized elastolysis (cutis laxa) with its characteristic senile or aged facial appearance and involvement of internal organs.

There are inherited and acquired forms of elas- tolysis. The pathogenesis of each form is poorly understood. Some of the congenital forms may exhibit an enzyme deficiency resulting in poor elastin cross-linking. The generalized acquired form is very rare, with fewer than thirty cases being reported, The etiology of this form is also unknown, but it is frequently preceded by an in- f lammatory skin reaction.

We report the case of a patient with acquired postinflammatory, generalized elastolysis associ- ated with systemic lupus erythematosus. Cutane- ous biopsies /'or immunofluorescence revealed deposit ion of immunoglobulins in the dermis, in- dicating that our patient possibly had an acquired autoimmune mechanism resulting in the destruc- tion o f the elastic fibers and cutis laxa. A review

From the Department of Dermatology, Mayo Clinic and Mayo Foundation.

Reprint requests to: Dr. H, W. RandIe, Scott and White Clinic, 2401 South Thirty-First St., Temple, TX 76508/817-774-2I 11.

of the reports in the literature of acquired elas- tolysis suggests that immune destruction of elastic fibers may be the pathogenetic mechanism in other instances.

CASE REPORT

This 41-year-old woman began developing polyar- thralgias in 1971 and was diagnosed as having systemic lupus erythematosus (LE) on the basis of a positive LE clot and antinuciear antibody (ANA) test. Subse- quently, in 1974, she developed lupus nephritis, with decreased serum complement, elevated anti-N-DNA, and elevated serum creatinine. She received systemic corticosteroids for this intermittently for several years. In 1978, she began developing fine wrinkling of the skin on the face, extremities, and upper trunk, with a subsequent loss of tone and sagging of the skin, which had been progressive over the preceding 2 years (Figs. 1 and 2). The wrinkling had always been preceded by red, annular-macular lesions.

She had an associated subluxation of the finger joints, subconjunctival hemorrhage with sclerosing keratitis, easy bruising while on prednisone, Wolff- Parkinson-White syndrome, and exertional dyspnea. Her family history was negative for lupus erythemato- sus or any skin disorder. Her rather was said to have died of "emphysema" at the age of 74.

Laboratory studies included a hemoglobin of 10 gm/dl, creatinine, 1.7 mg/dl, normal serum glutamic oxaloacetic transaminase (SGOT) and alkaline phospha- tase, albumin, 1.81 gm/dl, positive LE clot, ANA, 1: 128-mixed pattern, anti-N-DNA, 6.26 mg/ml, CHS0,

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870 Randle and Muller

J o u r n a l o f the A m e r i c a n A c a d e m y o f

D e n ' n a t o l o g y

Fig. 1. A, Patient in 1975, at the age of 36. B, Patient in 1979, at the age of 40. C, One year later, in 1980, at the age of 41.

;,,i ~ 4.:.K/;~' ' ~:~ i ' : : .i ; 4 ;~ .~Jaml // / ;', % 2 ; ! ; [ / . ::2{'/;}, ~c. : = 4 : . N,:!:

' [ [ W ~ ~ ~ " e !r, .; ~ . ~ ?,e; . : , ;e~.

Fig. 2. Demonstrating the fine wrinkling of the skin at the (A) antecubital fossa and (B) knees.

15 units (41-90), C3, 33 mg/dl (88-252), C4, less than 7 mg/dl (30-80), serum copper, 66 mg/dl (75-145), serum zinc, 75 mg/dl (75-140), and c~-l-antitrypsin, 312 mg/dl (180-244). A skin biopsy revealed a marked decrease in the number of elastic fibers. A cutaneous biopsy for direct immunofluorescence was performed using fluorescein-labeled goat antihuman conjugates of IgG, IgA, IgM, C3, and fibrin. This biopsy revealed granular IgM at the basement membrane and granular staining IgM in the papillary dermis deposited on the elastic fibers (Fig. 3). Indirect epidermal fluorescent antibodies and basement membrane antibodies were negative.

DISCUSSION

Acquired elastolysis, as in our patient, becomes manifest later in life, usually after puberty or dur- ing middle life. In many cases, a stage of gen- eralized, inflammatory eruption may precede the development of the loose, cutaneous changes. These conditions include erythema multiforme, al- lergic reactions to penicillin, urticaria, vesicular eruptions, erythema perstans, and insect bites. Some show evidence of immune deposition in the skin, as in our patient. This form is not inherited, and, like the congenital forms, it may be associ-

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Elastotysis with SLE 871

ated with internal abnormalities or it may be lo- calized to the skin.

Inflammation has been reported in all types of elastolysis, including anetoderma (also known as macular atrophy): urticaria in the Pellizari type and red papules in the Jadassohn type.~ Secondary anetoderma may develop in the inflammatory conditions of lupus erythematosus, sarcoklosis, syphilis, tuberculosis, leprosy, and acrodermatitis chronica atrophicans/ Kossard and colleagues, in 1979,:1 reported a case of macular atrophy which was preceded by erythematous, macular or urticar- ial lesions in which immunofluorescent studies disclosed C3 localized to the elastic fibers. The patient had no other diseases. It was suggested by the authors that this localized form of elastolysis was due to an inflammatory condition caused by deposition of immunoglobulins and complement in the skin.

Patients with the entity "postinflammatory elas- tolysis and cutis laxa," which appears to be intern-tediate between localized and generalized elastolysis (PECL), were said to develop a fine wrinkling of the skin, following urticarial or annu- lar erythematous papular lesions which were thought to be due to arthropod bites.4'~ Direct im- munofluorescence had not been performed on these patients.

A patient with wrinkled spots several centime- ters in diameter on the breasts and eyelids was classified as having dermatochalasis circum- scripta. 6 The wrinkling was preceded by redness and swelling.

Convit and colleagues,7 in 1973, reported a case of localized elastolysis which started after succes- sive injections of Mitsuda antigen and a bacille Calmette-Gugrin (BCG) vaccine. Inflammatory lesions developed at the site of the lepromin test (Mitsuda antigen) and over 20 years progressed to large, hanging, baglike folds of skin in the axilla. Convit and colleagues suggested that this might be an autoimmune disease, and the disease showed a favorable response to the corticosteroids and other immunosuppressive agents.

Twelve of the twenty-six reported cases of generalized elastolysis were said to have been pre- ceded by infammation. It is in this last group that our patient can probably be classified. Reed and

Fig. 3. Direct immunofluorescence of lesion on the left ,arm showing (A) granular igM at the basement mem- brane and (B) granular staining IgM in the papillary dermis involving the elastic fibers.

colleagues s stated that "any active autoimmune process can be eliminated as a possible e t io logy ," but our patient developed a generalized elastolysis 7 years after she was diagnosed as having systemic lupus erythematosus. When she developed lax skin, it was always preceded by an inflammatory reaction, and cutaneous biopsies of these areas showed a deposition of immunoglobulins in the dermis in the areas of elastic tissue. This suggests to us that the immune deposits might have been responsible for the destruction of the elastic tissue. Direct immunofluorescence has rarely been per- formed in other reported cases of generalized elas- tolysis to see if it would account for the inflamma- tory reaction observed clinically. Deposition of immunoglobulins of elastic fibers could provide a chemotactic stimulus to macrophages, and IgM is capable of activating complement. The presence of immunoglobulin and, specifically, IgM in our

872 Randle and Muller

Journal of the American Academy of

Dermatology

T a b l e I . Classif icat ion o f elastolysis*

T~pe

I. Elastolysis A. Localized

i. Anetoderma

a. Primary (1) Inflammatory

(2) Noninflammatory

b, Secondary

2. Blepharochalasis

3. Dermatochalasis circum- scripta

4. Dermohypoderrnitis

B. Intermediate

1. Postinflammatory elasto- lysis and cutis laxa (PECL)

Generalized etastolysis

Congenital a. Genetic

( l ) AutosomaI domi- nant

(2) Autosomal reces- sive

(3) X-linked

b. Acquired

C.

1.

2. Acquired a. Postinflammatory b. Idiopathic

II. Pseudoelastolysis A. Neurofibromatosis B. Pseudoxanthoma elasticum

C. Senile or actinic skin D. Ehlers-Danlos

E. Leprechaunism F. Acrodemlatitis chronica

atrophicans

Comments

Elastic fibers become fragmented, disorganized, and fewer in number a~ Localized defect in the elastic tissue of the dermis ~ Well-circumscribed area of soft, thin, and wrinkled skin; internal organs

are free of conspicuous abnormalities ~ Lesions appear without any preceding recognized disorder 1 Pellizari type--preceded by urticarial; Jadassohn type--preceded by

red papules ~ Schweninger-Buzzi type- -somet imes preceded by ill-defined ery-

thema ~ Similar lesions may follow the skin involvement of inflammatory dis-

eases such as syphilis, sarcoidosis, and tuberculosis ~ The dermal laxity is localized to the periorbital regions; there is a fa-

milial tendency, but similar changes can occur in the acquired condi- tions of solar elastosis and senile elastotic degeneration ~z

Single case report of a young woman with thin, wrinkled spots on the breasts and eyelids, several centimeters in diameter, with multiple, fine telangiectasias, preceded by redness and swelling ~

Case report of a young man who had localized atrophic skin several cen- timeters in diameter which progressed slowly to a hanging, baglike fold in the site of a previous BCG and Mitsuda test 7

Clinical features are intermediate between localized and generalized elastolysis

Fine wrinkling with little loose folds, usually confined to the neck, shoulders, arms, face, and trunk; lacks internal involvement 4'~

Widespread, large, loose folds of pendulous, redundant inelastic skin, usually with internal involvement la

Appears in the newborn period t4 Determined genetically 14 Primary cutaneous involvement with a good prognosis ~5

Often accompanied by severe internal complications and early death a'~

Skeletal abnormalities and genitourinary tract abnormalities are prom- inent 14

Case report of an infant whose mother was taking penicillamine; condi- tion resolved within a few months of delivery t~

Acquired with no apparent inherited pattern ~a Fine wrinkling seems to be a prominent feature of this group ~ No unifying features t3 Conditions that may resemble elastolysis ~3 Elasticity is normal; presence of fibromas and caf~ au lait spots TM

Yellow plaques on the sides of the neck and large body folds; spares the face 16

Associated actinic changes with history of years of sun exposure TM

Originally called "cutis laxa"; increased elasticity with pseudotumors on the elbows and knees; elastic fibers are normal ~"

Folded loose skin is thickened and not lax: facies are characteristic ~7 Early inflammation followed by atrophic skin with reduction in both col-

lagen and elastic fibers ~a

*We are including this table because we have found it useful in studying these patients and tile reports in the literature of this diverse disease group.

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Elastolysis with SLE 873

pat ient suggests an au to immune role in the de-

s truct ion of the elastic fibers. The immune mech- an i sms could have been act ivated b y the systemic lupus erythematosus , as in our case , leprosy as in other cases, or o f an idiopathic basis, as in the

case o f macular a t rophy reported b y Kossard and col leagues.a

Jus t as there are a variety of clinical patterns of cutis laxa, there may be several possible causes. There is no standard classification for elastolysis (Table I).

In 1965, Goltz et al 9 suggested there might be a

dis turbance in the activity in the serum elastase inhibi tor o f patients with elastolysis , such as o~- 1-antitrypsin. A relative or absolute deficiency of

ant i t rypsin could allow the natural proteolysis of elastic tissue to proceed in an uncontrolled fash- ion. However , the c~-1-antitrypsin level in our pa-

tient was actually above normal. Elastolysis may not a lways be a p rob lem of degradation of elastic t issue, but one of synthesis. The earty stages of synthesis of elastic tissue are controlled, in part, by the enzyme lysyl oxidase . The activity of this e n z y m e was not measured in our patient. Lysyl

ox ida se is a copper-dependent enzyme. There was a s l igh t decrease in the serum copper in our pa- tient. The significance of this is not known. An

infant with generalized elastolysis was born to a mo the r who took penicil lamine throughout her p regnancy . ~~ Penicil lamine is a known copper

chela tor , which might be expected to produce pe- r iods o f low blood copper content in the fetus, thus inducing elastic tissue abnormali t ies . Our patient did not receive this or a s imilar medication.

T h u s , cutis laxa is a diverse disease. There is ev idence that many acquired cases develop follow- ing an inflammatory condition. Some of this inf lammat ion may be secondary to the deposition of i m m u n e globulins on the elastic fibers, as in our pat ient . In such cases, perhaps more specific ther- apy should be directed against the autoimmune disorder . This would be important since, at pres- ent, only surgical removal of redundant skin is ava i lab le to correct the cutaneous abnormalities

found in cutis laxa, and there is little that can be

done when systemic marfifestations deve lop and lead to death f rom pu lmonary e m p h y s e m a , heart failure, o r aortic rupture.

REFERENCES

1. Moschella S, Pillsbury D, Hurley H: Dermatology. Philadelphia, 1975, W. B. Saunders Co., vol. 2, pp. 960-995.

2. Deluzenne R: Les an6toderm/.es maculeuses. Ann Der- matol 83:618-630, 1956.

3. Kossard S, Kronman K, Dicken C, Schroeter A: Inflammatory macular atrophy: lmmunofluoreseent and ultrastruetura[ findings. J AM ACAD DERMATOL 1:325- 334, 1979.

4. Marshall J, Heyl T, Weber H: Postinflammatory elas- tolysis and cutis laxa. A report on a new variety of this phenomenon and a discussion of some syndromes characterized by elastolysis. S Afr Med J 40:1016-1022, 1966.

5. Verhagen A, Woerdeman M: Postinflammatory elas- tolysis and cutis laxa. Br J Dermatol 92: 183-190, 1975.

6. Uttendorfsky-Van Der Patten H: Dermatochalasis cir- cumscripta. Dermatologica 156:316-318, 1978.

7. Convit J, Kerdel F, Goihman M, et al: Progressive, at- rophying, chronic granulomatous dermohypodermitis. ,~'ch Dermatol 107:271-274, 1973.

8. Reed W, Horowitz R, Beighton P: Acquired curls laxa. Arch Dermatol 103:661-669, 1971.

9. Goitz RW, I-Iult AM, Goldfarb M, Gorlin RJ: Cutis laxa. Arch Dermatol 92:373-387, 1965.

10. Linares A, Zarranz J, Rodriguez-Alarcon J, et al: Revers- ible curls laxa due to maternal D-penicillamine treatment. Lancet 2:43, 1979.

11. Hult M, Goltz R, Midtgaard K: The dermal elastic fibers in cutis hyperelastica (Ehlers-Danlos syndrome) and in cutis laxa (generalized elastolysis). Acta Derm Venereol (Stockh) 44:415-420, 1964.

12. Beighton P, Bull J, Edgerton M: Plastic surgery in cutis laxa. Br J Plast Surg 23:285-290, 1970.

13. Harris R, Heaphy M, Perry H: Generalized elastolysis (cutis laxa). Am J Med 65:815-821, 1978.

14. Byers P, Siegel R, Holbrook K, et ai: X-linked cutis laxa--defective cross-link formation in collagen due to decreased lysyl oxidase activity. N Engl J Med 303:61- 65, I980.

I5. Agha A, Sakati NO, Higginbottom MC, et al: Two forms of cutis laxa presenting in the newborn period. Acta Paediatr Scand 67:775-780, 1978.

16. Fitzpatri.ck RB, Eisen AZ, Wolff K, et al: Dermatology in general medicine, ed. 2. New York, 1979, McGraw Hill Book Co., pp. 688-1217.

17. Roth $1, Schedewic HK, Herzberg VK, et al: Cutaneous manifestations of leprechaunism. Arch Dermatol 117: 531-535, 1981.