A Concise History of Ophthalmic Blastomycosis

A Concise History of Ophthalmic Blastomycosis Brett Pariseau, MD, MS,1 Mark J. Lucarelli, MD,2 Richard E. Appen, MD3

Blastomycosis History

History of Ophthalmic Infections

Blastomycosis was first described by Gilchrist1 at a meeting of the American Dermatological Association in Washington, DC, in 1894. Gilchrist initially thought the infection was protozoan, but in 1896 he concluded that it was a yeast.2 Early clinical investigation was performed at Cook County Hospital and Rush Medical College, and later at Duke University in the 1930s. By 1908, Montgomery and Ormsby3 compiled 22 cases in a literature review. Other cases soon followed, but because of poor reporting and citation, case duplication in multiple journals, and paper recycling,4 – 8 it is difficult to corroborate case reports or to find some references in the early literature. This confusion was further complicated in Europe by Otto Busse, who in 1894, 3 months after Gilchrist presented his findings, incorrectly identified Cryptococcosis neoformans as a blastomycete, which led to cases of cryptococcosis or torulosis being diagnosed as European blastomycosis.9,10 This ambiguous use of the term blastomycosis to describe any infection caused by yeastlike organisms was recognized in the 1930s by Martin and Smith, who wrote that of the 347 case reports of the time, “only 23 percent of these cases can be considered as unquestionably proved to be caused by Blastomyces dermatitidis.”11 They proposed that the term blastomycosis be reserved for disease caused only by B. dermatitidis, but confusion continued until at least the 1950s.12–14

Reports of ophthalmic infection are arranged by primary author, publication date, and PubMed Unique Identifier in Table 1. In 1904, Wood15 estimated that approximately 25% of systemic blastomycosis infections affect the eyelids based on his compilation of 9 cases, 6 previously published. This statistic propagated through the literature until 1995,16 –25 when Bartley26 reviewed the charts of 79 patients with blastomycosis treated at the Mayo Clinic and found that only 1 had infected eyelids. Mohney27 questioned this lower incidence in 1996. Churchill and Stober28 were the first to report intraocular infection in 1914, proven by cultures obtained via a vitreous puncture. By the early 1960s, it was recognized that the increasing incidence of ocular fungal infections was probably the result of “the widespread and indiscriminate use of corticosteroids in ocular therapy.”29 Perhaps the most interesting aspect of Table 14,15–19,22,23,24,26,28,30 –51 is how few infections were actually proven by ocular culture or biopsy during treatment, even in modern times.

Originally received: August 1, 2006. Final revision: May 5, 2007. Accepted: May 7, 2007. Available online: August 7, 2007. Manuscript no. 2006-857. 1 Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin. 2 Oculoplastics Service, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin. 3 Neuro-ophthalmology Service, Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, Wisconsin. Supported in part by an unrestricted grant to the University of Wisconsin Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness, Inc., New York, New York. The authors have no conflict of interest regarding any material presented in the article. Correspondence to Brett Pariseau, MD, MS, Department of Ophthalmology and Visual Sciences, University of Wisconsin Hospital and Clinics, 600 Highland Avenue, F4/336, Madison, WI 53792.bpariseau@ sbcglobal.net © 2007 by the American Academy of Ophthalmology Published by Elsevier Inc.

References 1. Gilchrist TC. Protozoan dermatitis. J Cutan Genitourin Dis 1894;12:496 –9. 2. Gilchrist TC. A case of blastomycetic dermatitis in man. Johns Hopkins Hosp Rep 1896;1:269 –90. 3. Montgomery FH, Ormsby OS. Systemic blastomycosis: its etiologic, pathologic and clinical features as established by a critical survey and summary of twenty-two cases, seven previously unpublished; the relation of blastomycosis to coccidioidal granuloma. Arch Intern Med 1908;2:1– 41. 4. Hyde JN, Ricketts HT. A report of two cases of blastomycosis of the skin in man, with a survey of the literature of human blastomycosis; with pathological report of the two cases. J Cutan Genitourin Dis 1901;19:44 –59. 5. Ricketts HT. Oidiomycosis (blastomycosis) of the skin and its fungi. J Med Res 1901:6;373–546. 6. Hyde JN, Montgomery FH. A brief summary of the clinical, pathologic and bacteriologic features of cutaneous blastomycosis (blastomycetic dermatitis, of Gilchrist), from the observations of Dr. James Nevins Hyde and the writer, with illustrations from thirteen cases, three of them hitherto unpublished. JAMA 1902;38:1486 –93. 7. Hektoen L. Systemic blastomycosis and coccidioidal granuloma. JAMA 1907;49:1071–7. 8. McKee SH. Blastomycosis of the eye. Arch Ophthalmol 1930; 3:301–5. 9. Busse O. Uber parasitare Zelleinschlusse und ihre Zuchtung. Zentralbl Bakteriol Mikrobiol 1894;16:175– 80. ISSN 0161-6420/07/$–see front matter doi:10.1016/j.ophtha.2007.05.048

e27

Ophthalmology Volume 114, Number 11, November 2007 10. Kaplan W, Clifford MK. Blastomycosis. I. A review of 198 collected cases in Veterans Administration hospitals. Am Rev Respir Dis 1964;89:659 –72. 11. Martin DS, Smith DT. Blastomycosis I. A review of the literature. Am Rev Tuberc 1939;39:275–304. 12. Pichette H. Clinical and histopathological consideration on a case of blastomycosis of the eye and face. Trans Can Ophthalmolog Soc 1949;12:111–23. 13. Theodorides E, Koutroklikos D. Blastomycosis of the conjunctiva. Am J Ophthalmol 1950;33:535– 8. 14. Theodorides E, Koutrokikos D. Blastomycosis of the conjunctiva: report of two additional cases. Am J Ophthalmol 1953;36:978 – 80. 15. Wood CA. Blastomycosis of the ocular structures, especially of the eyelids. Ann Ophthalmol 1904;13:92–103. 16. Jackson E. Blastomycosis of the eyelids with report of cases. JAMA 1915;65:23– 6. 17. Fagin R. A resume of the six cases of blastomycetic infection of eyelids reported in Memphis. Ophthalmoscope 1915;13: 426 –35. 18. McKee SH. Blastomycosis of the cornea, with a review of reported cases of blastomycosis of the eye. Int Clin 1926;3: 50 –7. 19. Schwartz VJ. Intra-ocular blastomycosis. Arch Ophthalmol 1931;5:581–90. 20. Birge HL. Ocular aspects of mycotic infection. AMA Arch Ophthalmol 1952;47:354 – 82. 21. Francois J, Rysselaere M. Oculomycoses. Springfield, IL: Thomas; 1972:188 –99. 22. Vida L, Moel SA. Systemic North American blastomycosis with orbital involvement. Am J Ophthalmol 1974;77: 240 –2. 23. Bond WI, Sanders CV, Joffe L, Franklin RM. Presumed blastomycosis endophthalmitis. Ann Ophthalmol 1982;14: 1183– 8. 24. Barr CC, Gamel JW. Blastomycosis of the eyelid. Arch Ophthalmol 1986;104:96 –7. 25. Brod RD, Clarkson JG, Flynn HW Jr, Green WR. Endogenous fungal endophthalmitis. In: Tasman W, Jaeger ED, eds. Duane’s Clinical Ophthalmology. Rev ed. Vol. 3. The Retina. Philadelphia: Lippincott; 1990:11.29 –39. 26. Bartley GB. Blastomycosis of the eyelid. Ophthalmology 1995;102:2020 –3. 27. Mohney BG. Blastomycosis of the eyelid [letter]. Ophthalmology 1996;103:544 –5. 28. Churchill T, Stober AM. A case of systemic blastomycosis. Arch Intern Med 1914;13:568 –74. 29. Suie T, Havener WH. Mycology of the eye: a review. Am J Ophthalmol 1963;56:63–77. 30. Li S, Perlman JI, Edward DP, Weiss R. Unilateral Blastomyces dermatitidis endophthalmitis and orbital cellulitis: a case report and literature review. Ophthalmology 1998;105: 1466 –70.

e28

31. Desai AP, Pandit AA, Gupte PD. Cutaneous blastomycosis: report of a case with diagnosis by fine needle aspiration cytology. Acta Cytol 1997;41(suppl):1317–9. 32. Chakravarty A, Salgia R, Mason E, et al. Pneumonia and infraorbital abscess in a 29-year-old diabetic pregnant woman. Chest 1995;107:1752– 4. 33. Gottlieb JL, McAllister IL, Guttman FA, Vine AK. Choroidal blastomycosis: a report of two cases. Retina 1995;15:248 –52. 34. Lopez R, Mason JO, Parker JS, Pappas PG. Intraocular blastomycosis: case report and review. Clin Infect Dis 1994;18: 805–7. 35. Mason JO III, Parker JS. Subconjunctival miconazole and anterior segment blastomycosis [letter]. Am J Ophthalmol 1993;116:506 –7. 36. Slack JW, Hyndiuk RA, Harris GJ, Simons KB. Blastomycosis of the eyelid and conjunctiva. Ophthal Plast Reconstr Surg 1992;8:143–9. 37. Safneck JR, Hogg GR, Napier LB. Endophthalmitis due to Blastomyces dermatitidis: case report and review of the literature. Ophthalmology 1990;97:212– 6. 38. Lewis H, Aaberg TM, Fary DR, Stevens TS. Latent disseminated blastomycosis with choroidal involvement. Arch Ophthalmol 1988;106:527–30. 39. Margo CE, Bombardier T. The diagnostic value of fungal autofluorescence. Surv Ophthalmol 1985;29:374 – 6. 40. Bongiorno FJ, Leavell UW, Wirtschafter JD. The black dot sign and North American cutaneous blastomycosis. Am J Ophthalmol 1974;78:145–7. 41. Rodrigues M, Laibson P. Exogenous mycotic keratitis caused by Blastomyces dermatitidis. Am J Ophthalmol 1973;75:782–9. 42. Lockwood WR, Allison F Jr, Batson BE, Busey JF. The treatment of North American blastomycosis: ten years’ experience. Am Rev Respir Dis 1969;100:314 –20. 43. Font RL, Spaulding AG, Green WR. Endogenous mycotic panophthalmitis caused by Blastomyces dermatitidis: report of a case and a review of the literature. Arch Ophthalmol 1967; 77:217–22. 44. Blodi FC, Huffman WC. Cicatricial ectropion caused by cutaneous blastomycosis. AMA Arch Ophthalmol 1958;59:459 – 62. 45. Sinskey RM, Anderson WB. Miliary blastomycosis with metastatic spread to posterior uvea of both eyes. AMA Arch Ophthalmol 1955;54:602– 4. 46. Cassady JV. Uveal blastomycosis. AMA Arch Ophthalmol 1946;35:84 –97. 47. Martin DS, Smith DT. Blastomycosis II. A report of thirteen new cases. Am Rev Tuberc 1939;39:488 –515. 48. Moore JT. Blastomycosis: report of a case dying from abscess of the brain. Surg Gynecol Obstet 1920;31:590 – 4. 49. Wilder WH. Blastomycosis of the eyelid. JAMA 1904;43: 2026 –30. 50. Coates WE. A case of blastomycetic dermatitis— clinically and histologically, an epithelioma. Medicine 1900;6:100 –12. 51. Gilchrist TC, Stokes WR. The presence of an oidium in the tissues of a case of pseudo-lupus vulgaris. Bull Johns Hopkins Hosp 1896;7:129 –39.

Pariseau et al 䡠 A Concise History of Ophthalmic Blastomycosis Table 1. Ophthalmic Blastomycosis Cases Author(s), Year, Reference [PubMed Unique Identifier]

Ophthalmic Infection

Pariseau et al, Left optic nerve 2007, and chiasm current study

Li et al, 199830 Right [9709759] endophthalmitis, whitish-yellow choroidal lesion, orbital abscess cellulitis Desai et al, 199731 [9990265]

Left 3⫻2-cm medial canthus/ lower lid lesion

Bartley, 199526 Right lower-lid [9098311] lesion

Chakravarty et Subcutaneous nodule that al, 199532 [7781379] became a right infraorbital abscess Gottlieb et al, 199533 [7569353]

Case 1: 7 large yellow choroidal lesions, 3⫹ vitreous flare right eye; case 2: bilateral multiple elevated choroidal lesions

Lopez et al, 199434 [8075276]

Left iris 4⫻4-mm mass, hazy cornea, cloudy lens, 5-mm domed-shaped choroidal mass

Extraocular Infection; Systemic Symptoms

Diagnostic Method or Specimen Source

Chest Radiograph Findings

Treatment

Lungs; no

H&E, GMS stains of 1⫻2-cm nodule in the Two dexamethasone left optic nerve, right upper lobe at tapers, three 80-mg autofluorescence, the level of the prednisone doses, lung needle biopsy fourth rib amphotericin B for 12 with cultures days, itraconazole 200 mg twice daily for 6 mos No; no H&E, GMS, PAS Patchy opacity in Cyclopentolate 1%, stains of right upper lobe prednisolone acetate enucleated eye 1% drops, oral and orbital prednisone 40 mg/day, abscess; BAL and isoniazid, rifampin, abscess cultures ethambutol, amphotericin B No; no H&E, GMS, Unknown Ketoconazole 400 mg/day mucicarmine for 30 days, stains of fineitraconazole 400 mg/ needle aspiration day for 6 mos cytologic sample Facial skin, Initial biopsy Unknown “Topical medications,” possible right interpreted as a incision and drainage knee joint; yes chalazion; second ⫻3, subtotal excision, biopsy showed itraconazole 200 mg fungus, H&E, bid for 5 wks, then GMS, PAS stains, 200 mg/day for a total culture of 6 mos Lung; yes No organisms in Right lower and Amphotericin 1.5 g needle aspiration middle lobe sample of abscess, infiltrates with but BAL and regional adenopathy abscess culture and possible pleural results positive effusion Case 1: skin Case 1: cheek, arm, Case 1: normal; case Case 1: oral ketoconazole lesions on abdomen, and 2: bilateral diffuse 500 mg bid, face, torso, back skin lesion miliary nodular amphotericin B 2 g; and limbs, biopsies; Case 2: infiltrates case 2: initially treated swollen joints, open lung biopsy, for tuberculosis, brain lesions; several skin lesion amphotericin B 2 g yes; Case 2: biopsies; lung, lungs, skin, and urine maculopapular culture results rash; yes positive, CSF culture results negative

Skin, Biopsy and cultures subcutaneous of a skin abscess nodules, lungs; in the lower yes abdominal wall; bronchial washings and transbronchial biopsies “nondiagnostic”

3-cm right lung perihilar opacity, small calcified lesion in left lung base

Steroid drops, betamethasone subconjunctival injections, systemic steroids, amphotericin B 1.26 g, 14 subconjunctival injections of miconazole 5 mg/0.5 ml, ketoconazole 400 mg/day for 6 mos, miconazole drops

Outcome Blind left eye, right eye 20/25 with a hemianopia

Enucleation, longterm outcome unknown

No yeast in fineneedle aspiration cytologic sample after 78 days Lesion healed, knee pain resolved in 5 wks

“Good response”

Case 1: complete resolution of brain and skin lesions and osteomyelitis, choroidal lesions resolved with scarring, chronic macular edema; case 2: inactive choroidal lesions, resolved skin lesions, residual lung scarring at 6 mos Vision stabilized to 20/80, cataract formation, choroidal lesion healed, residual lung scarring

(Continued)

e29

Ophthalmology Volume 114, Number 11, November 2007 Table 1. (Continued.) Author(s), Year, Reference [PubMed Unique Identifier]

Ophthalmic Infection

Extraocular Infection; Systemic Symptoms

Diagnostic Method or Specimen Source

Chest Radiograph Findings

Mason and Parker, 199335 [8213986]

Diffuse skin Right iris 4-mm lesions; yes mass, 5-mm choroidal mass This is the same case described by Lopez et al.34

Skin biopsy results “disclosed Blastomyces dermatitidis”

Slack et al, 199236 [1520658]

Recurring left upper lid lesion, 4 ulcerated nodular lesions on inferior bulbar conjunctiva, corneal erosion

No; no

Safneck et al, 199037 [2326009]

Right swollen lids, injected conjunctiva, edematous cornea, hypopyon, rubeosis, IOP: 45 mmHg Left choroidal yellow 3-mm raised lesion with medium internal reflectivity

No; yes

Initially identified as Diffuse interstitial a severely pattern inflamed squamous papilloma; KOH preparation, GMS, PAS stains of conjunctival biopsy; eyelid, conjunctival, and biopsy culture results positive None before “No significant enucleation; H&E, abnormalities” GMS stains of enucleated eye tissue

Lewis et al, 198838 [3355423]

Barr and Gamel, 198624 [3942552] Margo and Bombardier, 198539 [3992475] Bond et al, 198223 [6984622]

e30

Right calf skin lesion, lungs; yes

Left lower lid large Forehead, scalp, papillomatous forearm lesion lesions; no

Unknown

H&E, GMS stains of Left lung apical right calf skin infiltrate with lesion residual scarring at 6 mos

Treatment

Outcome

Corticosteroid drops, Iris mass resolved 8 amphotericin B 1.26 g, days after 14 injections of starting subconjunctival miconazole, miconazole 5 mg/0.5 choroidal mass ml, oral ketoconazole resolved after 4 for 6 mos mos, visual acuity 20/20 at 14 mos Excision, cryotherapy Visual acuity ⫻2, topical improved to 20/ erythromycin, 20 at 1 mo, lid sulfacetamide, contour grossly polymyxin B, normal at 5.5 neomycin, mos hydrocortisone, dexamethasone, oral ketoconazole 200 mg bid Topical antibiotics, local Enucleation and systemic steroids: after enucleation, amphotericin B 1.91 g

Treated for cough, low- Lesion nearly flat 2 grade fever with wks after a 12amoxicillin, day hospital stay, erythromycin, inactive at 6 mos amoxicillin/clavulanate potassium, 10 days each, amphotericin B 2g Full-thickness skin grafts No recurrence, from upper lids, topical other skin potassium iodide lesions remained solution, amphotericin nonprogressive B 410 mg Unknown; lesion initially Unknown identified as squamous cell carcinoma

Cultures taken from Unknown small dermal abscesses, H&E, GMS stains of specimen “Hyperkeratotic Unknown; Autofluorescing yeast Unknown eyelid lesion” unknown in an H&Estained biopsy sample Right eye: anterior Raised pustular KOH preparations of Sarcoid patient with Treated initially for Died after being chamber 3⫹ skin lesions left thigh skin bilateral hilar presumed sarcoidosis, readmitted for 4 cell, KP, large on face, scalp, biopsy, exudates adenopathy in oral prednisone tapers, mos pale-yellow hands, left from skin lesions, whom bilateral betamethasone 1 ml elevated arm, legs and neck mass, lower lobe infiltrates subconjunctival choroidal lesion. feet, prostate, prostatic fluid, developed injection, Left eye: mild neck mass, CSF; brain and amphotericin B 400 cell and flare, 3 brain, dura; dura biopsies mg, slightly whiter yes hydroxystilbamidine choroidal lesions isethionate 225 mg/ day, amphotericin B, intravenous miconazole (Continued)

Pariseau et al 䡠 A Concise History of Ophthalmic Blastomycosis Table 1. (Continued.) Author(s), Year, Reference [PubMed Unique Identifier] Bongiorno et al, 197440 [4835066]

Ophthalmic Infection Cicatricial ectropion all 4 eyelids, left dense vascularized leukoma

Extraocular Infection; Systemic Symptoms

Diagnostic Method or Specimen Source

Neck, face, KOH smears and eyelid, and cultures of skin forehead skin; lesions/scrapings unknown

Vida and Left exophthalmos, Lung, left Moel, 197422 orbital abscess temporal [4812094] mass; yes

Chest Radiograph Findings “Negative”

BronchoscopePleural effusion on obtained cytologic readmission material, cytologic analysis of orbital abscess

Treatment “Drops” without effect, amphotericin B 2 g over 8 wks, topical: mydriatics, 0.1% amphotericin B, neomycin, polymyxin, chloramphenicol First admission: amphotericin B 1.928 g; second admission: amphotericin B 2.5 g, 3 ml drained from abscess

Outcome Skin lesions cleared; full thickness skin grafts to all lids

No visual acuity loss, Hertel 17 mm in the right eye, 20 mm in the left eye 2 mos after abscess drainage Case 1: unknown; case 2: enucleation

Rodrigues and Laibson, 197341 [4574747]

Case 1: dense No; unknown. Case 1: corneal Case 1: normal; case irregular opaque No; unknown H&E, PAS, and 2: unknown cornea, central GMS slides leaking contained yeast descemetocele. and hyphae, Case 2: opaque confirmed by cornea, inflamed immunofluorescence; iris, and ciliary case 2: same, but body. from enucleated eye

Lockwood et al, 196942 [5820331]

Osseous hard palate lesion compressing the chiasm Panophthalmitis including optic nerve leptomeningeal sheath Cicatricial ectropion of all 4 lids

Unknown; unknown

Unknown

Unknown

No; no

H&E, GMS, PAS stains of enucleated eye

Diffuse interstitial pulmonary fibrosis and emphysema

Topical steroids, carbonic Enucleation, died a anhydrase inhibitors few weeks after hospital discharge

Skin lesions on entire face and neck; no

Skin lesion smears, cultures, and biopsy

Unknown

Intravenous stilbamidine isethionate 5.55 g

Full- and splitthickness skin grafts to lids

Both choroids, all 4 lids

Skin lesions on Skin lesion smears face, arms, trunk, eyelids, lungs; yes

Diffuse miliarylike infiltration throughout both lungs

Died

Cassady, 194646

Right iridocyclitis

Skin, lungs, Microscopic prostate, examination of kidneys, bone; eye tissue at yes autopsy

Initially treated as miliary tuberculosis, then with intravenous stilbamidine isethionate Unknown

Martin and Smith, 193947

Scarred and contracted eyelids, tortuous retinal vessels

Skin lesions on Skin lesion smears; face, right negative culture shoulder, arm, results ankle; yes

Irregular scattered areas of consolidation with linear bands extending outward from the hilus Generalized fibrosis Mechanical cleansing, and pleural chlorozone ointment, thickening over the oral potassium iodide, apices ethyl iodide inhalations, XRT

Font et al, 196743 [6019015] Blodi and Huffman, 195844 [13507786] Sinskey and Anderson, 195545 [13257992]

Case 1: “Various antibiotics, corticosteroids and patching,” 8.5-mm penetrating corneal transplantation; case 2: Neosporin, chloramphenicol, gentamicin, prednisone, and atropine drops, contact bandage, subconjunctival gentamicin Unknown Survived

Died

Died

(Continued)

e31

Ophthalmology Volume 114, Number 11, November 2007 Table 1. (Continued.) Author(s), Year, Reference [PubMed Unique Identifier] Schwartz, 193119

McKee, 192618 Moore, 192048

Jackson, 191516

Fagin, 191517

Churchill and Stober, 191428 Wilder, 190449

Wood, 190415

Hyde and Ricketts, 19014 Coates, 190050 Gilchrist and Stokes, 189651

Ophthalmic Infection

Extraocular Infection; Systemic Symptoms

Diagnostic Method or Specimen Source

Chest Radiograph Findings

Treatment

Outcome

Right thickened cornea, chemosis, posterior synechiae with an iris mass forming an abscess Left corneal ulcer, all 4 eyelids

Skin, Sputum, pus from leg Autopsy revealed Unknown; initially Died subcutaneous abscess, smear and miliary nodules mistaken for tissues, lungs, cultures from throughout both tuberculosis spleen, left anterior chamber lungs with left lung knee joint; yes pus, microscopic dense adhesions examination of eye tissue at autopsy Facial and neck Slides from corneal Unknown “Large doses of potassium Unknown skin; ulcer scrapings iodide” unknown Left orbital abscess, Left temporal Pus examination Unknown Curettage of skin Died left upper lid skin and abscesses, oral bone, brain potassium iodide, abscesses; yes XRT, 1% copper solution irrigation of orbit, enucleation Case 1: right lids, Case 1: facial Case 1: pus Case 1: unknown; case Case 1: curettage, boric Case 1: died; case left upper lid, and neck skin; examination; case 2: unknown acid, oral potassium 2: lesions healed opaque right no. Case 2: 2: smears from pus iodide, scar massage, cornea. Case 2: none; no silver nitrate; case 2: left lids excision, ulcer drainage, opening and scraping lids, silver nitrate, potassium iodide Six cases involving Facial skin, 1 Cultures, pus Unknown Some treated with Unknown, main eyelids with lesions examination, potassium iodide, case died on arms and tissue biopsy, some XRT, 1 with a skin suddenly legs; unknown cases not graft from arm documented Opaque right Skin, joints, Culture from Miliary blastomycotic Iron, quinine and Died cornea, irregular bones, lungs, vitreous humor, nodules, fibrosis and strychnine tonic, pupil, cloudy kidney, skin smears and abscesses found on potassium iodide, iris, congested prostate, cultures, autopsy autopsy copper sulfate conjunctivas spleen; yes findings Right eyelids, Facial skin; yes Agar cultures, smear Unknown XRT, potassium iodide, Corneal scarring conjunctivitis, of abscess ectropion treated with with 20/200 corneal ulcer, secretions grafts, pedicle flap visual acuity hypopyon Left lower lid Eyelid skin; no Skin biopsy Unknown Bathed with 1% salt Almost healed lesion; solution followed by summarizes 8 1% Ichthyol mixture prior eyelid cases in lanolin 4⫻/day, potassium iodide, XRT Left lower lid Nose, cheek and Tissue biopsy and Unknown Skin scrapings, oral Incomplete healing temple skin; cultures potassium iodide no Right lower lid Lip, finger, and Excisional biopsy Unknown Excision Unknown leg lesions; yes Eyelids “of both Face, right hand, Right eyebrow and Unknown Unknown Unknown eyes are scrotum, left right facial skin practically thigh, neck biopsies, cultures destroyed” skin; yes from pus

BAL ⫽ bronchioalveolar lavage; bid ⫽ twice daily; CSF ⫽ cerebrospinal fluid; GMS ⫽ Gomori methenamine silver; H&E ⫽ hematoxylin– eosin; IOP ⫽ intraocular pressure; KOH ⫽ potassium hydroxide; KP ⫽ keratoprecipitate; PAS ⫽ periodic acid–Schiff; XRT ⫽ radiation therapy.

e32