Familial Progressive Scleroderma

Disorder characterized by progressive systemic sclerosis (scleroderma), calcium deposits (calcinosis) usually in the fingers, Raynaud syndrome, loss of muscle control of the esophagus (difficult swallowing), osseous deformity of the fingers (sclerodactyly), and small red spots (telangiectasia) on the skin (fingers, face) or inside the mouth.

Calcinosis.

5:10,000,000 in adults; only 3% of total cases affect children.

Unknown, but female-to-male ratio is 3:1. Dominant form described.

Collagen (types I and III), fibronectin, and proteoglycans are deposited in the interstitium and the intima of small arteries. Fibrosis (involving several cytokines, especially interleukin-4) is found in clinically affected and unaffected tissue. Calcinosis is caused by deposits of carbonated apatite B. Autoimmune mechanism is suspected (increased chromosomal breakage rate is predominantly observed in linkage disequilibrium with HLA haplotype A1, Cw7, B8, C4AQ0B1, DR3, which is frequently observed in autoimmune diseases). A linkage between the fibrillin-1 gene locus and the scleroderma phenotype is suspected. Because of the similarity of scleroderma to chronic graft-versus-host disease, microchimerism is suspected in the pathogenesis of the disorder.

Multisystemic disorder of connective tissue affecting the skin, which becomes hardened. Visceral involvement may be severe and affects the heart (myocardial fibrosis and secondary conduction defects, pericardial effusions), lung, kidneys (renal failure), intestinal tract (gastroesophageal reflux and strictures), and synovium. Whitish creamy discharge from the fingertips is observed occasionally. The deposit consists of carbonated apatite type B. The mineral substance seems to be less reactive and more stable than normal calcium pyrophosphate deposit in bone, explaining the total lack of effectiveness of calcium chelating agents.

Because of the numerous combinations of potential signs of the disorder, many clinical aspects are observed. Calcinosis (subcutaneous calcareous concretions), telangiectasia, and scleroderma (systemic sclerosis) are constant. Raynaud syndrome is very common. Scleroderma often results in esophageal motility disorders (with permanent strictures occasionally) and sclerodactyly. Calcinosis can involve many joints (elbows, shoulders), periarticular areas (flank), and viscera (heart). Clinically, the disorder is divided into two groups: (1) “pure” CREST (calcinosis cutis, Raynaud phenomenon, esophageal motility disorder, sclerodactyly, and telangiectasia), which occurs when patients have two or more symptoms of CREST but do not meet the criteria for either limited or diffuse scleroderma (no tight skin above their wrists, no pitting digital ulcers, no lung fibrosis; and (2) “plus CREST,” when CREST symptoms appear with another form of scleroderma (e.g., limited scleroderma plus CREST, diffuse scleroderma plus CREST, any other autoimmune disease plus CREST).

These patients are often treated with a systemic corticosteroid therapy; consequently, salt and water balance must be evaluated. Patients taking acetylsalicylic acid must be evaluated for bleeding. Evaluate mouth opening because of contracted perioral skin. Fiberoptic tracheal intubation should be available for induction of anesthesia. Pulmonary function tests prior to major procedures. Evaluation of cardiac, hepatic, and renal function is needed. Evaluation of venous access because of possible difficulties as a result of affected skin. Administration of antacid and cimetidine as premedication.

Regional anesthesia, particularly peripheral nerves blocks, must be used as often as possible. Depending on the type of surgery, regional anesthesia has proved to be very successful in adults and can be safely proposed in children. If general anesthesia is chosen, difficult tracheal intubation should be anticipated because of the association of limited mouth opening. The use of a rapid-sequence intubation technique because of gastric reflux must be evaluated in light of the mouth opening limitation. Inhalational induction using sevoflurane associated with cricoid pressure (even under fiberscope) seems to be the safest technique. Tracheal extubation should be performed only when the patient is completely awake and displays fully competent laryngeal reflexes.

Only depends on the multisystemic involvement and medication taken. Intraoperative corticosteroid supplementation must be considered.

Hereditary Telangiectasia: Autosomal dominant mucocutaneous and visceral fibrovascular dysplasia in which telangiectasia, arteriovenous malformations, and aneurysms may be widely distributed throughout the cardiovascular system. It is usually recognized as a “triad” of telangiectasia, recurrent epistaxis, and a family history of the disorder.

Morphea (Morphoea; Localized Scleroderma): Localized form of scleroderma characterized by thickening and induration of the skin and subcutaneous tissue as a consequence of excessive collagen deposition. Morphea subtypes are classified according to clinical presentation and depth of tissue involvement. They include plaque-like, generalized, linear, and deep varieties. Morphea lacks features such as sclerodactyly, Raynaud phenomenon, and internal organ involvement. Because of overproduction of collagen by lesional fibroblast, probably as a result of endothelial cell injury, inflammation and immunologic responses occur. The incidence rate is estimated to be 27 new cases per one million general population per year.

Scleroderma en Coup de Sabre (Proliferative Retinopathy): Bilateral linear scleroderma en coup de sabre is associated with facial hemiatrophy and neurologic dysfunctions. Affects usually one side of the face and head in the frontoparietal area with band-like indurated skin lesions. “En coup de sabre” is defined by a localized patch of scleroderma in the frontal region of the scalp, causing a cicatricial alopecia (resembles the scar of a wound made by a sabre).

Parry-Romberg Syndrome: Rare disorder characterized by progressive atrophy of one side of the face occasionally extending to other parts of the body. The process may, however, be bilateral in 5 to 10% of cases. Tissues involved include the skin, tongue (difficult intubation), gingiva, soft palate, nose, subcutaneous fat, larynx, muscle, and bone.

CREST Syndrome: One of the three divisions of scleroderma, which are morphea, linear scleroderma, and CREST syndrome.