The Journal of Dermatology Vo!. 19: 113-11R, 1992
Primary Systemic Amyloidosis: An Unique Case Complaining of Diffuse Eyelid Swelling and Conjunctival Involvement Shigeruko lijima Abstract A 52-year-old Japanese woman with the chief complaint of marked swelling of her upper eyelids and a mass over the bulbar conjunctiva is reported. She previously noticed frequent purpura after minimal trauma, which was resolved shortly after taking some ascorbic acid. Laboratory data showed Ig-G K type M-protein in the serum and K type Bence:Jones protein in the urine by immunoelectrophoresis. Systemic examination showed mild hepatosplenomegaly, 1st degree of AV block, and a mild increase in plasma cells in the bone marrow biopsy. Histologically, the whole dermis of the eyelid skin and conjunctiva was replaced by a large quantity of amorphous, eosinophilic substances, which were diffusely positive with Direct Fast Scarlet 4BS. Immunohistochemical staining was positive for anti-amyloid P component antibody. Typical amyloid fibrils were proved by electron microscopy. She was finally diagnosed as primary systemic amyloidosis with diffuse swollen eyelids and conjunctival mass, symptoms which in primary systemic amyloidosis are very rare.
Key words: primary systemic amyloidosis; diffuse eyelid swelling; conjunctival involvement; M-protein; Ig G-K type
Introduction Primary systemic amyloidosis frequently involves mesenchymal tissue rather than a parenchymal organ and is associated with cutaneous lesions in about 30% of the cases. Among cutaneous lesions, petechiae and ecchymoses are most common. These are seen mainly on the face, especially on the eyelids and in the periorbital region. In addition, discrete or confluent waxy yellow small papules or nodules on the eyelids are also fairly common and are said to be characteristic in diagnosing this disease. But swelling of the eyelids and/or conjunctival involvement are rarely seen in primary systemic amyloidosis. I herein report a Japanese woman who Received August 16, 1991; accepted for publication December 9,1991. Department of Dermatology, Mho Red-Cross Hospital, 3-12-48Sannomaru, Mito, Ibaraki 31D,Japan. Reprint requests to: Shigeruko Iijima, M.D.,Department of Dermatology, Mito Red-Cross Hospital, 3-12-48 Sannomaru, Mito, Ibaraki 31D,Japan.
complained of frequent purpura of the body, bilateral swelling of eyelids and swollen material of conjunctiva with extensive rich vascularity, and was finally diagnosed as primary systemic amyloidosis. Report of a Case A 52-year-oldJapanese woman visited the dermatology clinic at Mito Red Cross Hospital, Japan, in September of 1989, with the chief complaint of visual disturbance due to marked swelling of her left upper eyelid and a translucent mass over the left bulbar conjunctiva. There was no history of trachoma, vereneral conjunctivitis or any other chronic inflammation around the eyes. She first noticed frequent purpura on her skin, even after a minimal trauma, when she was about 47 years old. Since then, her left upper eyelid has been swollen. About a year later, some translucent material gradually appeared on the bulbar conjunctiva of the left eye. She had taken some ascorbic acid as a treatment for the purpura since she was 50 years old, and the frequency and degree of the purpura had resolved somewhat. However the swelling of the eyelid and
Primary Systemic Amyloidosis Involved Eyelids and Conjunctiva
IF;
a. The dermis was replaced by faintly eosinophilic bundles, like degenerative collagen materials. Small capillaries beneath the epithelium were dilated (bulbar conjunctiva, HE staining).
b. Most of the collagen bundles were unevenly stained with Direct Fast Scarlet 4BS (bulbar conjunctiva, amyloid staining).
A lot of extravasation was seen around the vein in the middle dermis. The walls were thickened by the same eosinophilic materials (eyelid skin, amyloid staining). c.
Fig. 3. Histological findings of the upper eyelid and conjunctiva.
116
Iijima
rial was stained diffusely but unevenly positive with Direct Fast Scarlet 4BS, which is the effective factor for Dylon amyloid staining, and showed birefringence and dichroism under polarized light. In the upper dermis, especially in the conjunctiva, a lot of capillaries were dilated in the irrregular form, and some of them showed red cells inside. At the middle to deep dermis in the eyelid skin, massive extravasation of red cells was present especially around the middle-sized veins. A moderate number of chronic inflammatory cells were present beneath the epithelium in the conjunctiva. A rectal biopsy was also done and showed perivascular positive amyloid staining. Immunohistochemically, those substances in the dermis were stained positive with anti-amyloid P antibody, and were partially positive with anti-x and anti-A. antibody. They were negative with anti-AA antibody. Electron microscopically, those masses were proved to be amyloid islands composed of straight, non-branching, 8-12 nm amyloid fibrils (Fig. 4). After the resection of the mass, the disease was still progressive. The conjunctival mass completely encircled the corneoscleral limbal and perilimbal area.
Discussion Primary systemic amyloidosis, induding "myeloma-associated amyloidosis", is a disease in which amyloids, originating from monoclonal immunoglobulin light chains (L chains) are deposited in the various tissues, especially muscles, skin and nerves. The deposition results in clinically significant symptoms. Macroglossia, digestive disorders, and polyneuropathy associated with amyloidosis are relatively common and may be related to amyloid infiltration of muscles of the tongue, intestinal muscles, and peripheral nerves, respectively. The reported incidence of mucocutaneous lesions in primary and myeloma-associated amyloidosis range from 29% (l) to 40% (2). Purpura is the most common manifestation, which is due to the infiltration of blood vessel walls by amyloid deposits. Generally, smooth, shiny, yellow- or skin-colored translucent waxy non-tender papules and plaques, often with a hemorrhagic component, are the most typical
Fig. 4. Electron microscopic findings of the upper eyelid. A vessel (V) was surrounded by amyloid islands (A). Fibroblasts were stretched among those islands. A red cell (R) was extravasated (up). Amyloid islands were composed of fine fibrillar materials, sized between 8 and 12 nm (bottom). and characteristic lesions and the eyelids are the most commonly involved sites in the body. However, diffuse swelling of the eyelids, as in our case, is not a common symptom in primary systemic amyloidosis (3). Furthermore, con-
Primal), Systemic Amyloidosis Involved Eyelids and Conjunctiva
117
Table 1. Reponed cases of primary localized coniunccvat amyloidosis (1980-) Patient Age Sex
Reponed year
Author
1983
Schaldenbrand JD 7 l
21
M
as
1984
Borodic CS)
30
F
aD
1986
Rosenblatt M9)
1986
Yokogawa
27 26 57
M M M
as aD as
HIO)
Location conjunctiva eyelid conjunctiva eyelid conjunctiva conjunctiva conjunctiva eyelid orbit
Complaint swelling of upper eyelid swelling of upper eyelid light colored plaque flat yellow plaque mass of upper eyelid
as: left eye, Ol): right eye junctival involvement, even hemorrhage in the conjunctiva, is also very rare in the systemic form ofthis disease (4). Only a few cases have been reported as showing conjunctival involvement due to amyloid deposition in primary nonfamilial systemic amyloidosis (5, 6). The two reported cases clinically showed normalappearing conjunctiva, and were only detected by special staining. On the other hand, primary localized amyloidosis is a disease in which amyloids of unknown origin deposit only at a limited site, such as the skin, larynx, tracheobronchial tree, heart, ureters, urinary bladder, urethra, or the eyes and their adnexae. Those localized aggregates of amyloid are not associated with systemic disease. Cases of primary localized conjunctival amyloidosis (PLCA) reported in the English and Japanese literature since 1980 are listed in Table 1 (7-10). As shown in Table 1, the symptoms of the conjunctiva and eyelids tend to appear coincidentally, so that a complaint of the eyelids sometimes reveals a lesion of the conjunctiva, and viceversa. Painless induration and tumefaction of the eyelid and/or conjunctiva constitute the most common complaint in primary localized conjunctival amyloidosis (3). The swelling of the eyelid sometimes looks like ptosis, due to the weight of the amyloid, but is rarely due to the isolated involvement of the levator palpebrae superioris muscle. The main symptoms around the eyes in our case were very similar to the one of PLCA.
However she had other systemic complaints and data. She formerly showed easy ecchymosis after minimal trauma. This is because the amyloid originated from monoclonal immunoglobulin light chains deposited in the walls of blood vessels. The fragility of the vessels was reduced by taking ascorbic acid, which is involved in the synthesis of intercellular substances, including the intercellular cement of the capillary endothelia. Moreover, she suffered from diarrhea, mild hepatosplenomegaly, and 1st degree of AV block. These probably involved amyloids on the digestive tract, liver, spleen, and heart. I examined the changes in the eyelids and conjunctiva by specific amyloid staining, polarized light, immunohistochemical staining and electron microscopy, and diagnosed primary systemic amyloidosis, possibly AL amyloidosis. We proved that these changes were caused by diffuse amyloid deposition, not only around the blood vessels but throughout the whole dermis, involving the replacement of collagen bundles. Primary amyloidosis involving conjunctiva and eyelids, either systemic or localized, is very rare, and all of them have been reported from ophthalmology. I have reported a Japanese woman with primary systemic amyloidosis complaining of PLCA symptoms. In the primary form of amyloidosis, the smooth waxy nontender papules and plaques with hemorrhaging are key symptoms for the diagnosis. I wish to emphasize that diffuse eyelid swelling,
118
Iijima
such as edema of the eyelids, is also a symptom. References I) Rubinow A, Cohen AS: Skin involvement in generalized amyloidosis, Ann Int Med, 88: 781-785, 1978. 2) Barth WF, Willerson JT, Waldmann TA, Decker JL: Primary amyloidosis. Clinical, immunochemical and immunoglobulin metabolism studies in fifteen patients, Am] Med, 47: 259-273, 1969. 3) Brownstein MH, Eliott R, Helvig E: Ophthalmologic aspects of amyloidosis, Am] Ophthalmol, 69: 423-430, 1970. 4) StansburyJR: Conjunctival amyloidosis in association with systemic amyloid disease, Am] Ophthalmol, 59: 24-29, 1965. 5) PurcelllJ Jr, Birkenkamp R, Tsai CC, Riner RN: Conjunctival involvement in primary systemic nonfamilial amyloidosis, Am] Ophthalmol, 95: 845-847, 1983. 6) Bene C, Kranias G: Ocular a myloidosis: Clinical
7)
8)
9)
10)
II)
points learned from one case, Ann Opahihalmol, 22: 101-102,1990. Schaldenbrand JD, Keren DF: Ig D amyloid in Ig D-rammda monoclonal conjunctival amyloidosis, Arch Pathol Lab Med, 107: 626-628, 1983. Borodic C, Beyer-Machule CK, Millin J, Conte J, Stephen-Foster C: Immunoglobulin deposition in localized conjunctival amyloidosis, Am] Ophthalmol, 98: 617-622, 1984. Rosenblatt M, Spitz GF, Friedman AH, Kazam ES: Localized conjunctival amyloidosis: Case reports and review of literature, Ophthalmologica, 192: 238-245, 1986. Yokogawa H, Inoue M, Ito H: Localized'amyloidosis of the eyelid, orbit and conjunctiva, Folia Ophthalmol lap, 37: 843-848,1986. Fett DR, Putterman AM: Primary localized amyloidosis presenting as an eyelid margin tumor, Arch Ophthalmol, 104: 584-585, 1986.
Primary Systemic Amyloidosis: An Unique Case Complaining of Diffuse Eyelid Swelling and Conjunctival Involvement Shigeruko lijima Abstract A 52-year-old Japanese woman with the chief complaint of marked swelling of her upper eyelids and a mass over the bulbar conjunctiva is reported. She previously noticed frequent purpura after minimal trauma, which was resolved shortly after taking some ascorbic acid. Laboratory data showed Ig-G K type M-protein in the serum and K type Bence:Jones protein in the urine by immunoelectrophoresis. Systemic examination showed mild hepatosplenomegaly, 1st degree of AV block, and a mild increase in plasma cells in the bone marrow biopsy. Histologically, the whole dermis of the eyelid skin and conjunctiva was replaced by a large quantity of amorphous, eosinophilic substances, which were diffusely positive with Direct Fast Scarlet 4BS. Immunohistochemical staining was positive for anti-amyloid P component antibody. Typical amyloid fibrils were proved by electron microscopy. She was finally diagnosed as primary systemic amyloidosis with diffuse swollen eyelids and conjunctival mass, symptoms which in primary systemic amyloidosis are very rare.
Key words: primary systemic amyloidosis; diffuse eyelid swelling; conjunctival involvement; M-protein; Ig G-K type
Introduction Primary systemic amyloidosis frequently involves mesenchymal tissue rather than a parenchymal organ and is associated with cutaneous lesions in about 30% of the cases. Among cutaneous lesions, petechiae and ecchymoses are most common. These are seen mainly on the face, especially on the eyelids and in the periorbital region. In addition, discrete or confluent waxy yellow small papules or nodules on the eyelids are also fairly common and are said to be characteristic in diagnosing this disease. But swelling of the eyelids and/or conjunctival involvement are rarely seen in primary systemic amyloidosis. I herein report a Japanese woman who Received August 16, 1991; accepted for publication December 9,1991. Department of Dermatology, Mho Red-Cross Hospital, 3-12-48Sannomaru, Mito, Ibaraki 31D,Japan. Reprint requests to: Shigeruko Iijima, M.D.,Department of Dermatology, Mito Red-Cross Hospital, 3-12-48 Sannomaru, Mito, Ibaraki 31D,Japan.
complained of frequent purpura of the body, bilateral swelling of eyelids and swollen material of conjunctiva with extensive rich vascularity, and was finally diagnosed as primary systemic amyloidosis. Report of a Case A 52-year-oldJapanese woman visited the dermatology clinic at Mito Red Cross Hospital, Japan, in September of 1989, with the chief complaint of visual disturbance due to marked swelling of her left upper eyelid and a translucent mass over the left bulbar conjunctiva. There was no history of trachoma, vereneral conjunctivitis or any other chronic inflammation around the eyes. She first noticed frequent purpura on her skin, even after a minimal trauma, when she was about 47 years old. Since then, her left upper eyelid has been swollen. About a year later, some translucent material gradually appeared on the bulbar conjunctiva of the left eye. She had taken some ascorbic acid as a treatment for the purpura since she was 50 years old, and the frequency and degree of the purpura had resolved somewhat. However the swelling of the eyelid and
Primary Systemic Amyloidosis Involved Eyelids and Conjunctiva
IF;
a. The dermis was replaced by faintly eosinophilic bundles, like degenerative collagen materials. Small capillaries beneath the epithelium were dilated (bulbar conjunctiva, HE staining).
b. Most of the collagen bundles were unevenly stained with Direct Fast Scarlet 4BS (bulbar conjunctiva, amyloid staining).
A lot of extravasation was seen around the vein in the middle dermis. The walls were thickened by the same eosinophilic materials (eyelid skin, amyloid staining). c.
Fig. 3. Histological findings of the upper eyelid and conjunctiva.
116
Iijima
rial was stained diffusely but unevenly positive with Direct Fast Scarlet 4BS, which is the effective factor for Dylon amyloid staining, and showed birefringence and dichroism under polarized light. In the upper dermis, especially in the conjunctiva, a lot of capillaries were dilated in the irrregular form, and some of them showed red cells inside. At the middle to deep dermis in the eyelid skin, massive extravasation of red cells was present especially around the middle-sized veins. A moderate number of chronic inflammatory cells were present beneath the epithelium in the conjunctiva. A rectal biopsy was also done and showed perivascular positive amyloid staining. Immunohistochemically, those substances in the dermis were stained positive with anti-amyloid P antibody, and were partially positive with anti-x and anti-A. antibody. They were negative with anti-AA antibody. Electron microscopically, those masses were proved to be amyloid islands composed of straight, non-branching, 8-12 nm amyloid fibrils (Fig. 4). After the resection of the mass, the disease was still progressive. The conjunctival mass completely encircled the corneoscleral limbal and perilimbal area.
Discussion Primary systemic amyloidosis, induding "myeloma-associated amyloidosis", is a disease in which amyloids, originating from monoclonal immunoglobulin light chains (L chains) are deposited in the various tissues, especially muscles, skin and nerves. The deposition results in clinically significant symptoms. Macroglossia, digestive disorders, and polyneuropathy associated with amyloidosis are relatively common and may be related to amyloid infiltration of muscles of the tongue, intestinal muscles, and peripheral nerves, respectively. The reported incidence of mucocutaneous lesions in primary and myeloma-associated amyloidosis range from 29% (l) to 40% (2). Purpura is the most common manifestation, which is due to the infiltration of blood vessel walls by amyloid deposits. Generally, smooth, shiny, yellow- or skin-colored translucent waxy non-tender papules and plaques, often with a hemorrhagic component, are the most typical
Fig. 4. Electron microscopic findings of the upper eyelid. A vessel (V) was surrounded by amyloid islands (A). Fibroblasts were stretched among those islands. A red cell (R) was extravasated (up). Amyloid islands were composed of fine fibrillar materials, sized between 8 and 12 nm (bottom). and characteristic lesions and the eyelids are the most commonly involved sites in the body. However, diffuse swelling of the eyelids, as in our case, is not a common symptom in primary systemic amyloidosis (3). Furthermore, con-
Primal), Systemic Amyloidosis Involved Eyelids and Conjunctiva
117
Table 1. Reponed cases of primary localized coniunccvat amyloidosis (1980-) Patient Age Sex
Reponed year
Author
1983
Schaldenbrand JD 7 l
21
M
as
1984
Borodic CS)
30
F
aD
1986
Rosenblatt M9)
1986
Yokogawa
27 26 57
M M M
as aD as
HIO)
Location conjunctiva eyelid conjunctiva eyelid conjunctiva conjunctiva conjunctiva eyelid orbit
Complaint swelling of upper eyelid swelling of upper eyelid light colored plaque flat yellow plaque mass of upper eyelid
as: left eye, Ol): right eye junctival involvement, even hemorrhage in the conjunctiva, is also very rare in the systemic form ofthis disease (4). Only a few cases have been reported as showing conjunctival involvement due to amyloid deposition in primary nonfamilial systemic amyloidosis (5, 6). The two reported cases clinically showed normalappearing conjunctiva, and were only detected by special staining. On the other hand, primary localized amyloidosis is a disease in which amyloids of unknown origin deposit only at a limited site, such as the skin, larynx, tracheobronchial tree, heart, ureters, urinary bladder, urethra, or the eyes and their adnexae. Those localized aggregates of amyloid are not associated with systemic disease. Cases of primary localized conjunctival amyloidosis (PLCA) reported in the English and Japanese literature since 1980 are listed in Table 1 (7-10). As shown in Table 1, the symptoms of the conjunctiva and eyelids tend to appear coincidentally, so that a complaint of the eyelids sometimes reveals a lesion of the conjunctiva, and viceversa. Painless induration and tumefaction of the eyelid and/or conjunctiva constitute the most common complaint in primary localized conjunctival amyloidosis (3). The swelling of the eyelid sometimes looks like ptosis, due to the weight of the amyloid, but is rarely due to the isolated involvement of the levator palpebrae superioris muscle. The main symptoms around the eyes in our case were very similar to the one of PLCA.
However she had other systemic complaints and data. She formerly showed easy ecchymosis after minimal trauma. This is because the amyloid originated from monoclonal immunoglobulin light chains deposited in the walls of blood vessels. The fragility of the vessels was reduced by taking ascorbic acid, which is involved in the synthesis of intercellular substances, including the intercellular cement of the capillary endothelia. Moreover, she suffered from diarrhea, mild hepatosplenomegaly, and 1st degree of AV block. These probably involved amyloids on the digestive tract, liver, spleen, and heart. I examined the changes in the eyelids and conjunctiva by specific amyloid staining, polarized light, immunohistochemical staining and electron microscopy, and diagnosed primary systemic amyloidosis, possibly AL amyloidosis. We proved that these changes were caused by diffuse amyloid deposition, not only around the blood vessels but throughout the whole dermis, involving the replacement of collagen bundles. Primary amyloidosis involving conjunctiva and eyelids, either systemic or localized, is very rare, and all of them have been reported from ophthalmology. I have reported a Japanese woman with primary systemic amyloidosis complaining of PLCA symptoms. In the primary form of amyloidosis, the smooth waxy nontender papules and plaques with hemorrhaging are key symptoms for the diagnosis. I wish to emphasize that diffuse eyelid swelling,
118
Iijima
such as edema of the eyelids, is also a symptom. References I) Rubinow A, Cohen AS: Skin involvement in generalized amyloidosis, Ann Int Med, 88: 781-785, 1978. 2) Barth WF, Willerson JT, Waldmann TA, Decker JL: Primary amyloidosis. Clinical, immunochemical and immunoglobulin metabolism studies in fifteen patients, Am] Med, 47: 259-273, 1969. 3) Brownstein MH, Eliott R, Helvig E: Ophthalmologic aspects of amyloidosis, Am] Ophthalmol, 69: 423-430, 1970. 4) StansburyJR: Conjunctival amyloidosis in association with systemic amyloid disease, Am] Ophthalmol, 59: 24-29, 1965. 5) PurcelllJ Jr, Birkenkamp R, Tsai CC, Riner RN: Conjunctival involvement in primary systemic nonfamilial amyloidosis, Am] Ophthalmol, 95: 845-847, 1983. 6) Bene C, Kranias G: Ocular a myloidosis: Clinical
7)
8)
9)
10)
II)
points learned from one case, Ann Opahihalmol, 22: 101-102,1990. Schaldenbrand JD, Keren DF: Ig D amyloid in Ig D-rammda monoclonal conjunctival amyloidosis, Arch Pathol Lab Med, 107: 626-628, 1983. Borodic C, Beyer-Machule CK, Millin J, Conte J, Stephen-Foster C: Immunoglobulin deposition in localized conjunctival amyloidosis, Am] Ophthalmol, 98: 617-622, 1984. Rosenblatt M, Spitz GF, Friedman AH, Kazam ES: Localized conjunctival amyloidosis: Case reports and review of literature, Ophthalmologica, 192: 238-245, 1986. Yokogawa H, Inoue M, Ito H: Localized'amyloidosis of the eyelid, orbit and conjunctiva, Folia Ophthalmol lap, 37: 843-848,1986. Fett DR, Putterman AM: Primary localized amyloidosis presenting as an eyelid margin tumor, Arch Ophthalmol, 104: 584-585, 1986.
