Fibrosis and fibrosing dermatitis
Philip E. LeBoit, M.D.
Depts. of Pathology and Dermatology
University of California, San Francisco
Fibrosing dermatitis refers to inflammatory conditions affecting the skin that result in
excess deposition of collagen. Along with these entities, we will consider the subject of
cutaneous fibrosis in general. While the deposition of collagen in fibrosing dermatitis is
driven by inflammatory cells, cytokines are also at work. These can evidently influence
fibroblasts to lay down collagen even without the proximity of inflammatory cells.
The various fibrosing dermatitides differ by virtue of the number of fibrocytes that are
present, the types of inflammatory cells and their distribution, and the quality of collagen
bundles that are laid down. Ackerman distinguishes between conditions that are
characterized by sclerosis and those that are not. He defines sclerosis as a diminished
number of fibroblasts, along with collagen fibers whose outlines are indistinct. An
example of this is lichen sclerosus et atrophicus. A diminished number of fibroblasts, but
maintenance of the outlines of collagen bundles occurs in morphea, scleroderma and some
related conditions. While this distinction is interesting, the word sclerosis is used mostly
by clinicians to denote any hardening of the skin, and the clinical definition and
histopathologic definition are easily confused.
Ackerman AB, Chongchitnant N, Sanchez J et al. Histologic Diagnosis of Inflammatory Skin Disease.
Williams & Wilkins, Baltimore, 1997 p. 95
Ulcers, granulation tissue, and dense inflammatory infiltrates of many kinds (esp.
neutrophils) can preceded fibrosis, in addition to the specific conditions we will
Scars are an under-explored area in dermatopathology. The recognition of scarring can be
critical in medicolegal matters, as the presence of a scar can be a clue to a previous
biopsy. Yet few pathology texts (or dermatopathology texts) give explicit criteria for
Scars- histopathologic findings
Diminished or absent adnexal structures
Horizontal orientation of fibrocytes and collagen bundles
Vertical or diagonal orientation of thin, straight vessels
Loss of the normal pattern of rete ridges and dermal papillae
Fibroblasts increased in number early, decreased late
Special kinds of scars include hypertrophic scars and keloids. Clinicians define a
hypertrophic scar as one that protrudes above the skin surface, and keloids as scars that
grow beyond their original bounds. Keloidal collagen bundles are thick, waxy, and often
fuse with one another. Not all keloid scars have keloidal collagen bundles, and some
hypertrophic scars do.
Hypertrophic scars- histopathologic findings
Features noted above, for ordinary scars
A nodular zone with markedly increased fibroblasts
Fibroblasts often have nuclei in lacunar spaces
Usually a zone of conventional scar is present between the nodular area and the
Keloid scars- histopathologic findings
Markedly protuberant, usually
Areas resembling hypertrophic scars, sometimes
Thick, waxy, and often fused collagen bundles
Large fibrocytes with vesicular nuclei
Keloidal collagen bundles can occur in the stroma of several neoplasms, including basal
cell and squamous cell carcinoma.
Fibrosis of the papillary dermis is a common finding due to inflammation or trauma
(sometimes iatrogenic, as in the case of liquid nitrogen treatment). The papillary dermis is
markedly expansible- it can be thickened upto 20 fold in some conditions. Common
examples of papillary dermal fibrosis that are not true inflammatory diseases in the sense
of being initiated by inflammatory cells include lymphedema, vascular stasis, the lamellar
and concentric fibroplasia of “dysplastic nevi”, regression of many neoplasms (melanoma,
mycosis fungoides, solar lentigo/lichenoid keratosis, superficial basal cell caricnoma, to
name the most common).
Fanti PA, Ragaz A, Ackerman AB. Expansibility of the papillary dermis. The position of the superficial
vascular plexus relative to the epidermis. Am J Dermatopathol. 1984 Jun;6(3):273-9
Dermatofibromas are considered as a form of fibrosing inflammation by some, and as
fibrosing neoplasms by others. There is certainly a resemblance between some examples
of dermatofibroma and granulation tissue, and other dermatofibromas and scars. Other
studies have shown clonality in dermatofibromas.
Anetoderma is a condition that presents with atrophy of the skin. There is often
maintenance of normal color and of the appearance of the surface, but palpation results in
a finger easily indenting the surface. Anetoderma was conceived of at one time as being
either “inflammatory” or “non-inflammatory”, but most studies support the concept that
inflammation is its antecedent in the vast majority of cases, the others being due to
Anetoderma- histopathologic features
Nearly normal appearance at scanning magnification
Inflammatory cells scant- some giant cells may be present
Slightly increased numbers of fibrocytes, sometimes
Diminished elastic tissue fibers in the mid-dermis on special stains
Preserved elastic tissue around vessels, adnexa
Venencie PY, Winkelmann RK.
Histopathologic findings in anetoderma.
Arch Dermatol. 1984 Aug;120(8):1040-4.
Venencie PY, Winkelmann RK, Moore BA.
Anetoderma. Clinical findings, associations, and long-term follow-up evaluations.
Arch Dermatol. 1984 Aug;120(8):1032-9.
Inflammatory diseases with fibrosis, principally of the papillary dermis
Inflammatory diseases resulting in fibrosis of the papillary dermis include lichen sclerosus
et atrophicus, radiation sclerosis and acrodermatitis chronica atrophicans.
Lichen sclerosus et atrophicus is a condition that usually affects anogenital skin, but also
occurs at other sites. Its lesions are usually hypopigmented (cream colored rather than
ivory). Genital lesions are often intensely pruritic, while extragenital ones are not. Genital
lichen sclerosus et atrophicus is associated with squamous cell carcinoma, while
extragenital diseaese is not. The reasons for this are unknown.
Lichen sclerosus et atrophicus, early changes
Bandlike infiltrates of lymphocytes
Psoriasiform epidermal hyperplasia
Many lymphocytes in the basal layer of the epidermis (resembling mycosis fungoides)
Distinctive changes in the papillary dermis (see below)may only be evident in levels
Fung MA, LeBoit PE.
Light microscopic criteria for the diagnosis of early vulvar lichen sclerosus: a
comparison with lichen planus.
Am J Surg Pathol. 1998 Apr;22(4):473-8.
Lichen sclerosus et atrophicus, fully developed changes
Thickening of the papillary dermis
Diminished fibroblasts in the papillary dermis
Pallor and homogenization of the papillary dermis
Variable degrees of lichen simplex chronicus
Acrodermatitis chronica atropihicans is a late complication of Lyme disease in which
striking atrophy occurs on acral skin. It is a more frequent complication in Europe, with
very few cases in North America. There are bandlike infiltrates with plasma cells early, an
atrophic epidermis, and fibrosis of the papillary dermis.
Inflammatory diseases with fibrosis principally of the reticular dermis
By far the most important spectrum of disease in which the reticular dermis is the seat of
fibrosing inflammation is that of morphea and scleroderma. The dividing line between
these conditions is not razor sharp, but they are distinct. The changes of morphea are
confined to the skin, and usually to discrete areas of the skin, while scleroderma is a
systemic disease (progressive systemic sclerosis) with many internal manifestations. Both
conditions begin with inflammatory cells, although they may be scant in scleroderma.
Some patients with morphea have superficial changes that are indistinguishable from those
of lichen sclerosus et atrophicus. This has led to the hypothesis that they are two
expressions of the same disease. An intersting sidelight is the occurrence of morphea on
the trunk and limbs, and lichen sclerosus et atrophicus on the genitalia of some European
patients infected with B. burgdorferi.
Morphea- histopathologic findings in early cases
Superficial and deep, perivascular and interstitial infiltrates of lymphocytes and plasma
cells (eosinophils or neutrophils, sometimes)
Some lymphocytes in the basal layer (may resemble mycosis fungdoides)
Thickening of collagen bundles may be subtle
Morphea- histopathologic findings in fully developed lesions
Inflammatory infiltrates less dense than in above
Thickened collagen bundles in the reticular dermis
Diminished spaces between them
Hyperpigmentation of the basal layer
Homogenization (but not usually pallor) of the papillary dermis
Morphea- histopathologic findings in late lesions
As in above
Adnexa often absent or show degenerative changes
The histopathologic findings in scleroderma are usually identical to those in late morphea.
Variants with different histopathologic findings -
The late stages of necrobiosis lipoidica can simulate morphea. Necrobiosis lipoidica is a
grnaulomatous dermatitis that results in fibrosis. Early lesions show palisaded
granulomatous infiltrates affecting the entire width of most biopsy specimens, with fibrosis
and degeneration of collagen bundles in the centers of the granulomatous foci. There are
infiltrates of lymphocytes and plasma cells. In late lesions, the granulomatous changes can
be subtle, and fibrosis marked. Both conditions can have plasma cells. A clue to the
diagnosis of necrobiosis lipoidica is that an elastic tissue stain will show near absence of
elastic fibers, while those are mostly preserved in morphea.
Several epidemics due to toxic substances resulted in hardening of skin simulating scleroderma or morphea,
and recently, scleromyxedema.
Spanish olive oil-epidemic syndrome
L-tryptophan (eosinophilia/myalgia syndrome)
Nephrogenic fibrosing dermopathy
The first two conditions resemble scleroderma/morphea under the microscope:
Thickened collagen bundles throughout reticular dermis
Diminished spaces between thick collagen bundles
Superficial and deep perivascular and interstitial lymphocytic infiltrates, plasma cells around deep plexus
Mucin deposits sometimes greater than in conventional morphea
In Spanish toxic olive oil epidermic syndrome, some cases have increased fibroblasts or myofibroblasts
Nephrogenic fibosing dermopathy/nephrogenic systemic fibrosis occurs in patients with renal disease who
have been exposed to Gadolinium via radiologic procedures, MRI and MRA. The Gadolium particles
accumulate in lesional skin. Histopathologically, it can resemble scleromyxedema but clinically it is quite
Increased fibroblasts (esp. myofibroblasts) throughout dermis and subcutaneous septa
Small osteoclast like giant cells in cellular lesions
Increased interstitial mucin
Dystrophic calcification, sometimes
It differs from idiopathic scleromyxedema in that:
There is no paraprotein in serum
Face is usually spared
Waxy papules do not occur
No internal/psychiatric disease
No infiltrates of plasma cells
Mucin does not accumulate in “lakes”
Cowper SE, Su LD, Bhawan J, Robin HS, LeBoit PE. Nephrogenic fibrosing dermopathy.
Am J Dermatopathol. 2001 Oct;23(5):383-93.
Cowper SE, Robin HS, Steinberg SM, Su LD, Gupta S. LeBoit PE. Scleromyedema-like cutaneous
diseases in renal-dialysis patients. The Lancet. 356:1000-01, 2000.
Porphyria cutanea tarda can also result in fibrosing dermatitis. The lesions are usually in
sun exposed skin. A distinctive finding is the presence of thick walled blood vessels
whose walls can be stained with PAS-D.
Radiation sclerosis is a late complication of radiation exposure. The changes in the
reticular dermis resemble those of morphea, but fibroblasts can be large, or even have
bizarre nuclei (so-called radiation fibroblasts). Radiation fibroblasts fail to stain with
factor XIIIa or CD34, making them unlikely precursors of atypical fibroxanthoma or of
dermatofibrosarcoma protuberans. The findings in the papillary dermis can resemble those
of lichen sclerosus et atrophicus. Blood vessels can have fibrin deposits in their walls or
lumens, or can be necrotic. Changes that resemble morphea rather than radiation sclerosis
can occur following radiation for breast carcinoma.
Meehan SA, LeBoit PE.
An immunohistochemical analysis of radiation fibroblasts.
J Cutan Pathol. 1997 May;24(5):309-13.
Chronic fibrosing vasculitis
There are two forms of leukocytoclastic vasculitis that result in fibrosis, erythema
elevatum diutinum and granuloma faciale.
In erythema elevatum diutinum (EED), there are hemorrhagic papules that evolve into
plaques and nodules on the dorsal surfaces of joints. The distribution is bilateral, and
strikingly symmetrical in many cases. EED is associated with streptococcal infection, HIV
disease and hematologic disorders of several kinds.
In granuloma faciale (GF) there is usually a solitary plaque on the face. Sometimes
extrafacial lesions occur as well- but these are usually solitary, and if multiple, are not
distributed in the distinctive manner seen in erythema elevatum diutinum.
Erythema elevatum diutinum-early lesions
leukocytoclastic vasculitis involving small vessels in the dermis
An increase in small vessels, sometimes
Erythema elevatum diutinum-fully developed lesions
Dense, diffuse infiltrates of neutrophils and neutrophilic debris
Residual foci of vasculitis, sometimes
Thin collagen fibers increased
Erythema elevatum diutinum-late lesions
Parallel, thin collagen bundles
Neutrophils and dust between bundles
Vasculitic foci rare
In granuloma faciale, early lesions are almost never biopsied, as they are solitary lesions on
Granuloma faciale-fully developed lesions
Neutrophils and dust around small vessels
Fibrin in vessel walls
Eosinophils and plasma cells
Sparing of perifollicular adventitial dermis, often
Granuloma faciale-late lesions
Features noted above
Concentric fibrosis around vessels
Changes similar to those in either condition can sometimes occur as random, single
Carlson JA, LeBoit PE.
Related Articles, Links
Localized chronic fibrosing vasculitis of the skin: an inflammatory reaction that occurs
other than erythema elevatum diutinum and granuloma faciale.
Am J Surg Pathol. 1997 Jun;21(6):698-705.
LeBoit PE, Cockerell CJ.
Nodular lesions of erythema elevatum diutinum in patients infected with the human
J Am Acad Dermatol. 1993 Jun;28(6):919-22.
LeBoit PE, Yen TS, Wintroub B.
The evolution of lesions in erythema elevatum diutinum.
Am J Dermatopathol. 1986 Oct;8(5):392-402.
Fibrosing conditions of the subcutis
The subcutaneous septa can be thickened in several panniculitdes. In erythema nodosum,
fibrous septa are inflamed and thickened, but revert to normal thickness with healing. In
morphea profunda and in eosinophilic fasciitis (see above), there are usually changes in the
reticular dermis as well; sometimes those in the subcutis dominate the picture. In
necrobiosis lipoidica, a biopsy that extends into the subcutis will demonstrate marked
thickening of the septa.
Sclerosing panniculitis (lipodermatosclerosis) is a condition in which the subcutis is
altered by ischemia secondary to venous stasis. It results in woody, indurated plaques,
Sclerosing panniculitis- histopathologic findings
Changes of venous stasis in the papillary dermis
Thickening and fibrosis of septa
Ischemic necrosis of the centers of lobules
Lipomembranous change in lobules (corrugated membranous structures)
Jorizzo JL, White WL, Zanolli MD, Greer KE, Solomon AR, Jetton RL.
Sclerosing panniculitis. A clinicopathologic assessment.
Arch Dermatol. 1991 Apr;127(4):554-8.