Journal of the

American Academy of
Tan-Lira and Bystryn Dermatology

native or adjunctive therapy in problem cases of pemphigus. munoadsorption: comparison of single versus combination
Dermatologica 1984;168:219-23. chemotherapeutic agents. Clin Exp Immunol 1978;34:32-
17. Guiilaume J-C, Roujeau J-C, Morel P, et al. Controlled 41.
study of plasma exchange in pemphigus. Arch Dermatol 23. Euler HH, Krey U, Schroder O, et al. Membrane plasma-
1988;124:1659-63. pheresis technique in rats: confirmation of antibody re-
18. Bystryn J-C. The therapy of pemphigus. Semin Dermatol bound. J Immunol Methods 1985;84:313-9.
1988;7:186-94. 24. Derksen RHWM, Schurman H J, Gmelilg-Meyling FHJ,
19. Ruocco V, Rossi A, Argenziano G, et al. Pathogenicity of et al. Rebound and overshoot after plasma exchange in hu-
the intercellular antibodies of pemphigus and their periodic mans. J Lab Clin Med 1984;104:35-43.
removal from the circulation by plasmapheresis. Br .I Der- 25. Cotterill JA, Barker D J, Millard LG. Plasma exchange in
matol 1978;98:237-41. the treatment of pemphigus vulgaris. Br J Dermatol 1978;
20. Guillot B, Donadio D, Guilhou J J, et zl. Traitement du 98:243.
pemphigus par les echanges plasmatiques. Sem Hop Paris 26. Johnson DW, Simon TL, Chapman WG. Pemphigus vul-
1980;62:1243-5. garis and plasma exchange. West J Med 1983;139:708-10.
21. Bystryn J-C, Schenkein I, Uhr JW. A model for the regu- 27. Shupack KH, Rock GA. Therapeutic plasma exchange. N
lation of antibody synthesis by serum antibody. Prog Engl J Med 1984;310:762-9.
Immunol 1971;1:627-36. 28. Hazards of apheresis [Editorial]. Lancet 1982;2:1025-6.
22. Terman DS, Garcia-Rinaldi R, Danneman E, et al. Specific 29. Jones JS, Dougherty J. Current status of plasmapheresis in
suppression of antibody rebound after extracorporeal ira- toxicology. Ann Emerg Med 1986;15:474-82.

Postinflammatory elastolysis and cutis laxa

A case report
Philip G. Lewis, MD, MPH,* Antoinette F. Hood, MD, Nancy K. Barnett, MD, and
Karen A. Holbrook, PhD Baltimore, Maryland, and Seattle, Washington

One of the rarest forms of curls laxa is postinflammatory elastolysis and curls laxa, a disease
previously reported only in children in Africa and South America. This disease is character-
ized by an urticarial or papular eruption followed by acute destruction of elastic tissue that
results in atrophy and severe disfigurement. It is distinguished from anetoderma and acquired
curls laxa by its clinical features, its occurrence in young children, and its relatively benign
course. This article describes the first case of postinflammatory elastolysis and curls laxa re-
ported in a white child from North America. (J AM ACADDERMATOL1990;22:40-8.)

Postinflammatory elastolysis and cutis laxa diameter, or erythematous papules that enlarge to
(PECL), a skin disease previously reported only in annular forms with a peripheral collarette of scale.
South American and African children, is character- The first cases were reported by Marshall et al. 1
ized by malaise, fever, and inflammatory skin lesions in 1966 in five children from South Africa. In 1974
that evolve into areas of atrophy, wrinkling, and Verhagen and Woerdeman 2 reported seven children
laxity. The initial skin lesions may occur in one of from Kenya with a similar disease. The first non-
two forms: large, urticaria-like lesions, 5 to 10 cm in African case was reported in Brazil by Ramos e
Silva 2 in 1969. All cases occurred in children of Af-
From the Department of Dermatology,The Johns Hopkins University rican or mixed Afro-Caucasian descent who were
School of Medicine, Baltimore, and the Department of Biological living in tropical or subtropical climates. To our
Structure, University of Washington. knowledge this is the first case reported in a child in
Accepted for publication Feb. 21, 1989. a temperate climate and not of African descent.
Reprint requests: Philip G. Lewis, MD, MPIt, Corporate Medical De-
partment, Rohm and Haas Company, Independence Mall West, CASE REPORT
Philadelphia, PA 19105.
*Now at the Corporate Medical Department, Rohm and Haas Com- The patient, the product of a full-term normal preg-
pany, Philadelphia. nancy, labor, and delivery, weighed 3200 gm at birth. His
16/1/12296 mother had a history of asthma and an allergy to penicil-
40
Volume 22
Number 1
January 1990 Postinflarnmatory elastolysis and cutis laxa 41

Fig. 1. Patient before illness.

Fig. 2. Face (A), neck (B), and buttocks (C) of patient after resolution of urticarial le-
sions.

lin. Both parents were reported to have normal skin. At age, with general anesthesic, he underwent a Bachelor-
6 months of age the patient was noted to have tight hip Brown arthrodesis of the right ankle to correct trauma-
adductor muscles. At 10 months of age he successfully induced arthritis. This procedure required the use of al-
underwent bilateral adductor tenotomies. At 5 years of lograft bone. Before surgery the patient had a normal
 Journal of thc
American Academy of
42 Lewis et al. Dermatology

Fig. 3. Photomicrograph of border of abnormal area shows loss of elastic fibers. (Acid or-
cein stain; X i00.)

urinalysis result, hematocrit of 38%, and a WBC count of negative or normat: serum protein electrophoresis; CBC;
7800 cells/ram 3. There were no problems during or im- urinalysis; determinations of levels of C3, C4, a-1-anti-
mediately after surgery; he required no blood transfu- trypsin, serum urea nitrogen, and creatinine; and tests
sions. On the sixth postoperative day a fever of 40 ~ C de- for ANA, heterophile antibody, and hepatitis B sur-
veloped, with mild pruritus and numerous urticaria-like face antigen. AST (SGOT) and ALT (SGPT) levels
lesions, 6 to 10 cm in diameter, on the extremities and were elevated to seven times normal, and the creatine
trunk. These lesions were erythematous and blanched on phosphokinase level was 12 times higher than normal
mild pressure. Mild diffuse swelling of the hands and feet values.
was present. There was no dyspnea or wheezing, and the Five months after the initial episode, in March 1981,
lungs were clear to percussion and auscultation. A chest the patient was admitted to The Johns Hopkins Hospital
x-ray film and electrocardiogram were normal. Other for examination. At that time his serum copper and cer-
laboratory studies included a hematocrit of 41% and a uloplasmin levels, results of pulmonary function tests, and
WBC count of 11,300 cells/ram 3, with 9% band forms, echocardiogram were normal. Skin and muscle biopsies
64% neutrophils, 4% eosinophils, and 23% lymphocytes. were done; the results are reported herein. Two years
Serum elastase inhibition was not measured. later, after several plastic surgery procedures with a gen-
The patient's skin lesions did not clear with diphenhy- eral anesthesic, he had a normal electrocardiogram,
dramine hydrochloride and ephedrine. A throat culture echocardiogram, and chest x-ray film, and normal serum
was obtained to rule out streptococcal infection, and the copper and ceruloplasmin levels. The creatine phosphoki-
patient was treated with erythromycin. Antihistamines nase level was still two times higher than normal values.
were continued. His fever remitted after 4 days, and the Reexamination in 1987, 5 years after the original event,
erythromycin was discontinued when a negative culture showed normal pulmonary and cardiac function and no
was determined. Acetaminophen had been given in place change in his skin lesions since 1982.
of aspirin. The patient's urticaria-like lesions persisted, Histologie examination. A biopsy specimen of one of
however. the atrophic cutaneous areas showed a decreased number
During the next 2 months the original lesions gradually of pilosebaceous units and a decrease in the thickness of
resolved and left atrophic, wrinkled areas (Figs. 1 and 2). the reticular dermis. Acid orcein staining showed marked
There was extensive wrinkling of the face and loss of the diminution in the number of elastic fibers in the reticular
normal skin tone, producing a "bloodhound" appearance. dermis (Fig. 3). The fibers that were present were short-
Throughout this period crops of smaller, 5 to 10 mm le- ened and fragmented, but the collagen appeared normal.
sions continued to develop, which, in contrast to the larger No inflammatory cells or alterations in the number of fi-
lesions, cleared after the administration of antihistamines broblasts were observed. A skin biopsy specimen of a
and left no residual atrophy or wrinkling. Two months clinically normal area showed no abnormalities. Addi-
later the results of the following laboratory studies were tional histologic observations of lesional skin from the
Volume 22
Number l
January 1990 Postinflamrnatory elastolysis and cutis laxa 43

~ j T/.
~-~r , ~; .... ...... ,.,, .,. . ,

~....... ...... ~'~-.e:.,~ r 9 ~ ~": - . . - ~ . .

,.. ~ ,, ~ 9 ~" "-',.,'~ !~

.
...... .~ "~ .r . o ::e~,~, -; f ' - .1[
~):.. ! -.,:..~. .. , '.: .. ,~ ~..'-~"~ ,
' " " "

' ~-~Z'~-'~-'-~-'t r. ~ ." .

Fig. 4. Electron micrographs oflesional site of dermis. Note normal shape and diameter of
collagen fibrils (A and B) but absence of mature elastic fibers at boundaries of collagen fiber
bundles (A to C). Arrows indicate normal position of elastic fibers. C, Sparse amount of elas-
tin matrix (E) is associated with small bundle of microfibrils. (A, • B, • C,
• 19,000.)

trunk and eyelid and uninvolved skin were made of 1 #m quently to 100% propylene oxide and were infiltrated with
sections prepared from plastic-embedded samples stained increasing concentrations of plastic embedding medium
by the method of Richardson et al.3 Data from these ob- (Epon) up to 100%,5 The samples were polymerized in a
servations confirmed that, in both normal and affected 60 ~ C oven overnight and were then oriented for section-
regions of the skin, the collagen fiber bundles appeared ing. Semithin (1 pro) and thin (800 A) sections were pre-
normal in size and structure, but in the lesional tissue the pared for light microscopy and electron microscopy,
borders of the bundles normally occupied by large, respectively. The thin sections were stained with saturated
densely staining elastic fibers contained only finely fila- uranyl acetate, lead citrate, and 1% phosphotungstic acid
mentous and diffuse material. and were examined under a Philips 420 S (T)EM electron
A muscle biopsy specimen showed a random increase microscope (Philips Electronic Instruments Inc., Mah-
in muscle fiber size. Marked fibrous and fatty degenera- wah, N.J.) in the transmission mode. 6
tion typical of the Duchenne type of muscular dystrophy Examination of lesional skin from the trunk revealed
was also present. large collagen fiber bundles that contained fibrils of nor-
Electron microscopic examination. Biopsy specimens mal diameter. The space between the bundles showed
from affected (trunk and eyelid) and unaffected (trunk) abundant diffuse material (presumed to be proteoglycans
skin were fixed in Karnovsky's fixative.4 The specimens and filamentous glycoproteins), fibroblastic cells, and a
were washed in 0.2 mol/L sodium cacodylate buffer and sparse amount of microfibrillar material, some of which
postfixed in 1% OsO4 in distilled water. The tissues were was associated with a small amount of elastic matrix (Fig.
then washed and dehydrated through a series of alcohols 4, A to C). In a tissue sample from the eyelid, changes
increasing in concentration to 100% ethanol and subse- were noted in both collagenous and elastic connective tis-
 Journal of the
American Academy of
44 Lewis et al. Dermatology

Fig. 5. Electron micrographs of dermis from eyelid. Note diffuse matrix material integrated
within bundles of collagen fibrils, A, and unusual packing of clusters of small-diameter fibrils
(small arrows). B, Abundant elastin microfibrils are apparent (large arrows), and in some
portions of accumulations, elastin (E) is also evident. (A, • 12,600; B, •

sue. The diameter of collagen fibrils varied within the DISCUSSION

bundles. Tightly packed clusters of small-diameter fibrils
This case and the syndrome it represents are sig-
were surrounded by more loosely organized fibrils of
nificant in that they provide insight into the cause of
larger diameter (Fig. 5, A). Bundles of elastic microfibrils
were evident at the borders of the collagen bundles, and elastic tissue and hypersensitivity disorders. Al-
a small amount of elastin was recognized in some of these though our ability to classify specifically our pa-
(Fig. 5, B). In several areas the fibrous connective tissue tient's illness as a true example of the P E C L
appeared to be embedded in a large amount of diffuse syndrome is hampered by the absence of reliable
material (Fig. 6, A and B). markers for any of the alternative elastic tissue syn-
Volume 22
Number 1
January 1990 Postinflammatopy elastolysis and cutis laxa 45

Fig. 6. Electron micrographs of elastic fibers in dermis of nonlesional skin. A, Normal-

appearing elastic fibers are evident. B, Fibers show regions where elastin matrix (E) appears
disorganized and fiber is embedded in considerable amount of diffuse connective tissue ma-
trix. (A, X7440; B, X8370.)

dromes, the age of the child and the sudden occur- known (Fig. 4, B). Some evidence indicates that
rence of fever, malaise, and large urticaria-like these problems are coincidental. For example, the
lesions with subsequent resolution and elastic tissue pathologic findings of the muscle suggest a chronic
damage certainly seem to place this case among dystrophy, not a disease of recent onset.
those described by Verhagen and Woerdeman. 2 It might be argued that this child's illness is sim-
Some disparities exist, however (Table I and Fig. 4, ilar to that of the children described by Wanderer et
A). The associated abnormalities of bone and mus- al., 7 Muster et al., 8 and Kerl et al., 9 who had wide-
cle noted in the child are not common to the previ- spread elastic tissue damage of sudden onset and as-
ously reported cases, and their significance is un- sociated systemic involvement. Such a similarity
 Journal of the
American Academy of
46 Lewis et al. Dermatology

Table I. Comparison of characteristics of PECL Table II. Proposed classification of cutis laxa
syndrome with those of our case syndromes
I Nature ofsyndron~
Prodromal fever + + Lesions Congenital Acquired
Large, urticaria-like lesions + +
with resultant atrophy Cutaneous only Autosomal dominant PECL
Small, recurrent urticarial + + Systemic and Autosomal recessive PECL-S
lesions with no atrophy cutaneous or X-linked recessive
Erythematous papules with + - PECL, Postinflammatory elastolysisand cutis laxa; PECL-S, systemic
resultant atrophy postinflammatory elastolysis and cutis laxa.
NeutrophUic infiltrate in + *
acute lesions
E~inophilia + -
Destruction of elastic fibers + + ance and disappearance and the lack of progression
Age at onset 1-9 yr + + of the lesions, and from those described by LeBoit et
Family history - - al. 12 in the lack of epidermotropism and/or a gran-
Systemic involvement - -+-1 ulomatous infiltrate and progresion to cutaneous
African descent + -
lymphoma. Differentiation from Ehler-Danlos syn-
+, Pr~ent; - , absent; PECL, postinflammatory elastolysis and cutis drome, Marfan syndrome, and pseudoxanthoma
laxa. elasticum can be made on the basis of family history,
*Because our patient did not have an acute lesion, we can only specu-
late as to the presence or absence of neutrophils at the early stage of lesion morphology, and histopathologic and electron
systemic PECL (PECL-S) developments. microscopic differences in elastic and collagen fiber
tit is not clear whether the muscular changes noted in this case were in abnormalities, and on the basis of the lack of other
any way related to the process that produced skin changes.
classically associated clinical abnormalities (Table
III). The most difficult point of differentiation is be-
suggests that these children's disease may represent tween PECL and other cutis laxa syndromes (Table
a second form of PECL, one that is associated with IV).
significant but limited systemic involvement. Such a There are similarities between PECL and the
syndrome might be termed PECL-S and would fit other forms of cutis laxa. All have no significant vis-
well in the classification scheme presented in Table ible changes on hematoxylin-and-eosin staining and
II. To date, our patient has had no extracutaneous a granular degeneration of elastic tissue on acid or-
involvement except for the muscle inflammation, cein staining. On electron microscopic examination
which appears to be a problem of the Duchenne type the changes in the connective tissue components in
that is unrelated to the elastic tissue destruction. patients with inherited forms of cutis laxa are highly
Determining whether the present case fits into the variable. Generally, however, they are consistent
PECL-S syndrome, as opposed to PECL, however, with a defect in the synthesis and assembly of the
is difficult. elastic fiber rather than with a degradative
The greatest doubt about this and the other phenomenon.13 It is difficult to interpret the changes
examples of P E C L is that they may be instances of in the elastic fibers in our patient because the biopsy
a previously described syndrome. The expanding samples were obtained from late-stage lesions. The
papular lesions of P E C L resemble erythema chroni- lesional tissue does not show evidence of degraded
cum migrans. Yet erythema chronicum migrans elastic fibers (i.e., frayed, granular, irregularly
clears without residual atrophic lesions or scarring shaped fibers, inflammatory cells, or macrophages
and may be associated with arthritis and central with phagocytic vacuoles)--all of which might be
nervous system dysfunction. P E C L may be distin- expected to result from an inflammatory process. 14
guished from anetoderma by its occurrence in a It is possible, however, that such observations would
younger age group and by the large size of the have been possible if tissue had been examined at an
lesions. In particular, our case appears to be different earlier stage in the lesion and that the observed lack
from those reported by Schweninger and Bruzzi 1~in of elastic fibers in the affected skin may be the con-
the age at onset and the lack of progression, from sequence of the fibroblasts' inability to synthesize
those reported by Fitz et al. 11 in the sudden appear- these fibers after the inflammatory flares. One won-
Volume 22
Number 1
January 1990 Postinflarnmatory elastolysis and cutis laxa 47

Table III. Comparison of P E C L with other similar clinical syndromes

Other syndromes

Erythema
chronieum Elder~Danlos Marfan Pseudoxanthoma
Characteristics PECL Anetoderma migrans syndrome syndrome elasrlcum

Age at onset (yr) 1-9 20-40 10-30 up to 40 up to 20 20-40

Female/male ratio 10:1 3:1 1:2 1:2 1:1 2:1
Genetic pattern None None None Autosomal Autosomal Autosomal
dominant dominant dominant
and recessive; and recessive
X-linked recessive
Extensive cutaneous + - _+ ___
involvement
Systemic involvement - - ++ +++ +++ +++
Inflammatory prodrome +++ ++ ++ -
Effect on collagen - + - +++ ++ ++
Effect on elastic tissue +++ +++ - ++ ++ +++
--, Absent. Symbols +, ++, and + + + indicate likelihood of occurrence in any individual case of this syndrome.

ders, however, why after the acute inflammatory Table IV. Comparison of P E C L with other cutis
phase the fibroblasts from adjacent normal tissue do laxas
not repopulate the lesional sites and eventually Other
ameliorate the condition. PECL curls laxas
On electron microscopic examination the other
forms of cutis laxa show elastic fibers that are denser Family history - +
Systemic involvement -- _
than normal, with increased elastin and many loosely Serum copper level Normal High or low
bound elastic fibrils. The collagen bundles are often Serum ceruloplasmin Normal Low
larger than normal and have an irregular level
diameter. 16 Normal areas in the other cutis laxa Serum elastase inhibitor Normal Low
syndromes show changes similar to those seen in af- level
fected areas but to a lesser degree. The electron mi- PECL, Postinflammatory elastolysis and cutis laxa.
croscopic findings of P E C L show a marked decrease
to a complete absence of elastic fibers but essentially
normal collagen fibers in the affected areas. Areas of crease in levels of serum elastase inhibitor modu-
clinically normal skin in P E C L appear normal by lated by a disturbance in copper metabolism. This
electron microscopy. The skin and systemic changes opinion is partly based on the observation that swine
in other cutis laxa syndromes are progressive and with decreased serum copper and normal cerulo-
eventually lead to death from emphysema and from plasmin levels have a decreased level of serum
aortic aneurysms in the second to fourth decades of elastase inhibitor; aortic aneurysms develop. Indeed,
life.15 Although the longest period of observation of some patients with congenital cutis laxa have been
P E C L patients is 8 years (5 years in our case), the found to have decreased levels of serum elastase in-
changes do not appear to be progressive. 2 Other dif- hibitor. Byers et al. ts noted that patients with
ferences between cutis laxa and P E C L are more in- X-linked recessive cutis laxa and decreased lysyl ox-
triguing and hint at the possible pathophysiology of idase levels also have decreased levels of serum cop-
cutis laxa syndromes. per. All this suggests the possibility that the changes
Patients with cutis laxa have shown low levels of in cutis laxa are manifestations of abnormal copper
serum oq-antitrypsin and ceruloplasmin and ele- metabolism.
vated serum and skin copper levels. 15 These levels The early lesions of PECL, which were not histo-
are normal in P E C L patients. Goltz et al. 17 postu- logically examined in our patient, show a high con-
lated that the changes in cutis laxa are due to a de- centration of neutrophils in the dermal infiltrate. 2 It
 Journal of the
American Academy of
48 Lewis et al. Dermatology

is likely that whatever abnormality of copper me- cular disease and cutis laxa following acute febrile neutro-
philic dermatosis. J Pediatr 1983;101:243-8.
tabolism exists in other cutis laxa patients is also 9. Kerl H, Burg G, Hashimoto K. Fatal pencillin-induced,
present to a lesser degree in patients with PECL, in generalized, post-inflammatory elastolysis (cutis laxa). Am
whom the disorder is not clinically evident. Under J Dermatopathol 1983;5:267-76.
normal circumstances the elastase inhibitor levels 10. Schweninger E, Bruzzi F. Internationaler Atlas von selte-
nen Hautkrankheiten. Leipzig: L Voss, 1891:part 5, plate
are sufficient to prevent elastic tissue damage. In the 15.
event of a massive hypersensitivity reaction with a 11. Fitz F, Venecie PY, Winkelman RK, et al. Anetoderma:
marked neutrophilic response, however, there may clinical findings, associations, and long-term foUow-up
evaluations. Arch Dermatol 1984; 120:1032-9.
be an extensive release of elastase. The ability of pa- 12. LeBoit PE, Zackheim HS, White CR. Granulomatous
tients with P E C L to produce elastase inhibitor is variants of cutaneous T-cell lymphoma: the histopathology
overwhelmed, and a subsequent loss of elastic fibers of granulomatous mycosis fungoides and granulomatous
results.19 slack skin. Am J Surg Pathol 1988;12:83-95.
13. Holbrcok KA, Byers PH. Structural abnormalities in the
dermal collagen and elastic matrix from the skin of patients
REFERENCES with inherited connective tissue disorders. J Invest Derma-
1. Marshall T, Heyl T, Weber HW. Post inflammatory tol 1982;79(suppl 1):7-16.
elastolysis and cutis laxa. S Afr Med J 1966;53:1016- 14. Braverman IM, Fonferko E. Studies in cutaneous aging. I.
22. The elastic fiber network. J Invest Dermatol 1982;78:434-
2. Verhagen AR, Woerdeman MJ. Post-inflammatory elas- 48.
tolysis and eutis laxa. Br J Dermatol 1975;92:183-90. 15. Reed WB, Horowitz RE, Beighton P. Acquired cutis laxa:
3. Richardson KC, Jarrett L, Finke EH. Embedding in epoxy primary generalized elastolysis. Arch Dermatol 1971;
resins for ultrathin sectioning in electron microscopy. Stain 103:661-9.
Technol 1960;35:313-23. 16. Nanko H, Jepsen LV, Zachariae H, et al. Acquired curls
4. Karnovsky MJ. A formaldehyde-glutaraldehyde fixative of laxa (general elastolysis): light and electron microscopic
high osmolarity for use in electron microscopy. J Cell Biol studies. Acta Derm Venereol (Stockh) 1979;59:315-24.
1965;27:137A-40A. 17. Goltz RW, Hult AM, Goldfarb M, et al. Cutis laxa: a
5. Lu ft JH. Improvements in epoxy resin embedding methods. manifestation of generalized elastolysis. Arch Dermatol
J Biophys Biochem Cytol 1961;9:409-14. 1965;92:373-85.
6. Reynolds ES. The use of lead citrate at high pH as an elec- 18. Byers PH, Siegel RC, Holbrook KA, et al. X-linked cutis
tron-opaque stain in electron microscopy. J Cell Biol laxa: defective cross-link formation in collagen due to
1963;7:208-13. decreased lysyl oxidase activity. N Engl J Med 1980;303:
7. Wanderer AA, Ellis ET, Goltz RW, et al. Tracheobron- 61-5.
chiomegaly and acquired cutis laxa in a child. Pediatrics 19. Janoff A. Mediators of tissue damage in leukocyte lysos-
1969;44:709-15. omes. X. Further studies on human granulocyte elastase.
8. Muster A J, Rharati S, Herman J J, et al. Fatal cardiovas- Lab Invest 1970;22:228-36.