International Journal of Rheumatic Diseases 2013; 16: 762–763
CORRESPONDENCE
Rheumatoid arthritis with increased bone mineral density Dear Editor, A 40-year-old woman presented with pain in both hands and feet of about 2 years duration associated with early morning stiffness of about 15 min. She did not complain of swelling of any joint, backache, photosensitivity, skin involvement or lack of sleep. She did not give a past history of any significant ailment such as tuberculosis or associated illness such as hypothyroidism, hypertension or diabetes. She gave a family history of dense white bones on X-ray. Her brother had a fracture which healed over 5 years. Her sister suffered from anemia and splenomegaly. A bone marrow biopsy planned for her sister was unsuccessful due to the tough bones. She had three sons who did not suffer from any known disease. Water supply from the area where she resided had permitted levels of flouride. There was no history of exposure to beryllium, lead or bismuth. On examination, the patient was found to be hypertensive. She was not pale and other findings on general examination were also within normal limits. Musculoskeletal examination revealed two actively inflamed proximal interphalangeal joints. Systemic examination was within normal limits. Investigations revealed mild normocytic, normochromic anemia with normal leukocyte and platelet counts (Table 1). Her rheumatoid factor and anti-citrullinated protein antibody (ACPA) immunoglobulin G were positive. She had normal thyroid profile, renal functions and liver functions. X-ray of the hand did not show juxta-articular osteoporosis or erosion but showed patchy increase in bone density. There was diffuse sclerosis of the spine, pelvis and appendicular bones. Focal sclerosis of vertebral end plates was seen giving it a ‘sandwich’ vertebrae appearance (Rugger Jersey spine; Fig. 1). Diffuse sclerotic changes in visualized vertebrae, sternum and proximal part of bilateral humerus were seen, even in high-resolution computed tomography of the chest which revealed dense fibrosis with foci of coarse calcifications in the posterior segment of the right upper lobe with tractional bronchiectasis and emphysematous changes with tubular bronchiectatic changes in both lungs with calcified subcranial lymph nodes. Ultrasonography of
the abdomen revealed normal kidney size and echotexture. Bone mineral density (BMD) revealed T-scores of +3.6 and +7.1 at the femur (mean) and anteroposterior spine, respectively. Bone marrow examination and bone biopsy were not done because the patient did not give consent for the same as a similar procedure had failed in her sister and had caused a lot of pain. The patient was diagnosed as a case of autosomal dominant osteopetrosis (ADO) with rheumatoid arthritis. Her symptoms responded well to low-dose steroids, methotrexate and hydroxychloroquine. Osteopetrosis is a rare congenital disorder of the skeletal system. Also known as ‘marble bone disease’ it is characterized by increased bone density. Several types of osteopetrosis are described based on clinical features, mode of inheritance and underlying molecular and pathogenetic mechanisms.1 The common pathogenetic factor among them is abnormal osteoclast-mediated bone resorption leading to osteosclerosis.2,3 Autosomal recessive osteopetrosis (ARO) presents within the first few months of life and is often lethal because of complications arising from bone marrow obliteration.1
Table 1 Patient’s laboratory results Test Hemoglobin (mmol/L) MCV (fL) MCH (pg) TLC (n 9 109/L) Platelet count (n 9 109/L) ESR (Westergren) (mm/h) Serum calcium (mmol/L) Serum ALP (U/L) Serum PTH (ng/L) Serum 25(OH)D (nmol/L) Rheumatoid factor ACPA IgG (U/mL)
Result
Reference range
6.4 87.9 29.8 5.71 112 50 2.35 259.3 53.9 68.6 Positive 1092.64
7.4–9.9 78–102 26–34 4.5–11 100–350 1–25 2.2–2.6 64–306 10–60 75–175 Negative < 15
ACPA, anti-citrullinated protein antibodies; ALP, alkaline phosphatase; ESR, erythrocyte sedimentation rate; IgG, immunoglobulin G; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; PTH, parathyroid hormone; TLC, total leucocyte count; 25(OH) D, 25-hydroxyvitamin D.
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
(a)
(b)
(c)
(d)
Figure 1 (a) X-ray of the lumbar spine, anteroposterior view and (b) X-ray of the lumbar spine lateral view, showing focal sclerosis of vertebral end plates giving it a ‘sandwich’ vertebrae appearance (Rugger–Jersey spine) along with loss of lumbar lordosis. (c) X-ray of bilateral hands postero-anterior view shows patchy increase in bone density. It does not show any juxta-articular osteopenia or erosion. (d) X-ray of bilateral forearms anteroposterior view shows patchy increase in bone density and thick cortex of both radius and ulna bilaterally. Interosseous membrane on both sides does not show any calcification.
ADO is a benign type having a delayed onset, usually in late childhood or adolescence. Also known as ‘AlbersSchonberg disease’ it may be asymptomatic or may present with pathologic fractures, mild anemia or cranial nerve palsies. ‘Sandwich vertebrae’ (dense bands of sclerosis parallel to vertebral end plates) is the classically described radiographic sign.1 Another type, intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course.4 Symptomatic care remains the mainstay of treatment, although bone marrow transplantation can be used in severe forms.1,4 High-dose calcitriol can be used to stimulate osteoclast differentiation.4 The diagnosis of osteopetrosis in this patient was suspected due to strikingly high T-scores on BMD and confirmed by classic ‘sandwich vertebrae’ appearance on radiographs of the lumbosacral spine along with a positive family history, even though bone marrow examination and bone biopsy were not done. An association with rheumatoid arthritis was considered due to involvement of two actively inflamed small joints, duration of more than 6 weeks, a raised erythrocyte sedimentation rate and highly raised ACPA titres.
International Journal of Rheumatic Diseases 2013; 16: 762–763
Osteopetrosis in itself is a rare disorder and its association with rheumatoid arthritis is even less often reported, highlighting the importance of this case. Shweta AGARWAL and Siddharth K. DAS
Department of Rheumatology, King George Medical University, Lucknow, Uttar Pradesh, India Correspondence: Dr Shweta Agarwal, email: [email protected]
REFERENCES 1 Stark Z, Savarirayan R (2009) Osteopetrosis. Orphanet J Rare Dis 4, 5. 2 Albers-Schonberg HE (1904) Rontgenbilder einer seltenen Knochenerkrankung [in German]. Munch Med Wochenschr 51, 365. 3 Armstrong DG, Newfield JT, Gillespie R (1999) Orthopedic management of osteopetrosis: results of a survey and review of the literature. J Pediatr Orthop 19(1), 122–32. 4 Shapiro F (1993) Osteopetrosis: current clinical considerations. Clin Orthop Relat Res 294, 34–44.
763
CORRESPONDENCE
Rheumatoid arthritis with increased bone mineral density Dear Editor, A 40-year-old woman presented with pain in both hands and feet of about 2 years duration associated with early morning stiffness of about 15 min. She did not complain of swelling of any joint, backache, photosensitivity, skin involvement or lack of sleep. She did not give a past history of any significant ailment such as tuberculosis or associated illness such as hypothyroidism, hypertension or diabetes. She gave a family history of dense white bones on X-ray. Her brother had a fracture which healed over 5 years. Her sister suffered from anemia and splenomegaly. A bone marrow biopsy planned for her sister was unsuccessful due to the tough bones. She had three sons who did not suffer from any known disease. Water supply from the area where she resided had permitted levels of flouride. There was no history of exposure to beryllium, lead or bismuth. On examination, the patient was found to be hypertensive. She was not pale and other findings on general examination were also within normal limits. Musculoskeletal examination revealed two actively inflamed proximal interphalangeal joints. Systemic examination was within normal limits. Investigations revealed mild normocytic, normochromic anemia with normal leukocyte and platelet counts (Table 1). Her rheumatoid factor and anti-citrullinated protein antibody (ACPA) immunoglobulin G were positive. She had normal thyroid profile, renal functions and liver functions. X-ray of the hand did not show juxta-articular osteoporosis or erosion but showed patchy increase in bone density. There was diffuse sclerosis of the spine, pelvis and appendicular bones. Focal sclerosis of vertebral end plates was seen giving it a ‘sandwich’ vertebrae appearance (Rugger Jersey spine; Fig. 1). Diffuse sclerotic changes in visualized vertebrae, sternum and proximal part of bilateral humerus were seen, even in high-resolution computed tomography of the chest which revealed dense fibrosis with foci of coarse calcifications in the posterior segment of the right upper lobe with tractional bronchiectasis and emphysematous changes with tubular bronchiectatic changes in both lungs with calcified subcranial lymph nodes. Ultrasonography of
the abdomen revealed normal kidney size and echotexture. Bone mineral density (BMD) revealed T-scores of +3.6 and +7.1 at the femur (mean) and anteroposterior spine, respectively. Bone marrow examination and bone biopsy were not done because the patient did not give consent for the same as a similar procedure had failed in her sister and had caused a lot of pain. The patient was diagnosed as a case of autosomal dominant osteopetrosis (ADO) with rheumatoid arthritis. Her symptoms responded well to low-dose steroids, methotrexate and hydroxychloroquine. Osteopetrosis is a rare congenital disorder of the skeletal system. Also known as ‘marble bone disease’ it is characterized by increased bone density. Several types of osteopetrosis are described based on clinical features, mode of inheritance and underlying molecular and pathogenetic mechanisms.1 The common pathogenetic factor among them is abnormal osteoclast-mediated bone resorption leading to osteosclerosis.2,3 Autosomal recessive osteopetrosis (ARO) presents within the first few months of life and is often lethal because of complications arising from bone marrow obliteration.1
Table 1 Patient’s laboratory results Test Hemoglobin (mmol/L) MCV (fL) MCH (pg) TLC (n 9 109/L) Platelet count (n 9 109/L) ESR (Westergren) (mm/h) Serum calcium (mmol/L) Serum ALP (U/L) Serum PTH (ng/L) Serum 25(OH)D (nmol/L) Rheumatoid factor ACPA IgG (U/mL)
Result
Reference range
6.4 87.9 29.8 5.71 112 50 2.35 259.3 53.9 68.6 Positive 1092.64
7.4–9.9 78–102 26–34 4.5–11 100–350 1–25 2.2–2.6 64–306 10–60 75–175 Negative < 15
ACPA, anti-citrullinated protein antibodies; ALP, alkaline phosphatase; ESR, erythrocyte sedimentation rate; IgG, immunoglobulin G; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; PTH, parathyroid hormone; TLC, total leucocyte count; 25(OH) D, 25-hydroxyvitamin D.
© 2013 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd
Correspondence
(a)
(b)
(c)
(d)
Figure 1 (a) X-ray of the lumbar spine, anteroposterior view and (b) X-ray of the lumbar spine lateral view, showing focal sclerosis of vertebral end plates giving it a ‘sandwich’ vertebrae appearance (Rugger–Jersey spine) along with loss of lumbar lordosis. (c) X-ray of bilateral hands postero-anterior view shows patchy increase in bone density. It does not show any juxta-articular osteopenia or erosion. (d) X-ray of bilateral forearms anteroposterior view shows patchy increase in bone density and thick cortex of both radius and ulna bilaterally. Interosseous membrane on both sides does not show any calcification.
ADO is a benign type having a delayed onset, usually in late childhood or adolescence. Also known as ‘AlbersSchonberg disease’ it may be asymptomatic or may present with pathologic fractures, mild anemia or cranial nerve palsies. ‘Sandwich vertebrae’ (dense bands of sclerosis parallel to vertebral end plates) is the classically described radiographic sign.1 Another type, intermediate autosomal recessive, appears during the first decade of life but does not follow a malignant course.4 Symptomatic care remains the mainstay of treatment, although bone marrow transplantation can be used in severe forms.1,4 High-dose calcitriol can be used to stimulate osteoclast differentiation.4 The diagnosis of osteopetrosis in this patient was suspected due to strikingly high T-scores on BMD and confirmed by classic ‘sandwich vertebrae’ appearance on radiographs of the lumbosacral spine along with a positive family history, even though bone marrow examination and bone biopsy were not done. An association with rheumatoid arthritis was considered due to involvement of two actively inflamed small joints, duration of more than 6 weeks, a raised erythrocyte sedimentation rate and highly raised ACPA titres.
International Journal of Rheumatic Diseases 2013; 16: 762–763
Osteopetrosis in itself is a rare disorder and its association with rheumatoid arthritis is even less often reported, highlighting the importance of this case. Shweta AGARWAL and Siddharth K. DAS
Department of Rheumatology, King George Medical University, Lucknow, Uttar Pradesh, India Correspondence: Dr Shweta Agarwal, email: [email protected]
REFERENCES 1 Stark Z, Savarirayan R (2009) Osteopetrosis. Orphanet J Rare Dis 4, 5. 2 Albers-Schonberg HE (1904) Rontgenbilder einer seltenen Knochenerkrankung [in German]. Munch Med Wochenschr 51, 365. 3 Armstrong DG, Newfield JT, Gillespie R (1999) Orthopedic management of osteopetrosis: results of a survey and review of the literature. J Pediatr Orthop 19(1), 122–32. 4 Shapiro F (1993) Osteopetrosis: current clinical considerations. Clin Orthop Relat Res 294, 34–44.
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