- Email: [email protected]
What is your diagnosis?
Indian Journal of Rheumatology 2008 September Volume 3, Number 3; pp. 125–127
PG Forum
What is your diagnosis? A 16-year old girl with venous thrombosis at an unusual site of 5 months duration R Sharma, J Kishore, S Agrawal, L Rajasekhar, GG Narsimulu
A 16-year-old girl presented with cough and expectoration associated with dyspnoea, left-sided chest pain and fever in November 2006. Her chest radiograph showed bilateral, nonhomogeneous opacities which disappeared after 1 week of antibiotic therapy. A month later, she developed pain over left suprascapular region spreading on to left side of the neck and left supraclavicular region progressively increasing over 2 days. This was associated with fullness and the overlying skin became tight and glossy along with puffiness over the face. There was no history of weight loss, alopecia, malar rash, myalgia, polyarthralgia, oral ulcers, photosensitivity or Raynaud’s phenomenon. There was no history of haemoptysis, smoky urine or abdominal pain. There was no history of any abnormal motor or sensory symptoms. There was no history of hypertension or asthma. There was no history suggestive of sinusitis. Investigations revealed mild anaemia (Hb 11 gm/dL) and thrombocytosis (platelets 500,000/cu mm). Total leucocyte count was normal (11,000/cu mm) with moderate eosinophilia (24%) and ESR was 42 mm/first hr. Urine and serum creatinine were normal. ANA was negative. Magnetic resonance imaging was done which revealed thrombosis of the left internal jugular and left subclavian veins, which was confirmed by colour Doppler. To rule out hypercoagulable state protein C and protein S, antithrombin III, homocysteine and Factor V Leiden were done, which were all found to be within normal limits. Anticardiolipin antibodies (IgG and IgM) were also negative. The patient was started on anticoagulants and a course of antibiotics. Five months later, in March 2007 (when she was seen by us for the first time), she developed reddish purple discoloration of the tips of the fingers, toes and over the soles. She also complained of diminution of vision and recurrence of puffiness of face. On high resolution ultrasound of neck, small size left supraclavicular adenopathy was detected. In view of, history dating back to 5 months with the previous
Figure 1 Multiple bilateral frontoparietooccipital hyperintensities in T2 and FLAIR suggestive of vasculitis.
chest x-ray findings and now recurrence with fresh symptoms, HRCT chest was done which was suggestive of patchy areas of ground glass haziness in right upper, bilateral lower and right middle lobe, and mediastinal adenopathy. MRI brain showed multiple hyperintensities in T2 and FLAIR involving bilateral frontoparietal and occipital lobes (Figure 1). EBV serology, both IgG and IgM were positive. A lymph node biopsy was done (Figure 2).
ANSWER Lymph node biopsy showed obliteration of architecture with focally preserved sinuses. Pleomorphic infiltrate of lymphoid
Department of Rheumatology, Nizam’s Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India. Correspondence: Prof GG Narsimulu, email: [email protected]
126
Indian Journal of Rheumatology 2008 September; Vol. 3, No. 3
Figure 2 Angiocentric and angiodestructive lesions with lymphocytic infiltrates.
cell in paracortical area consisting of lymphocytes, plasma cells and plasmacytoid cells and occasional eosinophils and immunoblasts were seen. The latter were also seen in aggregates. Angiocentric and angiodestructive lesions with lymphocytic infiltrates which are characteristic of lymphomatoid granulomatosis were seen. Proliferation of blood vessels was seen throughout the lymph node. Normal germinal centres were replaced by loose aggregates of immunoblasts and pale histiocytes. Extravasation of RBCs and proliferation of histiocytes could be seen. Thus a diagnosis of lymphomatoid granulomatosis was made. Our patient presented with a rare finding of venous thrombosis at an unusual site (left internal jugular and subclavian) associated with other systemic features consistent with lymphomatoid granulomatosis. After a thorough medline search we did not come across such a presentation. She was treated with pulse methylprednisolone and cyclophosphamide. After 6 months she reported significant improvement with disappearance of rashes, improvement in the distant vision and pulmonary symptoms. In follow up, she is doing well with no recurrence in symptoms. Lymphomatoid granulomatosis is a rare EBV virus associated systemic angiodestructive lymphoproliferative disease. It is a mimic of vasculitis and occasionally a forerunner of malignant lymphoproliferative disease.1 It is characterized by prominent pulmonary involvement but can also involve multiple extrapulmonary sites.1 The diagnosis is based on histological triad of (i) nodular polymorphic lymphoid infiltrate composed of small lymphocytes, plasma cells and variable number of large atypical mononuclear cells (ii) angiitis due to transmural infiltration of arteries and veins by lymphocytes (iii) granulomatosis.2 LG is usually progressive
Sharma et al.
and fatal disorder. The clinical course is variable, and there are some reports of spontaneous regression.3 No known racial predilection has been seen. The male to female ratio is 2:1 and it is common after the fifth and sixth decades of life, although cases ranging from 3 years to 92 years have been reported.3 LG is systemic multi-organ disease most commonly involving lungs (80%) followed by skin (50%) and nervous system (25%). Kidney and liver are less commonly involved. Lymph node, spleen and bone marrow are usually spared until late in the course of illness.2 No characteristic laboratory abnormalities exist. Chest radiographs are usually abnormal but non-specific. CT scan defines pulmonary lesions very well but findings are non-specific.3 The therapeutic approach and optimal management have not been well defined. In several studies, therapy has ranged from observation to treatment with prednisone or chemotherapy. In the largest reported study of 152 patients, no significant difference in mortality or disease-free survival was found with treatment, and the mortality rate exceeded 50%.4 New therapeutic approaches are necessary. In view of the association of LG with EBV and the similarity to post-transplant lymphoma, the use of antiviral drugs with minimal immunosuppressive therapy is advocated.2 For patients with more aggressive disease treatment of lymphoma with chemotherapy such as CHOP is appropriate.5 There is another case report of successful treatment of advanced lymphomatoid granulomatosis with rituximab-CVP combination therapy.6 Our patient was treated with pulse methylprednisolone and cyclophosphamide. She responded well to the treatment and is symptom free 6 months after the completion of therapy.
ACKNOWLEDGEMENTS Source of Funding: Nil. Disclosure statement: Author has declared no conflict of interest.
REFERENCES 1.
2.
Guinnee D Jr, Jaffe E, Kingma D, Fishback N, Wallberg K, Krishnan J, et al. Pulmonary lymphomatoid granulomatosis: evidence for a proliferation of Ebstein–Barr virus infected B-lymphocytes with a prominent T-cell component and vasculitis. Am J Surg Pathol 1994; 18: 753–64. Laibow AA, Carrington CR, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol 1972; 3: 457–558.
What is your diagnosis?
3.
4.
PG Forum
Heslop HE. Biology and treatment of Ebstein Barr virus associated non-Hodgkin’s lymphomas. Hematology Am Soc Hematol Educ Program. 2005; 260–6. Wu SM, Min Y, Ostrzega N, Clements PJ, Wong AL. Lymphomatoid granulomatosis: rare mimicker of vasculitis. J Rheumatol 2005; 32: 2242–5.
5.
Jafee EH, Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv 1997; 30: 233–48. Hu YH, Liu CY, Chiu CH, Hsiao LT. Successful treatment of elderly advanced lymphomatoid granulomatosis with rituximabCVP combination therapy. Eur J Haematol 2007; 78: 176–7.
6.
***
ANSWERS TO THE RHEUMATOLOGY QUIZ (page 124) 1c*, 2c**, 3a***, 4b†, 5d††, 6c, 7b, 8d†††, 9a, 10b¥ * First described in 1924, can be used in haemophiliac joints, uses beta-emitters. ** The rash characteristically involves the anterior leg and the dorsum of the feet.
In a dose of 800 mg/day, HCQ was equal to zidovudine in controlling viral replication in HIV-infected patients. † Fever is equally common in both. All the others are more common with TNF antagonist induced DIL. †† Phagocytosis is impaired in SLE. ††† Fluoroquinolones have been implicated in causing tendinopathy and tendon rupture. ¥ Tocilizumab acts against interleukin 6 receptor (IL-6R).
INDIAN RHEUMATOLOGY ASSOCIATION CONFERENCE I R A
26–29 Nov 2008
Register at www.puneiracon2008.org Along with: THE BONE & JOINT DECADE INDIA CONVENTION 29–30 Nov 2008 & WORLD NETWORK MEET (28 Nov–01 Dec 2008) Register at www.bjdindia.org
50 Travel Bursaries Available Contact: Arvind Chopra, MD Organizing Secretary Email: [email protected]
127
Rheumatologists, Orthopedic Surgeons, & Physicians
PG Forum
What is your diagnosis? A 16-year old girl with venous thrombosis at an unusual site of 5 months duration R Sharma, J Kishore, S Agrawal, L Rajasekhar, GG Narsimulu
A 16-year-old girl presented with cough and expectoration associated with dyspnoea, left-sided chest pain and fever in November 2006. Her chest radiograph showed bilateral, nonhomogeneous opacities which disappeared after 1 week of antibiotic therapy. A month later, she developed pain over left suprascapular region spreading on to left side of the neck and left supraclavicular region progressively increasing over 2 days. This was associated with fullness and the overlying skin became tight and glossy along with puffiness over the face. There was no history of weight loss, alopecia, malar rash, myalgia, polyarthralgia, oral ulcers, photosensitivity or Raynaud’s phenomenon. There was no history of haemoptysis, smoky urine or abdominal pain. There was no history of any abnormal motor or sensory symptoms. There was no history of hypertension or asthma. There was no history suggestive of sinusitis. Investigations revealed mild anaemia (Hb 11 gm/dL) and thrombocytosis (platelets 500,000/cu mm). Total leucocyte count was normal (11,000/cu mm) with moderate eosinophilia (24%) and ESR was 42 mm/first hr. Urine and serum creatinine were normal. ANA was negative. Magnetic resonance imaging was done which revealed thrombosis of the left internal jugular and left subclavian veins, which was confirmed by colour Doppler. To rule out hypercoagulable state protein C and protein S, antithrombin III, homocysteine and Factor V Leiden were done, which were all found to be within normal limits. Anticardiolipin antibodies (IgG and IgM) were also negative. The patient was started on anticoagulants and a course of antibiotics. Five months later, in March 2007 (when she was seen by us for the first time), she developed reddish purple discoloration of the tips of the fingers, toes and over the soles. She also complained of diminution of vision and recurrence of puffiness of face. On high resolution ultrasound of neck, small size left supraclavicular adenopathy was detected. In view of, history dating back to 5 months with the previous
Figure 1 Multiple bilateral frontoparietooccipital hyperintensities in T2 and FLAIR suggestive of vasculitis.
chest x-ray findings and now recurrence with fresh symptoms, HRCT chest was done which was suggestive of patchy areas of ground glass haziness in right upper, bilateral lower and right middle lobe, and mediastinal adenopathy. MRI brain showed multiple hyperintensities in T2 and FLAIR involving bilateral frontoparietal and occipital lobes (Figure 1). EBV serology, both IgG and IgM were positive. A lymph node biopsy was done (Figure 2).
ANSWER Lymph node biopsy showed obliteration of architecture with focally preserved sinuses. Pleomorphic infiltrate of lymphoid
Department of Rheumatology, Nizam’s Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India. Correspondence: Prof GG Narsimulu, email: [email protected]
126
Indian Journal of Rheumatology 2008 September; Vol. 3, No. 3
Figure 2 Angiocentric and angiodestructive lesions with lymphocytic infiltrates.
cell in paracortical area consisting of lymphocytes, plasma cells and plasmacytoid cells and occasional eosinophils and immunoblasts were seen. The latter were also seen in aggregates. Angiocentric and angiodestructive lesions with lymphocytic infiltrates which are characteristic of lymphomatoid granulomatosis were seen. Proliferation of blood vessels was seen throughout the lymph node. Normal germinal centres were replaced by loose aggregates of immunoblasts and pale histiocytes. Extravasation of RBCs and proliferation of histiocytes could be seen. Thus a diagnosis of lymphomatoid granulomatosis was made. Our patient presented with a rare finding of venous thrombosis at an unusual site (left internal jugular and subclavian) associated with other systemic features consistent with lymphomatoid granulomatosis. After a thorough medline search we did not come across such a presentation. She was treated with pulse methylprednisolone and cyclophosphamide. After 6 months she reported significant improvement with disappearance of rashes, improvement in the distant vision and pulmonary symptoms. In follow up, she is doing well with no recurrence in symptoms. Lymphomatoid granulomatosis is a rare EBV virus associated systemic angiodestructive lymphoproliferative disease. It is a mimic of vasculitis and occasionally a forerunner of malignant lymphoproliferative disease.1 It is characterized by prominent pulmonary involvement but can also involve multiple extrapulmonary sites.1 The diagnosis is based on histological triad of (i) nodular polymorphic lymphoid infiltrate composed of small lymphocytes, plasma cells and variable number of large atypical mononuclear cells (ii) angiitis due to transmural infiltration of arteries and veins by lymphocytes (iii) granulomatosis.2 LG is usually progressive
Sharma et al.
and fatal disorder. The clinical course is variable, and there are some reports of spontaneous regression.3 No known racial predilection has been seen. The male to female ratio is 2:1 and it is common after the fifth and sixth decades of life, although cases ranging from 3 years to 92 years have been reported.3 LG is systemic multi-organ disease most commonly involving lungs (80%) followed by skin (50%) and nervous system (25%). Kidney and liver are less commonly involved. Lymph node, spleen and bone marrow are usually spared until late in the course of illness.2 No characteristic laboratory abnormalities exist. Chest radiographs are usually abnormal but non-specific. CT scan defines pulmonary lesions very well but findings are non-specific.3 The therapeutic approach and optimal management have not been well defined. In several studies, therapy has ranged from observation to treatment with prednisone or chemotherapy. In the largest reported study of 152 patients, no significant difference in mortality or disease-free survival was found with treatment, and the mortality rate exceeded 50%.4 New therapeutic approaches are necessary. In view of the association of LG with EBV and the similarity to post-transplant lymphoma, the use of antiviral drugs with minimal immunosuppressive therapy is advocated.2 For patients with more aggressive disease treatment of lymphoma with chemotherapy such as CHOP is appropriate.5 There is another case report of successful treatment of advanced lymphomatoid granulomatosis with rituximab-CVP combination therapy.6 Our patient was treated with pulse methylprednisolone and cyclophosphamide. She responded well to the treatment and is symptom free 6 months after the completion of therapy.
ACKNOWLEDGEMENTS Source of Funding: Nil. Disclosure statement: Author has declared no conflict of interest.
REFERENCES 1.
2.
Guinnee D Jr, Jaffe E, Kingma D, Fishback N, Wallberg K, Krishnan J, et al. Pulmonary lymphomatoid granulomatosis: evidence for a proliferation of Ebstein–Barr virus infected B-lymphocytes with a prominent T-cell component and vasculitis. Am J Surg Pathol 1994; 18: 753–64. Laibow AA, Carrington CR, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol 1972; 3: 457–558.
What is your diagnosis?
3.
4.
PG Forum
Heslop HE. Biology and treatment of Ebstein Barr virus associated non-Hodgkin’s lymphomas. Hematology Am Soc Hematol Educ Program. 2005; 260–6. Wu SM, Min Y, Ostrzega N, Clements PJ, Wong AL. Lymphomatoid granulomatosis: rare mimicker of vasculitis. J Rheumatol 2005; 32: 2242–5.
5.
Jafee EH, Wilson WH. Lymphomatoid granulomatosis: pathogenesis, pathology and clinical implications. Cancer Surv 1997; 30: 233–48. Hu YH, Liu CY, Chiu CH, Hsiao LT. Successful treatment of elderly advanced lymphomatoid granulomatosis with rituximabCVP combination therapy. Eur J Haematol 2007; 78: 176–7.
6.
***
ANSWERS TO THE RHEUMATOLOGY QUIZ (page 124) 1c*, 2c**, 3a***, 4b†, 5d††, 6c, 7b, 8d†††, 9a, 10b¥ * First described in 1924, can be used in haemophiliac joints, uses beta-emitters. ** The rash characteristically involves the anterior leg and the dorsum of the feet.
In a dose of 800 mg/day, HCQ was equal to zidovudine in controlling viral replication in HIV-infected patients. † Fever is equally common in both. All the others are more common with TNF antagonist induced DIL. †† Phagocytosis is impaired in SLE. ††† Fluoroquinolones have been implicated in causing tendinopathy and tendon rupture. ¥ Tocilizumab acts against interleukin 6 receptor (IL-6R).
INDIAN RHEUMATOLOGY ASSOCIATION CONFERENCE I R A
26–29 Nov 2008
Register at www.puneiracon2008.org Along with: THE BONE & JOINT DECADE INDIA CONVENTION 29–30 Nov 2008 & WORLD NETWORK MEET (28 Nov–01 Dec 2008) Register at www.bjdindia.org
50 Travel Bursaries Available Contact: Arvind Chopra, MD Organizing Secretary Email: [email protected]
127
Rheumatologists, Orthopedic Surgeons, & Physicians