Orbit, 2014; 33(1): 62–64 ! Informa Healthcare USA, Inc. ISSN: 0167-6830 print / 1744-5108 online DOI: 10.3109/01676830.2013.842255
C ASE REPORT
Ocular Sarcoidosis and Immune Thrombocytopenia: A Rare Association John J. Chen1 and Richard C. Allen1,2 Department of Ophthalmology and Visual Sciences and 2Department of Otolaryngology – Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
ABSTRACT There is an association between sarcoidosis and immune thrombocytopenia, which can be severe and even fatal if left untreated. Although ocular sarcoidosis is one of the most common extrapulmonary manifestations of sarcoidosis, immune thrombocytopenia has not been reported in isolated ocular sarcoidosis. We present a patient with a remote history of immune thrombocytopenic purpura who developed a sub-conjunctival mass consistent with isolated ocular sarcoidosis. Keywords: Sarcoidosis, Ocular sarcoidosis, Immune thrombocytopenic purpura, ITP
INTRODUCTION
aspect of her right eye. This was noted incidentally and was asymptomatic, including no diplopia, pain, or changes in vision. The lesion size was stable over this period of observation. She was healthy other than a remote history of immune thrombocytopenic purpura (ITP) at the age of 5 when she presented with petechiae and ecchymosis and a platelet count of 3k. This was treated with a course of intravenous Rho(D) immunoglobulin (anti-D), a treatment for Rhþ patients with ITP, which led to a normalization of the platelet count and she has not had recurrence of ITP. On examination, she was 20/20 in both eyes. Her extraocular movements were full and there was no proptosis. A pinkish mildly elevated nodular lesion was present underneath the conjunctiva located inferotemporally on the right eye (Figure 1). A biopsy was obtained that showed multinucleated giant cells, epithelioid histiocytes, lymphocytes, and plasma cells consistent with granulomatous inflammation (Figure 2). Acid-fast bacillus and Gomori’s methenamine silver stain were both negative. Immunohistochemistry showed no clonal population to suggest lymphoma. A systemic workup revealed an elevated serum angiotensin converting enzyme (ACE) at 77 units/L (8–52 units/L). The rest of the workup was
Ocular sarcoidosis is one of the most common extrapulmonary manifestations of sarcoidosis, occurring in 22–47% of patients,1,2 and can present years or even decades before other manifestations of sarcoidosis. The most common ocular manifestations are uveitis and conjunctival nodules.1,2 In addition, sarcoidosis is associated with multiple hematologic abnormalities, including thrombocytopenia, which is seen in 1.9% of patients with sarcoidosis.3 Many cases of thrombocytopenia associated with sarcoidosis are thought to be due to a production of autoantibodies against platelet antigens analogous to that seen in idiopathic immune thrombocytopenic purpura.4–6 Althought this rare association between sarcoidosis and immune thrombocytopenia has been well described in the past, immune thrombocytopenia has not been reported in isolated ocular sarcoidosis.4–8 We present a patient with a remote history of immune thrombocytopenic purpura, who developed a conjunctival nodule consistent with isolated ocular sarcoidosis.
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1
CASE REPORT An 18-year-old Caucasian female presented with a 6-month history of a peribulbar lesion on the lateral
Received 14 April 2013; Revised 11 June 2013; Accepted 30 August 2013; Published online 21 October 2013 Correspondence: Richard C. Allen, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA, Tel: 319-356-2590, Fax: 319-356-0363, E-mail: [email protected]
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Ocular Sarcoidosis and Immune Thrombocytopenia
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unremarkable, including a normal chest radiograph (CXR), pulmonary function tests, complete blood count, anti-neutrophil cytoplasmic antibody, rapid plasma reagin, fluorescent treponemal antibodyabsorption, and fungal serologies. Because of the finding of non-caseating granulomas, elevated serum ACE, and remote history of ITP, we believe this lesion was consistent with ocular sarcoidosis. The patient was given an injection of subconjunctival, intralesional steroids consisting of 20 mg triamcinolone and 5 mg dexamethasone, which led to resolution of the lesion.
FIGURE 1. An elevated nodular lesion is present inferotemporally on the right eye.
FIGURE 2. Biopsy shows multinucleated giant cells, epithelioid histiocytes, lymphocytes, and plasma cells consistent with granulomatous inflammation.
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Comment Thrombocytopenia associated with sarcoidosis, which has been reported in 1.9% of patients, is thought to be caused by three mechanisms: hypersplenomegaly, bone marrow infiltration, and autoimmune.5,6 Both splenomegaly and bone marrow granulomatous infiltration tend to cause a mild thrombocytopenia, often with associated mild anemia and leukopenia.5,6 In contrast, immune thrombocytopenia associated with sarcoidosis can be severe and even lead to mortality if left untreated.5,7 Hemorrhage and thrombocytopenia can rarely even be the presenting sign of sarcoidosis.7 Immune thrombocytopenia can present before, after, or concurrently with sarcoidosis. In one study by Mahevas et al, sarcoidosis preceded immune thrombocytopenia in 55% of cases (median interval 4 years, range 6–216 months), immune thrombocytopenia preceded sarcoidosis in 25% of cases (median interval 5.67 years, range 15–153 months), and sarcoidosis and immune thrombocytopenia presented concurrently in 20% of cases.8 In our patient, there was an interval of 13 years between ITP resolution and presentation of sarcoidosis, which falls on the upper end of what has been reported in the past. Although the presence of the two diseases in our patient by coincidence cannot be ruled out, the relative rarity of the two diseases makes this less likely. The annual incidence of sarcoidosis ranges from 1–40 per 100,000,9 while the annual incidence of ITP ranges from 1.9–6.4 per 100,000.10 Therefore, the authors estimate the annual incidence of chance association between sarcoidosis and ITP ranges from about 1 per 100 million and 1 per 10 billion. The cause for the association between immune thrombocytopenia and sarcoidosis is still largely unknown.8 The pathogenesis of sarcoidosis and immune thrombocytopenia both involve an exuberant cell-mediated response, either to an unknown antigen in the case of sarcoidosis or to autologous platelet antigens in the case of ITP. It is likely that affected patients are predisposed to both sarcoidosis and ITP by some unknown mediator of autoimmunity that leads to the susceptibility to both diseases. Because immune thrombocytopenia associated with sarcoidosis can be severe and even fatal, it is important to be aware of this rare association between the two diseases.
DECLARATION OF INTEREST This research was funded in part by an unrestricted grant from
64 J. J. Chen and R. C. Allen
Research to Prevent Blindness, New York, NY. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES
Orbit Downloaded from informahealthcare.com by Kainan University on 04/28/15 For personal use only.
1. Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol 1978;86(5):648–655. 2. Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J Ophthalmol 1986;102(3):297–301. 3. Mayock RL, Bertrand P, Morrison CE, Scott JH. Manifestations of Sarcoidosis. Analysis of 145 patients, with a review of nine series selected from the literature. Am J Med 1963;35:67–89.
4. Lawrence HJ, Greenberg BR. Autoimmune thrombocytopenia in sarcoidosis. Am J Med 1985;79(6):761–764. 5. Dickerman JD, Holbrook PR, Zinkham WH. Etiology and therapy of thrombocytopenia associated with sarcoidosis. J Pediatr 1972;81(4):758–764. 6. Mahevas M, Le Page L, Salle V, et al. Thrombocytopenia in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis Oct 2006; 23(3):229–235. 7. Knodel AR, Beekman JF. Severe thrombocytopenia and sarcoidosis. JAMA 1980;243(3):258–259. 8. Mahevas M, Chiche L, Uzunhan Y, et al. Association of sarcoidosis and immune thrombocytopenia: presentation and outcome in a series of 20 patients. Medicine (Baltimore) 2011;90(4):269–278. 9. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007;357(21):2153–2165. 10. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol 2010;85(3):174–180.
Orbit
C ASE REPORT
Ocular Sarcoidosis and Immune Thrombocytopenia: A Rare Association John J. Chen1 and Richard C. Allen1,2 Department of Ophthalmology and Visual Sciences and 2Department of Otolaryngology – Head and Neck Surgery, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
ABSTRACT There is an association between sarcoidosis and immune thrombocytopenia, which can be severe and even fatal if left untreated. Although ocular sarcoidosis is one of the most common extrapulmonary manifestations of sarcoidosis, immune thrombocytopenia has not been reported in isolated ocular sarcoidosis. We present a patient with a remote history of immune thrombocytopenic purpura who developed a sub-conjunctival mass consistent with isolated ocular sarcoidosis. Keywords: Sarcoidosis, Ocular sarcoidosis, Immune thrombocytopenic purpura, ITP
INTRODUCTION
aspect of her right eye. This was noted incidentally and was asymptomatic, including no diplopia, pain, or changes in vision. The lesion size was stable over this period of observation. She was healthy other than a remote history of immune thrombocytopenic purpura (ITP) at the age of 5 when she presented with petechiae and ecchymosis and a platelet count of 3k. This was treated with a course of intravenous Rho(D) immunoglobulin (anti-D), a treatment for Rhþ patients with ITP, which led to a normalization of the platelet count and she has not had recurrence of ITP. On examination, she was 20/20 in both eyes. Her extraocular movements were full and there was no proptosis. A pinkish mildly elevated nodular lesion was present underneath the conjunctiva located inferotemporally on the right eye (Figure 1). A biopsy was obtained that showed multinucleated giant cells, epithelioid histiocytes, lymphocytes, and plasma cells consistent with granulomatous inflammation (Figure 2). Acid-fast bacillus and Gomori’s methenamine silver stain were both negative. Immunohistochemistry showed no clonal population to suggest lymphoma. A systemic workup revealed an elevated serum angiotensin converting enzyme (ACE) at 77 units/L (8–52 units/L). The rest of the workup was
Ocular sarcoidosis is one of the most common extrapulmonary manifestations of sarcoidosis, occurring in 22–47% of patients,1,2 and can present years or even decades before other manifestations of sarcoidosis. The most common ocular manifestations are uveitis and conjunctival nodules.1,2 In addition, sarcoidosis is associated with multiple hematologic abnormalities, including thrombocytopenia, which is seen in 1.9% of patients with sarcoidosis.3 Many cases of thrombocytopenia associated with sarcoidosis are thought to be due to a production of autoantibodies against platelet antigens analogous to that seen in idiopathic immune thrombocytopenic purpura.4–6 Althought this rare association between sarcoidosis and immune thrombocytopenia has been well described in the past, immune thrombocytopenia has not been reported in isolated ocular sarcoidosis.4–8 We present a patient with a remote history of immune thrombocytopenic purpura, who developed a conjunctival nodule consistent with isolated ocular sarcoidosis.
20 14
Orbit Downloaded from informahealthcare.com by Kainan University on 04/28/15 For personal use only.
1
CASE REPORT An 18-year-old Caucasian female presented with a 6-month history of a peribulbar lesion on the lateral
Received 14 April 2013; Revised 11 June 2013; Accepted 30 August 2013; Published online 21 October 2013 Correspondence: Richard C. Allen, Department of Ophthalmology and Visual Sciences, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USA, Tel: 319-356-2590, Fax: 319-356-0363, E-mail: [email protected]
62
Ocular Sarcoidosis and Immune Thrombocytopenia
Orbit Downloaded from informahealthcare.com by Kainan University on 04/28/15 For personal use only.
unremarkable, including a normal chest radiograph (CXR), pulmonary function tests, complete blood count, anti-neutrophil cytoplasmic antibody, rapid plasma reagin, fluorescent treponemal antibodyabsorption, and fungal serologies. Because of the finding of non-caseating granulomas, elevated serum ACE, and remote history of ITP, we believe this lesion was consistent with ocular sarcoidosis. The patient was given an injection of subconjunctival, intralesional steroids consisting of 20 mg triamcinolone and 5 mg dexamethasone, which led to resolution of the lesion.
FIGURE 1. An elevated nodular lesion is present inferotemporally on the right eye.
FIGURE 2. Biopsy shows multinucleated giant cells, epithelioid histiocytes, lymphocytes, and plasma cells consistent with granulomatous inflammation.
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2014 Informa Healthcare USA, Inc.
63
Comment Thrombocytopenia associated with sarcoidosis, which has been reported in 1.9% of patients, is thought to be caused by three mechanisms: hypersplenomegaly, bone marrow infiltration, and autoimmune.5,6 Both splenomegaly and bone marrow granulomatous infiltration tend to cause a mild thrombocytopenia, often with associated mild anemia and leukopenia.5,6 In contrast, immune thrombocytopenia associated with sarcoidosis can be severe and even lead to mortality if left untreated.5,7 Hemorrhage and thrombocytopenia can rarely even be the presenting sign of sarcoidosis.7 Immune thrombocytopenia can present before, after, or concurrently with sarcoidosis. In one study by Mahevas et al, sarcoidosis preceded immune thrombocytopenia in 55% of cases (median interval 4 years, range 6–216 months), immune thrombocytopenia preceded sarcoidosis in 25% of cases (median interval 5.67 years, range 15–153 months), and sarcoidosis and immune thrombocytopenia presented concurrently in 20% of cases.8 In our patient, there was an interval of 13 years between ITP resolution and presentation of sarcoidosis, which falls on the upper end of what has been reported in the past. Although the presence of the two diseases in our patient by coincidence cannot be ruled out, the relative rarity of the two diseases makes this less likely. The annual incidence of sarcoidosis ranges from 1–40 per 100,000,9 while the annual incidence of ITP ranges from 1.9–6.4 per 100,000.10 Therefore, the authors estimate the annual incidence of chance association between sarcoidosis and ITP ranges from about 1 per 100 million and 1 per 10 billion. The cause for the association between immune thrombocytopenia and sarcoidosis is still largely unknown.8 The pathogenesis of sarcoidosis and immune thrombocytopenia both involve an exuberant cell-mediated response, either to an unknown antigen in the case of sarcoidosis or to autologous platelet antigens in the case of ITP. It is likely that affected patients are predisposed to both sarcoidosis and ITP by some unknown mediator of autoimmunity that leads to the susceptibility to both diseases. Because immune thrombocytopenia associated with sarcoidosis can be severe and even fatal, it is important to be aware of this rare association between the two diseases.
DECLARATION OF INTEREST This research was funded in part by an unrestricted grant from
64 J. J. Chen and R. C. Allen
Research to Prevent Blindness, New York, NY. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
REFERENCES
Orbit Downloaded from informahealthcare.com by Kainan University on 04/28/15 For personal use only.
1. Obenauf CD, Shaw HE, Sydnor CF, Klintworth GK. Sarcoidosis and its ophthalmic manifestations. Am J Ophthalmol 1978;86(5):648–655. 2. Jabs DA, Johns CJ. Ocular involvement in chronic sarcoidosis. Am J Ophthalmol 1986;102(3):297–301. 3. Mayock RL, Bertrand P, Morrison CE, Scott JH. Manifestations of Sarcoidosis. Analysis of 145 patients, with a review of nine series selected from the literature. Am J Med 1963;35:67–89.
4. Lawrence HJ, Greenberg BR. Autoimmune thrombocytopenia in sarcoidosis. Am J Med 1985;79(6):761–764. 5. Dickerman JD, Holbrook PR, Zinkham WH. Etiology and therapy of thrombocytopenia associated with sarcoidosis. J Pediatr 1972;81(4):758–764. 6. Mahevas M, Le Page L, Salle V, et al. Thrombocytopenia in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis Oct 2006; 23(3):229–235. 7. Knodel AR, Beekman JF. Severe thrombocytopenia and sarcoidosis. JAMA 1980;243(3):258–259. 8. Mahevas M, Chiche L, Uzunhan Y, et al. Association of sarcoidosis and immune thrombocytopenia: presentation and outcome in a series of 20 patients. Medicine (Baltimore) 2011;90(4):269–278. 9. Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007;357(21):2153–2165. 10. Terrell DR, Beebe LA, Vesely SK, et al. The incidence of immune thrombocytopenic purpura in children and adults: A critical review of published reports. Am J Hematol 2010;85(3):174–180.
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