Ophthalmic Surgery, Lasers and Imaging Retina

CASE REPORTS 

Corneal Melting and Scleromalacia Perforans in a Patient With Pyoderma Gangrenosum and Acute Myeloid Leukemia

Ramesh S Ayyala, FRCS, FRCOphth; Stewart Armstrong, FRCS, FRCOphth

Abstract

Abstract. Postoperative endophthalmitis may present in an atypical fashion (absent or minimal anterior chamber reaction) in the presence of underlying immunosuppressive disorder. The authors describe an apparently healthy 58-year-old man who displayed endophthalmitis with minimal anterior chamber reaction following penetrating keratoplasty for granular corneal dystrophy with underlying acute myeloid leukemia. Scleromalacia perforans in association with pyoderma gangrenosum subsequently developed, leading to ciliary staphyloma and corneal melting. Pyoderma gangrenosum is an uncommon, idiopathic skin disease that may also have ocular manifestations. [Ophthalmic Surg Lasers 1998;29:328-331.]

Abstract

Abstract. Postoperative endophthalmitis may present in an atypical fashion (absent or minimal anterior chamber reaction) in the presence of underlying immunosuppressive disorder. The authors describe an apparently healthy 58-year-old man who displayed endophthalmitis with minimal anterior chamber reaction following penetrating keratoplasty for granular corneal dystrophy with underlying acute myeloid leukemia. Scleromalacia perforans in association with pyoderma gangrenosum subsequently developed, leading to ciliary staphyloma and corneal melting. Pyoderma gangrenosum is an uncommon, idiopathic skin disease that may also have ocular manifestations. [Ophthalmic Surg Lasers 1998;29:328-331.]

Pyoderma gangrenosum is a destructive, necrotizing noninfective ulceration of the skin that presents as a furuncle-like nodule, pustule, or hemorrhagic bulla. ' Even though the exact mechanism remains unclear, it is felt to be a Shwartzmann-type reaction.2 However, there are many examples of depressed or abnormal immunologic responses in patients with pyoderma gangrenosum to support a belief that it is related to a defective immune system.3

T-cell subgroup abnormalities have been demonstrated in some patients with pyoderma gangrenosum, along with reduced production of macrophage inhibitory factor and disorder of Chemotaxis and phagocytosis by polymorphs and monocytes. The skin lesions have a classic clinical appearance, although there are no characteristic histopathologic changes or diagnostic laboratory tests for the disease. The lesions often start at the site of minor trauma or a surgical wound as a small erythematous papule. These progress to tender sterile pustules, the centers of which necrose with ragged undermined violaceous edges. According to Brusting et al.,4 the lesion consists of extensive undermining and necrosis of the subcutaneous tissue. The epidermis remains as a thin, gray-translucent film extending over the crater of the lesion in a ragged, irregular fashion, with a well-defined blue edematous and boggy border. The diagnosis, after the exclusion of other diseases, is essentially clinical. A biopsy is of value to exclude other disorders. Histopathology5 usually shows the features of a large sterile abscess formation in which venous and capillary thrombosis, hemorrhage, necrosis, and massive cell infiltration are present. The advancing border shows features of a lymphocytic vasculitis, suggesting the endothelial cell to be an early target.

Pyoderma gangrenosum is usually associated with debilitation by some infection or inflammatory process elsewhere in the body.6 Most commonly, it is associated with ulcerative colitis, Crohn's disease, rheumatoid arthritis, or other forms of polyarthritis. Rarely, it may be associated with diseases of the reticuloendothelial system, such as hypogammaglobulinemia and monoclonal gammopathies. Plasma cell dysctasia and frank myeloma have been recorded. The bullous hemorrhagic form is associated with myeloproliferative disease, such as acute myeloid leukemia. Systemically, the condition responds to steroids or sulfones. Ophthalmic manifestation of the disease is rare and of the seven reported cases only one presented as scleromalacia perforans.

CASE REPORT

An apparently healthy 58-year-old man was admitted for an elective full-thickness corneal graft to his left eye. His corrected visual acuity before surgery was 20/80 due to granular corneal dystrophy. Two days after the operation, the patient complained of severe throbbing pain behind the left eye. On the third day, he had lid swelling with a quiet eye and a clear graft. On the fourth postoperative day, a small starshaped exudate was noticed at the host graft interface. The anterior chamber showed a mild flare with no evidence of hypopyon.

A complete blood count revealed 6% blast cells (9% myelocytes and 4% promyelocytes) and a suspicion of incipient acute myeloid leukemia. This was later confirmed by a bone marrow biopsy. In view of the underlying immunosuppression, a possible diagnosis of endophthalmitis was entertained. An anterior chamber tap revealed Staphylococcus aureus and scanty polymorphs. Treatment was started with topical fortified vancomycin drops (10 mg/ml) every hour alternating with fortified gentamicin drops (15 mg/ml), and intravenous gentamicin (3 mg/kg/d administered in 3 equal doses every 8 hours). However, 3 days later, intravenous gentamicin was changed to netilmicin because of worsening anterior chamber and vitreous infiltrates. Netilmicin was administered intravenously in a dose of 6 mg/kg daily, but treatment was stopped after 7 days because of renal impairment.

Twenty-eight days after surgery, the visual acuity was hand motions close to the face, with no pain, edematous host cornea, a clear graft, and a small fibrin exudate in the anterior chamber. Treatment was continued with topical antibiotics and steroids. Thirty days later, the acute myeloid leukemia was treated with the DAT 3+10 induction protocol (i.e., daunorubicin 50 mg/ml 1-3 days, cytarabine 100 mg/ml 1-10 days and, thioguanine 100 mg/ml 1-10 days), which produced complete resolution. Recovery from chemotherapy was complicated by Staphylococcus albus septicemia from a Hickman line infection.

Three weeks later (50 days after the operation) extensive bullous necrotic lesions of the skin developed affecting mainly the trunk, lower limbs, and face. These lesions began as tender macules and progressed rapidly to large nodular purpuric areas with a narrow inflamed border and minimal discharge (Fig. 1). A diagnosis of pyoderma gangrenosum was made based on the clinical appearance. Biopsy of the skin lesion revealed venous and capillary thrombosis with intense lymphocytic infiltrate in the periphery and polymorphs in the center and was felt to be consistent with pyoderma gangrenosum. A rapid resolution was observed after treatment with 30 mg of prednisone daily.

Figure 1. The atrophic scar of pyoderma gangrenosum on the forearm of the patient.

Figure 1. The atrophic scar of pyoderma gangrenosum on the forearm of the patient.

One week after the skin eruptions, an area of scleral thinning was noticed approximately 3 mm above the limbus between the 1 1 -o'clock and 12-o'clock positions in an otherwise quiet eye. An anterior staphyloma developed and the host cornea began to melt at the superior and inferior graft- host interface. The patient remained in remission, but the anterior segment of the eye was badly damaged with an anterior staphyloma, an ectatic but clear graft, and ring anterior Synechie, plugging the graft-host interface. There was a mature cataract and perception of light in all quadrants.

Fourteen weeks after surgery, the host cornea perforated and the graft became unstable. The extensive destruction of the host cornea was deemed irretrievable and a potential source of infection during subsequent consolidative treatment of leukemia. The eye was enucleated.

Figure 2. Histology of the limbus revealing advanced stromal melting of the host sclerocornea (hematoxylin-eosin, original magnification ×15). s = sclera; i = site of iris impaction; he = thinned out host cornea; > = graft-host interface.

Figure 2. Histology of the limbus revealing advanced stromal melting of the host sclerocornea (hematoxylin-eosin, original magnification ×15). s = sclera; i = site of iris impaction; he = thinned out host cornea; > = graft-host interface.

Figure 3. Magnified view of the site of iris impaction with host corneal stromal thinning and evidence of inflammatory cellular infiltrate, (hematoxylin-eosin, original magnification ×65). i = site of iris impaction.

Figure 3. Magnified view of the site of iris impaction with host corneal stromal thinning and evidence of inflammatory cellular infiltrate, (hematoxylin-eosin, original magnification ×65). i = site of iris impaction.

HISTOPATHOLOGIC EXAMINATION

Macroscopic examination of the left eye showed an opaque cornea from which the corneal graft protruded, having been partly avulsed. Temporal vertical sectioning showed an opaque, cataractous lens and a pale cupped disc. Microscopic examination confirmed an anterior limbal staphyloma and pardy dehisced corneal graft, with iris incarceration, fracture of Descemets membrane, growth of a pupillary membrane, and angle closure. The stroma of the host cornea was extremely thin, with evidence of inflammatory cell infiltration (Figs. 2 and 3). There were collections of what looked like erstwhile bacterial colonies within the cornea, but these failed to stain with Gram-Twort stain or periodic acid-Schiff. There was no evidence of graft versus host disease. The absence of abscess formation and persistence of a plasma cell infiltrate was felt to be secondary to resolving infection. The appearance was felt to suggest postinfective staphyloma and corneal limbal melt. However, the possibility of pyoderma gangrenosum could not be entirely dismissed.

DISCUSSION

The present case is interesting, not only for its unusual association, but also for its illustration of some clinical variations (i.e., endophthalmitis in patients with suppressed or abnormal immune systems may present as an apparently quiet, but painful eye). A hypopyon may be absent. Bialasiewicz et al.7 described six patients with postoperative endophthalmitis after elective intraocular surgery suffering from immunosuppressive disorders ranging from chronic lymphatic leukemia, to agranulocytosis, to metastasizing antrum carcinoma and immunosuppressive therapy. Two of these patients required enucleation and a third patient lost light perception, leading the authors to conclude that extra precautions such as preoperative, perioperative, and intensive postoperative bactericidal antibiotics may be indicated in immunocompromised patients undergoing ocular surgery. If possible, ocular operations must be postponed in immunocompromised patients. Unfortunately, in the present case, the diagnosis of acute myeloid leukemia was made after the penetrating keratoplasty.

Pyoderma gangrenosum may be associated with scleromalacia perforans and corneal melting. Although leukemia and its treatment may be associated with ocular complications, the fact that the sclerocorneal melt was noticed a few days after the diagnosis of pyoderma gangrenosum in the present case probably implies that there is an association between the two. The process may be some form of abnormal immune mechanism leading to corneoscleral melting, similar to the condition seen in rheumatoid arthritis. This is supported by the fact that some cases of pyoderma gangrenosum with ocular involvement responded to immunosuppressive agents such as cyclophosphamide8 and azathioprine.9 We can find only one reference to an association between corneoscleral melting and pyoderma gangrenosum.8 Peyman et al. describes a patient who had severe sclerokeratitis with marginal corneal and scleral melting, progressing to perforation that responded to overlay corneoscleral patch grafting. The second eye of the same patient was involved with sclerokeratitis with melting at a later date and responded to cyclophosphamide. Scleromalacia perforans is a slow, painless form of necrotizing vasculitis.8 It typically occurs in women older than 50 years of age who have had rheumatoid arthritis for more than 15 years. It is also reported to occur in porphyria and Wegener's granulomatosis. Chemotherapeutic agents such as cyclophosphamide have been used to treat the condition. In more advanced cases, scleral grafts are advocated.

Lid ulcer, scleritis, and corneal perforation have been reported in association with pyoderma gangrenosum.9-13 Browning et al.11 reported a case of pyoderma gangrenosum involving the upper lid that resolved with a Chlorhexidine gluconate dressing during a 2-month period. Newman et al.12 recently reported a case of pyoderma gangrenosum involving the lower lid that resulted in destruction of the orbital contents with subsequent perforation of the globe and evisceration. This patient was subsequendy treated with hyperbaric oxygen with cessation of the disease process. Two cases of scleritis have been reported, one of which responded to oral corticosteroids13 and the other to a combination of oral corticosteroids and azathioprine.9 A case of bilateral corneal perforations in association with pyoderma gangrenosum was reported11; however, details regarding this patient are not available.

In conclusion, we recommend that elective intraocular surgery be postponed in the presence of abnormalities in the peripheral blood or in the presence of other indications of immunosuppression, and that consideration be given to the possible association of scleromalacia perforans in patients with a history of pyoderma gangrenosum. Immunosuppressive therapy may be considered in cases of pyoderma gangrenosum with ocular involvement not responding to conventional therapy.

REFERENCES

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2. Rostenberg A. The Shwartzmann phenomenon. Br J Dermatol. 1953;65:389-405.

3. Check IJ, Ellington EP, Moreland A, et al. T helper-suppressor cell imbalance in pyoderma gangrenosum, with relapsing polychondritis and corneal keratolysis. Am J Clin Pathol. 1983;80:396-399.

4. Brusting LA, Goeckerman WH, O'Leary PA. Pyoderma gangrenosum: clinical and experimental obsessions in five cases occurring in adults. Arch Dermatol. 1930;22:655-680.

5. Su WD, Schroeter AL, Perry HO, et al. Histopathologic and immunologic study of pyoderma gangrenosum. J Catan Pathol. 1986;13:323-330.

6. Callen JP. Pyoderma gangrenosum and related disorders. Adv Dermatol. 1989;4:51-70.

7. Bialasiewicz AA, WiIk CM, Ruprecht KW. Postoperative infections in systemic immunocompromising diseases: a study of six patients. Klin Monatsbl Augenheilkd. 1991;198:190-194.

8. Peyman GA, Sanders DR, Goldberg MF. Principles and Practice of Ophthalmology, vol. 1. Philadelphia: WB. Saunders; 1987:458.

9. Happle R, Schiffer H-P, Kovary PM. Ocular involvement in pyoderma gangrenosum. Arch Dermatol. 1977;1 13:1612.

10. Magid ML, Gold MH. Treatment of recalcitrant pyoderma gangrenosum with cyclosporine. / Am Acad Dermatol. 1989;20:293-294.

11. Browning DJ, Proja AD, Sanfilippo FP. Pyoderma gangrenosum involving the eyelid. Arch Ophthalmol. 1985;103:551-552.

12. Newman WD, Frank HJ. Pyoderma gangrenosum of the orbit. Eye. 1993;7:89-94.

13. Goettmann S, Guillame JC, Binaghi M, et al. Pyoderma gangrenosum superficial avec histologie psuedo-tuberculoide et atteinte oculaire. Ann Dermatol Venereol. 1989;116:831-832.

10.3928/1542-8877-19980401-13

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