The skin in systemic sc/erosis 
Review paper 
THE SKIN IN SYSTEMIC SCLEROSIS 
M.L. Cagnoni and T. Lotti 
ABSTRACT 
Systemic sclerosis is a systemic disease of unknown etiology which has both cutaneous and systemic 
manifestations. This disorder is often preceded or accompanied by Raynaud's syndrome. 
Patients affected by chronic systemic sclerosis may present many cutaneous manifestations like pigmentary 
changes and vascular lesions including panniculitis, erythema nodosum, livedo reticularis, atrophie blanche or 
ulcerations that are often indicative of a specific phase of the disease. 
In very rare cases systemic sclerosis may occur without any cutaneous symptoms, while more frequently 
patients present different pattern of cutaneous involvement. 
Cutaneous involvement has been divided into three groups: the first group is characterized by an 
involvement of acral regions, the second group includes disorders which start distally and the third group is 
characterized by generalized cutaneous sclerosis. 
KEY WORDS 
systemic sclerosis (SSc), skin, connective tissue. 
INTRODUCTION 
In this paper we discuss the most recent data 
concerning the affected skin in systemic sclerosis 
(SSc) as described in the recent issue of Clinics in 
Dermatology, reviewed by Lotti and Matucci-Cerinic. 
From the dermatological point of view patients have 
been divided into three groups according to the 
peculiar characteristics. 
acta dermatovenerologica A.P.A. Vol 4, 95, No 1 
A GENERAL REVIEW AND OUR 
OBSERVATIONS 
The first group includes over 50 % of the patients. 
Here the disease typically involves the skin of the 
acral portions of the extremities which show 
scleroatrophic lesions on the fingers and occasional!y 
also on the toes (sclerodactyly) (Fig. 1). The forearms 
and the face can be affected and gradually the 
upper extrernities can be involved. Frequently scattered 
13 
The skin in systemic sclerosis 
teleangiectasias are present, most often as stellate 
nevi on the face and upper chest. 
Fig. l. Indurated skin appearing shiny and taut with 
developing contractures 
In the second group the disease starts distally. 
Raynaud's phenomenon is observed and diffuse 
cutaneous sclerosis progresses centripetally with visceral 
and articular involvement (Fig. 2). Usually in this 
group no teleangectasias are evident. The scleroatrophic 
degeneration of the skin of the hands is usually 
preceded by a phase of fixed oedema which may 
last even months and which is followed by sclerodactyly 
and acrosclerosis. The skin of the face, of the 
forearms and of the upper portion of the chest is 
usually involved later ( 4). 
The third group is less frequent. It is characterized 
by the early involvement of the trunk and by the 
successive centrifuga! involvement of the extremities. 
This form is not necessarily preceded or accompanied 
by Raynaud's phenomenon, which is usually observed 
only in an advanced phase of the disease (5) . It can 
lead to a whitish sclerosis of the whole skin surface, 
which is sometimes characterized by single, diffuse, 
confluent sclerodermic lesions (generalized morphea) 
to which a great number of teleangectasias are 
associated. It can also lead to an involvement of 
viscera, joints and muscles. Mild fever may be 
present (4). Teleangectasias (stellate nevi, macular 
or linear) are present in 75% of the patients 
affected by SSc and formed by vessels of a diameter 
between 0.2-20 mm. They are mostly present on the 
face, the lips, the mouth, the upper trunk, the 
palms and on the back of the hands. They can also 
involve the thighs. 
In patients with acral cutaneous sclerosis (first 
group) the disease appears more often at a late 
14 
age; its course is relatively benign and serious 
visceral involvement is less frequent. Usually the 
onset of the disease is preceded by manifestations 
as fatigue, headache, depression, fever and by 
Raynaud's phenomenon. In most cases the acral 
cutaneous sites are first involved. Fingers and the 
back of the hands, and later on, other cutaneous 
sites as the forearms, the neck and the face, undergo 
a two-stage transformation. 
The first oedematous stage is characterized by 
oedematous swelling of the back of the hands 
( oedematous scleroderma) and by typical cyanosis of 
the fingertips with frequent loss of tissue. Such 
oedema is associated with morning fatigue, arthralgia 
and, occasionally, compression of the median nerve. 
The oedema may involve the arms, the face, and 
the trunk and is partially due to the deposit of 
hydrophilic glycosaminoglicans in the dermis. It can, 
however, also reflect a local inflammation, hydrostatic 
effects and microvascular alterations. It is stili not 
clear today what causes the regression of this oedema. 
Fig. 2. Presence of Raynaud's phenomenon: well-markated 
blanching of the digit on exposure to cold 
acta dennatovenerologica A .P.A. Vol 4, 95, No 1 
Ihe skin in systemic sclerosis 
The second, atrophic stage becomes evident at an 
advanced stage of the disease and is characterized 
by atrophy of the skin and fragility of the superficial 
dermis. The skin of the fingers, toes and the back 
of the hands is taut, thickened and shiny, resulting 
in a reduction of the flexion and extension movements 
(6). Modifications of the pigmentation of the fingers 
and of the back of the hands accompany these 
atrophic alterations, as do teleangectasias on the 
palms. Moreover, ulcerative phenomenon of bony 
eminences are frequent and may be correlated with 
the trophic alterations of the fingers. 
It has been seen that in this phase the total 
amount of collagen in the tissues is reduced whereas 
its density is normal (7). 
The nail bed is most often erythematous and 
occasionally teleangectasias which are visible with 
the naked eye are present. Frequently enough the 
cuticle appears dishomogeneous. The examination 
of the nail bed may show bleeding and capillary 
infarcts which are followed by scarring and atrophic 
processes and which may result in the formation of 
large avascular areas. The gradual loss of parts of 
the fingertips may be accompanied by necrosis and 
by gradual resorption, especially of the periungueal 
area (8-10). The scleroatrophic regions may show a 
typically "cobbled" skin resulting in discontinuous 
scarring, dyschromias, lymphangiectasias and sub-
cutaneous nodules ( 4). A palmar erythema on the 
tenar and hypotenar eminences may be characteri-
stically associated with these manifestations. 
In the serum of majority of these patients and in 
50% of the patients having so-called CREST syndrome 
(Calcinosis, Raynaud's phenomenon, Esophageal 
dysfunction, Sclerodactyly, Teleangectasia) anti-
centromere antibodies (ACA) are present (11). 
In the scleroatrophic areas typical little papules 
( deposits of amyloid substance) may be observed. 
In the patients belonging to the second group 
Raynaud's phenomenon usually closely precedes or 
even closely coincides with the onset of the disease. 
The cutaneous lesions extend rapidly involving the 
trunk and the arms ( 4). The incidence of clinically 
detectable pulmonary, renal or cardiac alterations is 
particular high. In some patients the hardening of 
the skin may be initially accompanied by a dark-red 
erythema. In many of these patients anti-topoisomerasis 
I autoantibodies are observed in the serum. 
The non-constant presence of anti-fibrillarine 
autoantibodies is peculiar to the third form of the 
disease, which characteristically implies widespread 
acta dermatovenerologica A .P.A. Vol 4, 95, No 1 
cutaneous sclerosis and a great number of tele-
angectasias (12). In most cases the cutaneous 
manifestations precede the visceral involvement by 
severa! years but the opposite may also occur. 
Chronic systemic sclerosis is sometimes accompanied 
by a panniculitis which is clinically not unlike erythema 
nodosum. In fact, it manifests itself with a transient 
oedema covering dermal and hypodermal nodules 
(13) . 
In patients with SSc "white atrophy" (whitish-
coloured scleroatrophic areas of vasculitis, sometimes 
striped for the presence of hyperchromic regions 
and crossed by teleangectasias) and "livedo reticularis" 
(skin erythematous, cyanotic and pigmented with 
reticular appearance) may arise on the lower third 
of the legs. At the site of the skin affected by 
"white atrophy" very painful ulcers may arise, which 
have little tendency to heal. These are caused partly 
by inflamrnation of the vessels and partly by mechanical 
phenomenons, namely compression by the sclerotic 
tissue (14) 
Calcinosis, present in approximately 25% of the 
cases, occurs on the fingers, on the extensor surfaces 
of the forearms, especially on the palmar side of 
the terminal phalangeas, and is more frequent in 
women. These calcium deposits may break and 
expel calcareous material. The re-epithelisation of 
such lesions is very slow. Typical alterations of SSc 
in its limited form are calcinosis with simultaneous 
resorption of the bone of the phalanges (15). 
Patients affected by SSc often show modifications 
of the pigmentation of the skin, most frequently on 
the face, on the lower third of the abdomen and on 
the thighs. These are probably expressions of post-
inflammatory pigmentary alterations of the sclerotic 
areas (16-17). In most cases such are hyper-
pigmentations arising in isolated areas of sclerosis. 
Occasionally they may even precede the cutaneous 
sclerotic manifestations; sometimes they may be so 
intense and widespread that they resemble Addison's 
disease without, however, involving the mucosae 
(18). Manifestations resembling acanthosis nigricans 
may be observed at the flexor sites (4). Areas of 
depigmentation may arise in different sites of the 
body, even simultaneously, which wholly resemble 
vitiligo from both the clinical and the immuno-
pathological standpoint (17). 
Another cutaneous manifestation typical of the 
!atest phase of systemic sclerosis is atrophy of the 
cutaneous appendages (pilo-sebaceous units, ducts 
and eccrine glands). Another is scleroderrnal (atrophic) 
alopecia on the scalp ( 4). 
15 
The skin in ;ystemic sclerosis 
In these patients affected by SSc, ivory-coloured 
subcutaneous nodules with diameter between 3-20 
cm are occasionally evident. These nodules prevalently 
arise on the trunk and thighs (19) and are 
hystologically characterized by the presence of fibrinoid 
necrosis and fibromatous alterations. 
THE FACE IN SYSTEMIC 
SCLEROSIS 
The face is one of the first areas to be hit by the 
disease. In fact, at the onset of the disease a loss 
of expressiveness is commonly noticed: the face 
becomes an inexpressive mask (facies sclerodermica) 
and there is loss of the normal facial lines. The 
face seems tense with a sharp nose and has reduced 
dimensions because tbe skin is tbinned and sclerotic. 
In an early oedematous phase a periorbital oedema 
can be observed in patients witb few otber cutaneous 
manifestations of SSc (20). Tbe skin of the forehead 
can no longer rise in folds and that of the nase 
becomes thin and translucid. The patient can hardly 
completely open his moutb wbich bas become smaller 
(microstomia). Tbe lips are thin and fixed folds are 
present near the upper lip which extend in a typical 
radia! way. The mobility of the eyelids is also 
reduced. 
Tbe sclerosis can successively extend to tbe neck. 
More rarely there is an involvement of the mucosae 
with a painful bardening of the gums and tongue 
(21). 
HYSTOLOGICAL ASPECTS 
The histopathological aspects of SSc vary according 
to the clinical stage. The epidermis may be normal 
(in the initial phases) or tbickened or atropbic 
(later pbases) witb loss of tbe papillary pattern. 
Initially tbe dermis is oedematous and present swelling 
of the collagen fibers which successively undergo 
homogenization. The non-homogenized fibers are 
thickened and extend parallel to tbe skin surface 
(22). 
In tbe first stage (inflammatory phase ), there is a 
perivascular infiltrate which is mostly constituted by 
lymphocytes and by cells of the monocyte/macropbage 
line as well as by T-helper lymphocytes which express 
the HLA-DR. However, no HLA expression is 
observed in the keratinocytes of the affected skin, 
as is, on the contrary, seen in graft versus host 
disease (GVHD) (23). An infiltrate is also present 
16 
among the collagen fibers of the dermis and the 
subcutaneous fat (septa). Here evidence of septal 
panniculitis with an infiltrate containing lymphocytes, 
plasmacells and eosinopbils can be observed (24). 
In tbis pbase tbe number of mastocytes bas increased 
(25). At the sites of the teleangectasias, the presence 
of immunoglobulins and of complement was shown 
by immunofluorescence (26). In sclerotic areas on 
the other hand, this test was negative. 
Successively the dermis thickens, and collagen 
fibrils become dense and sclerotic and lay parallel 
to the (derma-epidermal) junction. The number of 
fibroblasts is reduced and they are not easily 
identifiable (27) . The pilo-sebaceous appendages (but 
not the errector muscles of the hair) and the 
dermal and hypodermal adipose tissue progressively 
dwindle until they disappear completely. In the late 
sclerotic phase, homogenized connective tissue replaces 
areas of subcutaneous adipose tissue. Even the 
sweat glands tend to disappear; only a few remain 
deep in the sclerotic mass ( 4). 
In the sclerotic stage of the disease, in addition 
to the atrophy of the epidermis, to the hyalinisation 
of the collagen of the dermis and to the frequent 
loss of melanocytes, elastic tissue is also last. The 
skin vessels of the patients who have only Raynaud's 
phenomenon display histopathological alterations of 
varying degrees, wbicb are, however, not patho-
gnomonic: capillary and lymphatic congestion de-
pending on the cyanotic phase, thickening of the 
basal membrane and endothelial oedema (28-30) 
The capillaries of the affected skin have greatly 
reduced diameters, often leading to the occlusion of 
the lumen (31). 
The increase in tbe serum levels of both factor 
VIII von Willebrand, antigen and coagulant, which 
is not, however, constant, and of the angiotensin 
converting enzyme, is correlated to the vascular 
lesions. So is the increase of the cutaneous and 
plasma fibrinolytic activity (32-33). Such activity may 
be normal. 
Tbe finding of normal values may indicate that 
the endothelial-articular-cutaneous area is mostly 
involved in the process. In this area, in fact, no 
fibrinolytic activity is evident. On the other hand, 
the cutaneous fibrinolytic hyperactivity which has 
occasionally been observed in SSc could be associated 
with bypoxia in the post-capillary compartment, caused 
by the partial occlusion of the arterioles. 
acta dermatovenerologica A .P.A. Vol 4, 95, No 1 
The skin in systemic sclerosis 
REFERENCES 
l. Lotti T, Matucci-Cerinic M. Color Atlas. Sclero-
derma: from morphea to systemic sclerosis- The 
clinical aspect: Clinics in Dermatology. In: Elsevier 
ed. 1994; 12(2): 197-200. 
2. Jablanska S, Rodnan GP. Localized forms of 
scleroderma. Clin Rheum Dis 1979; 5: 215-41. 
3. Piette WW, Dorsey JL, Foucar E. Clinical and 
serological expression of localized scleroderma. J 
Am Acad Dermatol 1985; 13: 342-50. 
4. Braun-Falco O, Plewig G, Wolf HH, Winkelmann 
RK. Sclerodermas. In Sturtz H Wurzburg HG. eds. 
"Dermatology", Springer-Verlag, Berlin, 1991; 553-
62. 
5. Gifford RW, Hines EA. Raynaud's disease among 
women and girls. Circulation 1957; 16: 1012. 
6. Seibold JR, Harris JN, D'Angelo WA et al. Skin 
thickness and skin edema in systernic sclerosis. Arthritis 
Rheum 1986; 29(suppl. 1): S3. 
7. Perlish JS, Lemlich G, Fleischmajer R. Identification 
of collagen fibrils in scleroderma skin. J Invest 
Dermatol 1988; 90: 48-53. 
8. Jayson Ml. Systemic sclerosis: a microvascular 
disorder. R Soc Med 1983; 76: 635-42. 
9. Fleischmajer R, Perlish JS. Capillary alterations 
in scleroderma. J Am Acad Dermatol 1980; 2: 161-
70. 
10. Fleischmajer R, Perlish JS, Shaw KV, et al. Skin 
capillarity changes in early systemic scleroderma. 
Arch Dermatol 1976; 112: 1553-7. 
11. Tan EM: Antinuclear antibodies in scleroderma. 
Int J Dermatol 1981; 20: 569-73. 
12. White I, Needleman B. Immunologic aspects of 
scleroderma. Curr Opin Rheumatol 1992; 4: 826-8. 
13. McKee PH. Scleroderma and related conditions 
in pathology of the skin. Gower Medica! Publishing 
London, 1989, 1117-36. 
14. Thomas JR, Winklemann RK. Vascular ulcers in 
scleroderma. Arch Dermatol 1983; 119: 803-7. 
15. Bazen PG, Askari A. Localized scleroderma 
with cutaneous calcinosis. Arch Dermatol 1979; 115: 
871-2. 
16. Serup J. Clinical appearance of skin lesions and 
disturbances of pigmentation in localized scleroderma. 
Acta Derm Venereol 1984; 64: 485-92. 
acta dermatovenerologica A .P.A. Vol 4, 95, No 1 
17. Sanchez JL, Vasquez M, Sanchez NP. Vitiligo-
like macules in systemic scleroderma. Arch Dermatol 
1983; 119: 129-33. 
18. Fitzpatrick TB, Eisen AZ, Wolff K, Freedberg 
IM, Frank Austen K. Disorder of pigmentation. In 
"Dermatology in general medicine" (third edition) 
McGraw Hill, 1990; 1: pag. 836. 
19. Bettley FR, Seville RH. Nodular scleroderma. 
Proc 10th Int Cong Dermatol London, 1952; 479-81. 
20. Dortwart BB. Periorbital edema in progressive 
systemic scleroderma. Ann Int Med 1974; 80: 273. 
21. Ghersetich I, Teofoli P, Benchi M, Innocenti S, 
Lotti T. Localized Scleroderma. Scleroderma: from 
morphea to Systemic Sclerosis: Clinics in Dermatology. 
In: Elsevier ed. 1994; 12(2): 237-242. 
22. Huffstutter JE, DeLustro F A, LeRoy EC. Cellular 
immunity to collagen and laminin in scleroderma. 
Arthritis Rheum 1985; 28: 775-80. 
23. Ferrara J, Guillen FJ, Sleckman B et al. Cutaneous 
acute graft versus host disease to histocompatibility 
antigens in a murine model: histologic analyses and 
correlation to clinical disease. J Invest Dermatol 
1986; 86: 371-75. 
24. Fleischmajer R, Perlish JS, Reeves JR. Cellular 
infiltrates in scleroderma skin. Arthritis Rheum 1977; 
20: 975-84. 
25. Claman HN. On scleroderma mast cells, endothelial 
cells and fibroblasts. JAMA 1989; 262: 1206-9. 
26. Jablonska S, Chorzelski T, Maciejowska E. The 
scope and limitations of the immunofluorescence 
method in the diagnosis of lupus erythematosus. Br 
J Dermatol 1970; 83: 242-47. 
27. Mauch C, Krieg T. Fibroblast and matrix 
interactions and their role in the pathogenesis of 
fibrosis. Rheum Dis Ciin N Am 1990; 16: 93-107. 
28. Freedman RR, Ianni P. Role of cold and 
emotional stress in Raynaud's disease and scleroderma. 
Br J Dermatol 1983; 287: 1499-1502. 
29. Rustin MHA, Kovacs IB, Sowemimo-Coker SO 
et al. Differences in red cell behaviour with Raynaud's 
phenomenon and systemic sclerosis and patients 
with Raynaud disease. Br J Dermatol 1985; 113: 
265-72. . 
30. Harper FE, Marico HR, Turner RE, et al. A 
prospective study of Raynaud phenomenon and early 
17 
connective tissue disease. Am J Med 1982; 72: 883-8. 
31. Yune YH, Vix VA, Klatte EC. Early fingertip 
changes in scleroderma. J Am M Assoc 1971; 215: 
1113-6. 
32. Greaves M, Malia RG, Milford-Ward et al. 
Elevated von Willebrand factor antigen in systemic 
sclerosis; relationship to visceral disease. Br J 
Rheumatol 1988; 27: 281-5. 
33. Lotti T, Matucci-Cerinic M, Marmugi M, Fabbri 
P. Cutaneous fibrinolytic activity in scleroderma. 
Ciin Exp Rheum 1985; 3: 249-53. 
AUTHORS' ADDRESSES 
18 
Matteo L. Cagnoni, MD, Via Bolognese Vecchia 178, 50139 Firenze, Italy 
Torello Lotti MD, professor of dermatology, same address 
acta dennatovenerologica A.P.A. Vol 4, 95, No 1