Disorders9 SECTIONTissue Connective •
cyte count should be followed closely during therapy (initially every other day and weekly during maintenance therapy) and should not decrease below 3000 cells/mm3. Granulocyte count below 1500 cells/mm3 increases the risk of infection. Dosages must be decreased at the first sign of bone marrow suppression because the full effect of the present dose will not manifest in the white blood cell count until 1 week later. Hemorrhagic cystitis can be minimized by adequate hydration to prevent concentrated urine. Fortunately, hair regrows in most patients who experience hair loss while taking cyclophosphamide.
Complications of systemic corticosteroids include fluid retention, weight gain, moon face, hyperglycemia, osteoporosis, bone fractures, psychologic disturbances, peptic ulcers and infections. Side effects can be minimized by switching to treatment every other day and discontinuing steroids as soon as inflammation has been controlled.
FIGURE 100.1. Wegener granulomatosis-corneal thinning.
●Glomerulonephritis.
●Otitis media.
●Orbital pseudotumor.
●Other small-vessel vasculitis (Churg–Strauss syndrome, microscopic polyangiitis, Henoch–Schönlein purpura, and essential cryoglobulinemic vasculitis).
TREATMENT
Systemic
●Cyclophosphamide 2 mg/kg PO qd and continuing for 1 year after active disease has subsided.
●Prednisone 1 mg/kg PO qd for 4 weeks, followed by a tapered dose and discontinuation.
Ocular
●Topical eye lubricants (e.g. carboxymethylcellulose sodium 0.5%) every 30 minutes to 4 hours.
●Topical ophthalmic antibiotic solution or ointment (e.g. trimethoprim sulfate and polymyxin B sulfate) every 3 to 4 hours.
●Topical ophthalmic corticosteroid drops (e.g. prednisolone 1%) every 3 to 4 hours; cycloplegic eyedrops (e.g. tropicamide 1%) every 4 hours.
COMMENTS
Ophthalmologists’ awareness of Wegener granulomatosis will lead to prompt referral to internists and early treatment with cytotoxic and immunosuppressant drugs. The promptness of diagnosis and successful treatment may not only save lives but also preserve useful vision. Affected patients will have to be followed by internists and ophthalmologists to monitor treatment effectiveness and the side effects of cytotoxic and immunosuppressive drugs. Depending on disease activity, follow-up examinations daily or at intervals of several months are appropriate.
REFERENCES
Harper SL, Letko E, Samson CM, et al: Wegener’s granulomatosis: the relationship between ocular and systemic disease. J Rheumatol 28:1025–1032, 2001.
Hoffman GS, Kerr GS, Leavitt RY, et al: Wegener’s granulomatosis: an analysis of 158 patients. Ann Int Med 116:488–498, 1992.
Jayne D, Rasmussen N, Andrassy K, et al: A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med 349:36–44, 2003.
Kinyoun JL, Kalina RE, Klein ML: Choroidal involvement in systemic necrotizing vasculitis. Arch Ophthalmol 105:939–942, 1987.
Seo P, Stone JH: The antineutrophil cytoplasmic antibody-associated vasculitides. Am J Med 117:39–50, 2004
Surgical
●Orbital decompression in patients with optic nerve compression that is unresponsive to medical treatment.
●Grafts (e.g. severe corneal ulceration).
Other
●Methotrexate or azathioprine (may be useful for patients in remission who have serious side effects due to cyclophosphamide).
COMPLICATIONS
Disease-related complications include vision loss, renal insufficiency, subglottic stenosis, and decreased hearing. Permanent morbidity occurs in a majority of patients.
Complications of treatment with cyclophosphamide include bone marrow suppression, hemorrhagic cystitis, azoospermia, bladder carcinoma, nausea, vomiting and hair loss. The leuko-
101 WEILL–MARCHESANI SYNDROME
759.8
(Marchesani Syndrome, Spherophakia–
Brachymorphia Syndrome)
Teresa C. Chen, MD
Boston, Massachusetts
David Sellers Walton, MD
Boston, Massachusetts
ETIOLOGY/INCIDENCE
The Weill–Marchesani syndrome (WMS) is a very rare hereditary disorder that is manifested by microspherophakia, sublux-
184
ated lenses, high myopia, glaucoma, short stature, joint stiffness, and brachydactyly. It demonstrates both autosomal recessive and autosomal dominant transmission.
COURSE/PROGNOSIS
●Adult dwarfism.
●Occasional heart defects.
●Glaucoma, the most serious ocular complication.
DIAGNOSIS
Clinical signs and symptoms
Diagnosis is made by recognizing ocular and systemic abnormalities. The affected lenses are small in diameter, are thickened, and often become dislocated anteriorly or inferiorly. Following shallowing of the anterior chamber, glaucoma may occur secondary to the pupillary block mechanism and appositional crowding of the angle due to a forward position of the lens iris diaphragm. The small stature of patients with this disorder can be striking and is associated with marked extremity abnormalities.
Laboratory findings
Delayed carpal ossification is revealed by radiography.
Differential diagnosis
●Other causes of dwarfism.
●Mucopolysaccharidoses.
●Isolated hereditary lens subluxation and myopia.
●Hereditary microspherophakia.
PROPHYLAXIS
Laser iridotomy may be performed in cases in which there is threatened pupillary block and associated angle closure.
TREATMENT
Ocular
●Optical correction for myopia and astigmatism.
●Glaucoma treatment: When glaucoma is present, topical β- blockers, alpha adrenergics, carbonic anhydrase inhibitors, and prostaglandin agents may be helpful.
●Pupillary block glaucoma: In the absence of lens subluxation, miotics may induce or exacerbate pupillary block. Cycloplegics/mydriatics may relieve pupillary block but may also increase the risk of spontaneous lens dislocation into the anterior chamber.
Surgical
Patients at risk for pupillary block glaucoma should be followed regularly with gonioscopy. Iridotomy is indicated to prevent and relieve pupillary block. Following iridotomy, laser iridoplasty may be helpful to further open the angle.
Goniosynechialysis may be necessary to remove an iris that is adherent to the trabecular meshwork so as to restore trabecular function. Early operation following angle closure is desirable.
Other surgeries that may ultimately be needed for the treatment of glaucoma may include the following: pars plana lensectomy, anterior vitrectomy, sutured posterior chamber intraocular lens (PCIOL) placement and/or tube shunt surgery. Phacoemulsification with in-the-bag (modified or unmodified) capsular tension ring and PCIOL has also been performed.
COMPLICATIONS
●Blindness secondary to glaucoma.
●Dwarfism.
●Clumsiness secondary to hand deformities.
COMMENTS
Genetic counseling is indicated. There is evidence of clinical homogeneity despite genetic heterogeneity in autosomal recessive (AR) and autosomal dominant (AD) families. These results underscore the difficulties for genetic counseling in supposed sporadic cases.
Loci have been mapped in AR WMS (19p13.3-p13.2) and AD WMS (15q21.1).
Systemic and ophthalmic screening should be performed to detect any previously unappreciated defects.
REFERENCES
Cionni RJ, Osher RH, Marques DM, et al: Modified capsular tension ring for patients with congenital loss of zonular support. J Cataract Refract Surg 29:1668–1673, 2003.
Faivre L, Dollfus H, Lyonnet S, et al: Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am J Med Genet 123A:204–207, 2003.
Harasymowycz P, Wilson R: Surgical treatment of advanced chronic angle closure glaucoma in Weill-Marchesani syndrome. J Pediatr Ophthalmol Strabismus 41:295–299, 2004.
Jensen AD, Cross HE, Paton D: Ocular complications in the Weill-Marche- sani syndrome. Am J Ophthalmol 77:261–269, 1974.
Ritch R, Wand M: Treatment of the Weill-Marchesani syndrome. Ann Ophthalmol 13:665–667, 1981.
Syndrome101 CHAPTERMarchesani–Weill •
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