An unusual dental phenomenon in systemic scleroderma

Review of the literature and report of two cases

 
Systemic scleroderma is a disease of unknown etiology characterized by excessive deposition of collagen and other connective tissue components in the skin and several internal organs. The most common oral findings are rigidity and thinness of lips, circumoral fibrosis which causes microstomia and inability to open the mouth widely. Involvement of tongue may lead to its decreased mobility and diminished size. Radiographic findings that have been classically associated with systemic scleroderma are widening of the periodontal ligament spaces and destruction of lamina dura, usually in posterior teeth. Intraoral radiographs of presented cases revealed apical resorption of the roots and destruction of the lamina dura verified on extraction of the teeth. This oral finding appears not to have been recorded by previous investigators of scleroderma.

 
Systemic scleroderma is a progressive chronic dis­ ease of unknown etiology characterized by excessive deposition of collagen and other connective tissue components in the skin and several internal organs, especially blood vessels, musculoskeletal system, gastro-intestinal tract, lungs, heart, and kidneys: It is associated with prominent and often severe alteration in the microvascular bed.1 Vascular changes consist of a paucity of blood vessels, thickening and hyalini-zation of their walls, and narrowing of the lumen.2
Although the disease may occur at almost any time in life, it is relatively uncommon in childhood, the onset being between 30 and 50 years of age.3
Most commonly, skin changes precede visceral involvement by several years.3 Cutaneous involve­ ment usually starts peripherally on the hands and face, and gradually extends centripetally.4 As a result of dif­fuse fibrosis of the subcutaneous fat, it becomes firmly bound to the underlying structures. Recurrent painful ulcerations are a common problem.3 The skeletal musculature is invariably affected, resulting in weak­ess and atrophy.4
Tissue culture and enzymatic studies have indi­ cated an increase in the activity of fibroblasts and in the production of collagen during the active stage of scleroderma.4 Electron microscopic observa­ tions have also indicated that the fibrous trabeculae of the subcutaneous tissue increased in thickness due to deposition of immature collagen fibrils, with a much smaller diameter than normal suggesting increased collagen synthesis in the subcutaneous tissue.3 These randomly arranged immature colla­ gen fibrils, range in diameter from 100Å to 400Å in contrast to the mature collagen fibers with a diame­ ter of approximately 700Å to 800Å.
The presence of immature collagen fibrils in the deep dermis from sclerodermatous skin and the elevated levels of the enzyme protocollagen proline hydroxylase, which correlate with the rate of new collagen synthesis, suggest that the excessive dermal collagen deposition is due to increased syn­ thesis.5 The stimulus for the excessive collagen deposition is unknown.5
Two factors are recognized in the etiology of scleroderma; it is both a vascular disease and an autoimmune disorder.4 It has been suggested that immunologic abnormalities play a role and that they are common denominator to rheumatoid arthritis, systemic lupus erythematosus, and dermatomyositis.3 Also, there is clinical overlap of scleroderma with those other presumed autoimmune disorders.5
In favor of an autoimmune etiology is the presence of anti-nuclear antibodies in the sera of about two-thirds of patients with systemic scleroderma. The titers of antibodies are frequently as high as in systemic lupus erythematosus.4 Rheumatoid factor also occurs in one-third of sclerodermal cases.5 Circulating immune complexes have been noted in scleroderma! patients with visceral involvement.5 Cellular infiltrates (predominantly T- lymphocytes) are found at the advancing edge of active scleroderma.5
In some cases of systemic scleroderma, epidermal nuclear IgG deposition is seen even in clinically nor­ mal skin as a result of high serum concentrations of antibody to nuclear antigen.4
Examination by direct immunofluorescence of kid­ ney biopsies of patients with renal involvement shows diffuse vascular depositions of immunoglobulins, pre­ dominantly IgM, and/or complement in the intima of the inter-lobular and arcuate arteries, which micro­ scopically often exhibit fibromucinous oblitera­ tions.4
In addition, hyperglobulinemia, usually moderate, with a diffuse non-specific increase in gamma globulin is present in about half of cases.5 Rheumatoid factor and anti-nuclear antibodies, usually showing a speck­ led or nucleolar pattern, have been demonstrated in a high percentage of patients.3
Lymphokines from phytohemagglutinin-stimulated normal human peripheral blood mononuclear cells can cause increased collagen synthesis by human embryonic lung fibroblasts.3 In addition, phytohemagglutinin-stimulated normal human lym­ phocytes have been reported to increase collagen production in cultures of human skin fibroblasts.3 Extracts of both normal and sclerodermatous skin can cause the release of macrophage- migration inhibiting factor by lymphocytes from patients with scleroderma but not from normal subjects.6 Whether collagen serves as an anti-antigen in the pathogenesis of scleroderma remains to be determined.3
Vascular abnormalities have been implicated in the pathogenesis of scleroderma based on the frequent occurrence of Raynaud's phenomenon, which usu­ ally precedes skin changes, or the presence of peri­ ungual telangiectases, and on the histologic and ultrastructural capillary abnormalities in the skin, mus­ cles, and other viscera.3
Electron microscopic examination has shown sig­ nificant changes in the small dermal blood vessels dur­ ing the early stages of the disease when light micro­ scopy shows no vascular changes.4 The main altera­ tions are vacuolization and ultimate destruction of endothelial ceils, reduplication of the basement mem­ brane, a perivascular infiltrate of mononuclear cells and the presence of fibroblasts and pericytes with enlarged rough endoplasmic reticulum, which is indi­ cative of increased activity and is accompanied by perivascular fibrosis.2 Perivascular cellular infiltrates and endothelial cell damage appear to precede the stage of fibrosis.2
Regarding the intraoral manifestations of the sys­ temic scleroderma, the tongue, soft palate, and the gingiva are the structures usually involved.7 Early mild edema of these structures are gradually fol­ lowed by atrophy and induration of mucosal and muscular tissues.7
The most common paraoral findings are rigidity and thinness of lips, circumoral fibrosis which causes puckering and pallor of the circumoral area when an attempt is made to gape the mouth
widely.1 Collagenization may proceed to produce microstomia.1 Inability to open the mouth may hin­ der mastication, speech, placement of prosthesis, and good oral hygiene.1 Involvement of the peri-temporomandibular joint tissues causes reduction of the opening of mouth and makes dental care very difficult.7
Extreme widening of the periodontal ligament, two to four times normal thickness, has been reported by Staphne and Austin as a characteristic of scleroderma.7 This may be so striking that, once the association is recognized, the occurrence of the periodontal disturbance as found on routine dental roentgenograms may be sufficient to establish a tenta­ tive diagnosis of scleroderma or acrosclerosis.7 Wide­ ning of periodontal ligament appears to be more com­ mon in acrosclerosis, and is probably related to the changes in the blood vessels of the periodontal liga­ ment.7
This finding, however, appears to be highly vari­ able. In one report, thickening of the periodontal ligament is noted in only 7% of 127 cases, whereas another found it in 37% of the 35 patients studied. The former study also noted a decrease in the width of the lamina dura of the affected teeth.
Additional radiographic changes reported include resorption of the angle of the mandible, the condyle, and the coronoid process. These osseous changes are apparently related to pressure atrophy or ischemia.1
Histologic features of the gingiva reveal thicken­ ing and hyaiinization of the collagen fibers, atrophy of the gingiva with loss of rete pegs and sclerosis of the walls of the blood vessels.7 The microscopic changes in the periodontal ligament consist of a widening as well as an appearance of hyaiinization with diminution in the number of connective tissue cells usually found.7

Case 1:

A 36-year-old female presented to the dental clinic with painful decayed teeth for which she wanted extractions. Physical examination of the patient revealed circumoral fibrosis which led to puckering around the mouth. The lips had become thin and the nose had the characteristic pinched appearance. The skin of the forehead was smooth and shiny (Fig. 1).
Flexion deformity of the inter-phalangeal joints was observed. The skin over hands was taut and parchment-like in consistency. The fingers showed tapering ends and crippling deformity {Fig. 2).
Intraoral examination, which was extremely dif­ ficult due to microstomia, revealed thin pale mucosal tissue, numerous missing teeth and decayed teeth. The gingival tissue showed indura­ tion and firmness.
Periapical intraoral radiographs, which were dif­ ficult to take, showed an inclined resorption in the apical part of the roots and complete destruction of the lamina dura. This was verified on extraction of the teeth, which showed clear root resorption in a fashion that looks like the silkworm-eaten appear­ ance (Figs. 3,4,5).

Case 2:

A 42-year-old male was admitted to the medical ward. Physical examination of the patient showed the external features of systemic scleroderma. He had a smooth shiny forehead, limitation in opening the mouth, and the hands showed stretched skin with finger deformity. Also, there was an ulcer on the dorsum ofthe right hand {Figs. 6 & 7).
Intraoral examination revealed normal mouth; the mucosal and gingival tissues were normal and carious cavities were detected. Periapical intraoral radiographs revealed apical root resorption and destruction of the lamina dura in some areas (Figs. 8 &9).

Root resorption in systemic scleroderma appears not to have been reported by previous investigators of scleroderma.
This unusual observed phenomenon, i.e., resorption of the teeth root apices, can be accounted for by: (1) decrease of the oxygen ten­ sion in the environment; (2) the immunologic reac­ tions which may take place in the course of the dis­ ease.
In 1970 Norton and Narco suggested that the vascular tissue is the primary target organ in scleroderma. They demonstrated a marked reduc­ tion in the number of capillaries with histologically abnormal structure in the skeletal muscles from scleroderma! patients.5
The vascular lesions involving the small arteries (150-500 um in diameter) are characterized by inti-mal proliferation and endothelial cell swelling, thinning of the media, and the presence of a peri-adventitial connective tissue cuff. Smaller arteries and arterioles may undergo intimal sclerosis, fib­ rinoid changes culminating in necrosis.8
There is a "bone cell lineage" of cells; the stem cell ofthis lineage is the osteoprogenitor cell, which can be differentiated along three sublines to form osteoblasts, osteoclasts, or chondroblasts. During the growth process, the fate of osteogenic cells, whether osteoblasts or osteoclasts, seems to depend on the oxygen content (low or high) of the environment in which they differentiate.9 The more oxygen tension allowed, the more osteoblasts will be produced.
In light of the above-mentioned data, we can say that decrease of the oxygen as a result of microves-sels obstruction will lead to increased osteoclastic activity. The microvessels around the root apices are those vessels which are suffering from obliteration.
Two elements may be suggested as the cause of root and bone resorption which are elaborated through immunological reactions. The first is the lymphokine named Osteoclast Activating Factor (OAF). The second is the protaglandins, which are liberated under the effect of complement system.10
Systemic scleroderma is characterized by the presence of anti- nuclear antibodies and these are produced in the presence of endogenous antigens, such as nucleic acid antigen as in lupus erythematosus. Circulating immune complexes have been noted in scleroderma! patients. Persistent liberation of antigen leads to increased depos­ ition of immune complexes. These immune com­ plexes in the tissues will activate the complement system. Activated complement system may enhance the synthesis of prostaglandins by bone locally. Prostaglandins, which are synthesized locally, exerts its biological effects at or near the site of synthesis. The mechanism by which the comple­ ment activation increase prostaglandin synthesis is not known.10
Prostaglandins have been detected in inflammed gingival tissue and exudates, as well as in the super-nants of rheumatoid synovial cultures.10
The rapidity and extent of bone resorption pro­ duced by prostaglandins suggest that a local syn­ thesis of lesser amounts over a long period of time could account for the bone loss in localized bone wasting disease.11 Fatty acids may also stimulate bone resorption directly.10
As the cellular infiltrates (predominantly T-lym-phocytes) are found in active scleroderma, these lymphocytes undergo blast transformation in response to antigens of the tissues and produce the lymphokine known as (OAF), which induces the osteoclasts to resorb the bone.12
In summary, the suggested sequence of events is as follows:

which stimulates osteoclasts to cause bone resorption and root resorption.
This account agrees with the previously reported data that bone changes are correlated with ischemia.