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Drug rash with eosinophilia and systemic symptoms syndrome induced by sulfasalazine
Letters to the editor / Joint Bone Spine 77 (2010) 81–89 [10] van der Linden S, Valkenburg HA, Cats A. Evaluation of diagnostic criteria for ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis Rheum 1984;27:361–8.
Ismail Sari a,∗ Ahmet Alacacioglu a Levent Kebapcilar a Ali Taylan b Oktay Bilgir a Yasar Yildiz a Arif Yuksel a Didem L. Kozaci c a Izmir Bozyaka E˘ gitim ve Arastirma Hastanesi, 1, Ic Hastaliklari klinigi, Romatoloji Bolumu, 35380 Izmir, Turkey b Izmir Tepecik Training and Research Hospital, Department of Internal Medicine, Izmir, Turkey c Adnan Menderes University School of Medicine, Department of Biochemistry, Aydin, Turkey ∗ Corresponding
author. E-mail address: [email protected] (I. Sari). 9 July 2009 doi:10.1016/j.jbspin.2009.07.005
Drug rash with eosinophilia and systemic symptoms syndrome induced by sulfasalazine Keywords: Drug reactions Sulfasalazine Eosinophilia Acute renal failure Acute hepatitis
A 68 year-old woman who had bilateral knee pain for 3 years was prescribed sulfasalazine (1 g/d) and prednisolone (5 mg/d) with presumptive diagnosis of rheumatoid arthritis in another hospital.
87
At 6th week of treatment, she developed acute tonsillopharyngitis with fever and was given oral sulbactam-ampicillin (SAM). A rash appeared at 3rd day of ampicillin treatment spreading to whole body. Sulfasalazine and SAM were stopped but rash and fever persisted. Ceftriaxone was started 5 days later empirically. Fever persisted after 7 days of ceftriaxone treatment so that 20 mg methylprednisolone was started parenterally. However, the day after, she developed acute oliguric renal failure and referred to our emergency department. Physical examination revealed body temperature: 37 ◦ C, paleness, cryptic tonsillopharyngitis, extensive maculopapular eruptions, hypotension and tachycardia. Laboratory examination revealed high acute phase response, leukocytosis with eosinophilia and lymphocytosis, uremia, abnormal liver enzymes (Table 1). Peripheral smear confirmed eosinophilia with atypical lymphocytosis. Urinalysis revealed only pyuria. Viral serology for CMV, EBV, HIV, HBV and HCV were non-reactive. Parenteral hydration was introduced and methylprednisolone was continued as 20 mg/d. All laboratory abnormalities and rash improved within 3 weeks. Methyl-prednisolone was ceased at 4th week by gradual tapering. She was diagnosed as gonarthrosis due to lack of objective symmetrical polyarthritis, morning stiffness, anti-CCP and treated accordingly. DRESS syndrome is a rare but potentially fatal idiosyncratic systemic hypersensitivity syndrome most commonly associated with anticonvulsants and sulphonamides [1–3]. It is characterized with skin rash, eosinophilia and/or atypical lymphocytosis, and presence of at least one systemic abnormality as lymphadenomegaly, hepatitis, interstitial nephropathy, lung or myocardial involvement [4]. Features of available reports of sulfasalazine induced DRESS syndrome are listed in Table 2. Our patient had skin rash, eosinophilia, atypical lymphocytosis and hepatitis, fulfilling DRESS criteria. Although interstitial nephritis might be present, renal biopsy was not performed because of dramatic improvement with treatment. The pathophysiology of DRESS syndrome is still unclear. The accumulation of toxic drug metabolites is suggested. The responsible factor for toxic metabolite accumulation may be the genetic predisposition as it is more common among members of the same family, slow acetylators and in blacks [3]. Several viral infections are
Table 1 Results of laboratory investigations of our patient. Investigation
Result
Leukocytes (/mm3 ) Neutrophils (/mm3 ) Lymphocytes (/mm3 ) Eosinophils (/mm3 ) Basophils (/mm3 ) Thrombocytes (/mm3 ) CRP (mg/l)
48,400 2800 6900 24,200 2500 427,000 179
Normal value
Investigation
Result
4000–11,000 1900–8000 900–5200 <800 <200 150,000–400,000 <5
BUN (mg/dl) Creatinine (mg/dl) AST (U/l) ALT (U/l) ALP (U/l) GGT (U/l)
49.5 4.5 103 146 946 721
Normal value 8–22 0.7–1.4 5–42 5–45 90–260 5–85
CRP: C reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase; GGT: gamma glutamyl transpeptidase. Table 2 Reported cases of sulfasalazine induced drug rash with eosinophilia and systemic symptoms syndrome. YOP
Age/Sex
WBC (/mm3 )
Our case 2008 2006 2006 2006 2006 2005 2005 2001 1999
68/F 47/F 39/M 49/F 30/? 46/F 63/F 45/F 15/F 30/F
48,400 16,980 7800 29,100 ∼16,000 9000 18,300 NA ∼16,500 19,000
Eosinophils (/mm3 ) 24,200 1430 3800 2910 2170 1700 9300 12,000 901 1182
CRP (mg/l)
Antibiotics
Viruses
OI
IOS
Interval (weeks)
Reference
179 50 normal NR 82 95 329 53 NR 33
SAM none none none none NXA AMX none none none
none none HHV6 none EBV none HHV6 none none none
L, K L L L L L L L L L
RA SNA SNA RA SNA RA RA RA PSA PSA
6 8 4 4 4 5 8 2 2 5
Our case [7] [8] [9] [10] [1] [3] [11] [12] [13]
YOP: year of publication; WBC: white blood cell count; CRP: C reactive protein; OI: organ involvement; IOS: indication of sulfasalazine ; Interval: interval between sulfasalazine treatment and onset of DRESS syndrome; F: female; M: male; NA: not accessible; SAM: ampicillin-sulbactam; NXA: nalidixic acid; AMX: amoxicillin; HHV6: human herpes virus 6; L: liver; K: kidney; LN: lung; RA: rheumatoid arthritis; SNA: seronegative arthritis; PSA: psoriatic arthritis; NR: not reported.
88
Letters to the editor / Joint Bone Spine 77 (2010) 81–89
associated with DRESS syndrome [3,5,6]. Viruses may interfere with drug metabolism resulting in toxic metabolite accumulation or the infection itself may act as a triggering factor for DRESS syndrome e.g. via decreasing antioxidant protection by decreasing cysteine level as in HIV infection [3]. The prior history of acute tonsillopharyngitis nonresponsive to antibiotherapy was suggestive for the role of a viral infection in our patient. Furthermore, we suggest that an additional antibiotic use may have a potential triggering role in the development of DRESS syndrome. In two other reports of sulfasalazine induced DRESS syndrome there were infections treated with amoxicillin and nalidixic acid [1,3]. In both cases, rash developed 2–5 days after introduction of antibiotics as in our case. Similar to viral infections, it may be speculated that the metabolites of some antibiotics may interfere with sulfasalazine metabolism resulting in accumulation of toxic metabolites. Whether antibiotic use is a risk factor for DRESS syndrome associated with sulfasalazine or it is a coincidence could be identified by further reports considering this issue. We conclude that increased awareness of this syndrome is essential among sulfasalazine prescribers to decrease related morbidity and mortality. References [1] Bejia I, Ben Hammouda S, Riahi K, et al. DRESS syndrome induced by sulphasalazine in rheumatoid arthritis. Joint Bone Spine 2006;73:764–5. [2] Garnier A, El Marabet El H, Kwon T, et al. Acute renal failure in a 3-year-old child as part of the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome following hepatitis A. Pediatr Nephrol 2008;23:667–9. [3] Michel F, Navellou JC, Ferraud D, et al. DRESS syndrome in a patient on sulfasalazine for rheumatoid arthritis. Joint Bone Spine 2005;72:82–5. [4] Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg 1996;15:250–7. [5] Seishima M, Yamanaka S, Fujisawa T, et al. Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome. Br J Dermatol 2006;155:344–9. [6] Descamps V, Valance A, Edlinger C, et al. Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms. Arch Dermatol 2001;137:301–4. [7] de Aquino RT, Vergueiro CS, Magliari ME, et al. Sulfasalazine-induced DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms). Sao Paulo Med J 2008;126:225–6. [8] Condat B, Zanditenas D, Collot V, et al. A new cause of intra and extrahepatic cholangitis: the drug hypersensitivity syndrome or DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Gastroenterol Clin Biol 2006;30:142–6. [9] Teo L, Tan E. Sulphasalazine-induced DRESS. Singapore Med J 2006;47:237–9. [10] Bourguignon R, Piérrard-Franchimont C, Paquet P, et al. DRESS syndrome to sulfasalzine. Rev Med Liege 2006;61:643–8. [11] Descloux E, Argaud L, Dumortier J, et al. Favourable issue of a fulminant hepatitis associated with sulfasalazine DRESS syndrome without liver transplantation. Intensive Care Med 2005;31:1727–8. [12] Queyrel V, Catteau B, Michon-Pasturel U, et al. DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome after sulfasalazine and carmazepine: report of two cases. Rev Med Interne 2001;22:582–6. [13] Bouyssou-Gauthier ML, Bédane C, Boulinguez S, et al. Photosensitivity with sulfasalazopyridine hypersensitivity syndrome. Dermatology 1999;198:388–90.
Prolidase deficiency: A rare aetiology of arthritis Keywords: Genetic Prolidase deficiency Auto-immune disorder
We report an association between prolidase deficiency (PD) and an auto-immune disease. In 2003, a 25-year-old man, from Portugal, presented with a several month history of bilateral and symmetric synovitis affecting hands, elbows, and knees. He had no medical familial history, but presented a small size (1,64 m), a dysmorphic face with facial cicatricial lesions, and grey hair (Fig. 1A). In addition, he had from childhood clubbing of the fingers (Fig. 1B) related to a chronic lymphocytic bronchiolitis in an active smoker (12 packs-year). Further assessment discovered signs of vasculitis (necrotic digital lesions and diffuse axonal neuropathy), hepatosplenomegaly, and leg ulcer dermatitis (Fig. 1C). Blood studies showed high inflammatory markers (ESR at 54 mm/h and CRP at 34 mg/l), with signs of auto-immunity: positive rheumatoid factor (516 IU/ml), homogeneous anti-nuclear antibodies (1/640) without anti-DNA antibodies, low levels of C4 and CH50 (0.07 g/l and 61%, respectively) and a type II mixed cryoglobulinemia. Synovial fluid showed inflammation with 3500 WBC/mm3 without crystals. Hepatitis B and C virus, and HIV antibodies were negative. Urinary analysis showed a mixed glomerular and tubular proteinuria (0.15 g per 24 hours), whereas glomerular filtration rate was normal. X-rays revealed no bone erosion or space narrowing on hands (Fig. 1D) and osteopenia on thoracic vertebra (Fig. 1E). Based on this presentation, this patient presented a rhupus [1] since he met the American College of Rheumatology (ACR) criteria for both rheumatoid arthritis and lupus. To explore this clinical picture, HPLC analysis of urinary amino acids revealed an important excretion of iminodipeptides. This led to the diagnosis of PD [2]. Prolidase acts by cleaving dipeptides with a C-terminal proline or hydroxyproline. In PD, a large amount of the proline bound to iminopeptides is excreted in urine. While usually only hydroxyproline is excreted in the urine, this results in the depletion of the total body pool of proline. Since collagen contains ∼25% of proline, we investigated bone remodeling markers. CTX-I and osteocalcin levels were elevated at 1300
Gulistan Bahat a,∗ Hulya Gamze Celik b Fatih Tufan a Bulent Saka a a Department of Internal Medicine, Istanbul Medical School, Istanbul University, Capa 34390, Istanbul, Turkey b Institute of Cardiology, Istanbul University, Istanbul, Turkey ∗ Corresponding author. E-mail address: [email protected] (G. Bahat).
13 August 2009 doi:10.1016/j.jbspin.2009.08.003
Fig. 1. Main characteristic of prolidase deficiency (PD) in our patient. (A) Dysmorphic face with grey hair, facial cicatricial (arrow), kyphosis and leg ulcer dermatitis (C) are the main clinical manifestations of prolidase deficient. Some uncommon manifestations which presented in our patient: childhood clubbing of the fingers (B) and necrotic digital lesions (B insert). On x-rays, no bone erosion or reduction of space narrowing was observed (D), but osteopenia was observed on thoracic vertebra (E).
Ismail Sari a,∗ Ahmet Alacacioglu a Levent Kebapcilar a Ali Taylan b Oktay Bilgir a Yasar Yildiz a Arif Yuksel a Didem L. Kozaci c a Izmir Bozyaka E˘ gitim ve Arastirma Hastanesi, 1, Ic Hastaliklari klinigi, Romatoloji Bolumu, 35380 Izmir, Turkey b Izmir Tepecik Training and Research Hospital, Department of Internal Medicine, Izmir, Turkey c Adnan Menderes University School of Medicine, Department of Biochemistry, Aydin, Turkey ∗ Corresponding
author. E-mail address: [email protected] (I. Sari). 9 July 2009 doi:10.1016/j.jbspin.2009.07.005
Drug rash with eosinophilia and systemic symptoms syndrome induced by sulfasalazine Keywords: Drug reactions Sulfasalazine Eosinophilia Acute renal failure Acute hepatitis
A 68 year-old woman who had bilateral knee pain for 3 years was prescribed sulfasalazine (1 g/d) and prednisolone (5 mg/d) with presumptive diagnosis of rheumatoid arthritis in another hospital.
87
At 6th week of treatment, she developed acute tonsillopharyngitis with fever and was given oral sulbactam-ampicillin (SAM). A rash appeared at 3rd day of ampicillin treatment spreading to whole body. Sulfasalazine and SAM were stopped but rash and fever persisted. Ceftriaxone was started 5 days later empirically. Fever persisted after 7 days of ceftriaxone treatment so that 20 mg methylprednisolone was started parenterally. However, the day after, she developed acute oliguric renal failure and referred to our emergency department. Physical examination revealed body temperature: 37 ◦ C, paleness, cryptic tonsillopharyngitis, extensive maculopapular eruptions, hypotension and tachycardia. Laboratory examination revealed high acute phase response, leukocytosis with eosinophilia and lymphocytosis, uremia, abnormal liver enzymes (Table 1). Peripheral smear confirmed eosinophilia with atypical lymphocytosis. Urinalysis revealed only pyuria. Viral serology for CMV, EBV, HIV, HBV and HCV were non-reactive. Parenteral hydration was introduced and methylprednisolone was continued as 20 mg/d. All laboratory abnormalities and rash improved within 3 weeks. Methyl-prednisolone was ceased at 4th week by gradual tapering. She was diagnosed as gonarthrosis due to lack of objective symmetrical polyarthritis, morning stiffness, anti-CCP and treated accordingly. DRESS syndrome is a rare but potentially fatal idiosyncratic systemic hypersensitivity syndrome most commonly associated with anticonvulsants and sulphonamides [1–3]. It is characterized with skin rash, eosinophilia and/or atypical lymphocytosis, and presence of at least one systemic abnormality as lymphadenomegaly, hepatitis, interstitial nephropathy, lung or myocardial involvement [4]. Features of available reports of sulfasalazine induced DRESS syndrome are listed in Table 2. Our patient had skin rash, eosinophilia, atypical lymphocytosis and hepatitis, fulfilling DRESS criteria. Although interstitial nephritis might be present, renal biopsy was not performed because of dramatic improvement with treatment. The pathophysiology of DRESS syndrome is still unclear. The accumulation of toxic drug metabolites is suggested. The responsible factor for toxic metabolite accumulation may be the genetic predisposition as it is more common among members of the same family, slow acetylators and in blacks [3]. Several viral infections are
Table 1 Results of laboratory investigations of our patient. Investigation
Result
Leukocytes (/mm3 ) Neutrophils (/mm3 ) Lymphocytes (/mm3 ) Eosinophils (/mm3 ) Basophils (/mm3 ) Thrombocytes (/mm3 ) CRP (mg/l)
48,400 2800 6900 24,200 2500 427,000 179
Normal value
Investigation
Result
4000–11,000 1900–8000 900–5200 <800 <200 150,000–400,000 <5
BUN (mg/dl) Creatinine (mg/dl) AST (U/l) ALT (U/l) ALP (U/l) GGT (U/l)
49.5 4.5 103 146 946 721
Normal value 8–22 0.7–1.4 5–42 5–45 90–260 5–85
CRP: C reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ALP: alkaline phosphatase; GGT: gamma glutamyl transpeptidase. Table 2 Reported cases of sulfasalazine induced drug rash with eosinophilia and systemic symptoms syndrome. YOP
Age/Sex
WBC (/mm3 )
Our case 2008 2006 2006 2006 2006 2005 2005 2001 1999
68/F 47/F 39/M 49/F 30/? 46/F 63/F 45/F 15/F 30/F
48,400 16,980 7800 29,100 ∼16,000 9000 18,300 NA ∼16,500 19,000
Eosinophils (/mm3 ) 24,200 1430 3800 2910 2170 1700 9300 12,000 901 1182
CRP (mg/l)
Antibiotics
Viruses
OI
IOS
Interval (weeks)
Reference
179 50 normal NR 82 95 329 53 NR 33
SAM none none none none NXA AMX none none none
none none HHV6 none EBV none HHV6 none none none
L, K L L L L L L L L L
RA SNA SNA RA SNA RA RA RA PSA PSA
6 8 4 4 4 5 8 2 2 5
Our case [7] [8] [9] [10] [1] [3] [11] [12] [13]
YOP: year of publication; WBC: white blood cell count; CRP: C reactive protein; OI: organ involvement; IOS: indication of sulfasalazine ; Interval: interval between sulfasalazine treatment and onset of DRESS syndrome; F: female; M: male; NA: not accessible; SAM: ampicillin-sulbactam; NXA: nalidixic acid; AMX: amoxicillin; HHV6: human herpes virus 6; L: liver; K: kidney; LN: lung; RA: rheumatoid arthritis; SNA: seronegative arthritis; PSA: psoriatic arthritis; NR: not reported.
88
Letters to the editor / Joint Bone Spine 77 (2010) 81–89
associated with DRESS syndrome [3,5,6]. Viruses may interfere with drug metabolism resulting in toxic metabolite accumulation or the infection itself may act as a triggering factor for DRESS syndrome e.g. via decreasing antioxidant protection by decreasing cysteine level as in HIV infection [3]. The prior history of acute tonsillopharyngitis nonresponsive to antibiotherapy was suggestive for the role of a viral infection in our patient. Furthermore, we suggest that an additional antibiotic use may have a potential triggering role in the development of DRESS syndrome. In two other reports of sulfasalazine induced DRESS syndrome there were infections treated with amoxicillin and nalidixic acid [1,3]. In both cases, rash developed 2–5 days after introduction of antibiotics as in our case. Similar to viral infections, it may be speculated that the metabolites of some antibiotics may interfere with sulfasalazine metabolism resulting in accumulation of toxic metabolites. Whether antibiotic use is a risk factor for DRESS syndrome associated with sulfasalazine or it is a coincidence could be identified by further reports considering this issue. We conclude that increased awareness of this syndrome is essential among sulfasalazine prescribers to decrease related morbidity and mortality. References [1] Bejia I, Ben Hammouda S, Riahi K, et al. DRESS syndrome induced by sulphasalazine in rheumatoid arthritis. Joint Bone Spine 2006;73:764–5. [2] Garnier A, El Marabet El H, Kwon T, et al. Acute renal failure in a 3-year-old child as part of the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome following hepatitis A. Pediatr Nephrol 2008;23:667–9. [3] Michel F, Navellou JC, Ferraud D, et al. DRESS syndrome in a patient on sulfasalazine for rheumatoid arthritis. Joint Bone Spine 2005;72:82–5. [4] Bocquet H, Bagot M, Roujeau JC. Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS). Semin Cutan Med Surg 1996;15:250–7. [5] Seishima M, Yamanaka S, Fujisawa T, et al. Reactivation of human herpesvirus (HHV) family members other than HHV-6 in drug-induced hypersensitivity syndrome. Br J Dermatol 2006;155:344–9. [6] Descamps V, Valance A, Edlinger C, et al. Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms. Arch Dermatol 2001;137:301–4. [7] de Aquino RT, Vergueiro CS, Magliari ME, et al. Sulfasalazine-induced DRESS syndrome (Drug Rash with Eosinophilia and Systemic Symptoms). Sao Paulo Med J 2008;126:225–6. [8] Condat B, Zanditenas D, Collot V, et al. A new cause of intra and extrahepatic cholangitis: the drug hypersensitivity syndrome or DRESS (Drug Rash with Eosinophilia and Systemic Symptoms). Gastroenterol Clin Biol 2006;30:142–6. [9] Teo L, Tan E. Sulphasalazine-induced DRESS. Singapore Med J 2006;47:237–9. [10] Bourguignon R, Piérrard-Franchimont C, Paquet P, et al. DRESS syndrome to sulfasalzine. Rev Med Liege 2006;61:643–8. [11] Descloux E, Argaud L, Dumortier J, et al. Favourable issue of a fulminant hepatitis associated with sulfasalazine DRESS syndrome without liver transplantation. Intensive Care Med 2005;31:1727–8. [12] Queyrel V, Catteau B, Michon-Pasturel U, et al. DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome after sulfasalazine and carmazepine: report of two cases. Rev Med Interne 2001;22:582–6. [13] Bouyssou-Gauthier ML, Bédane C, Boulinguez S, et al. Photosensitivity with sulfasalazopyridine hypersensitivity syndrome. Dermatology 1999;198:388–90.
Prolidase deficiency: A rare aetiology of arthritis Keywords: Genetic Prolidase deficiency Auto-immune disorder
We report an association between prolidase deficiency (PD) and an auto-immune disease. In 2003, a 25-year-old man, from Portugal, presented with a several month history of bilateral and symmetric synovitis affecting hands, elbows, and knees. He had no medical familial history, but presented a small size (1,64 m), a dysmorphic face with facial cicatricial lesions, and grey hair (Fig. 1A). In addition, he had from childhood clubbing of the fingers (Fig. 1B) related to a chronic lymphocytic bronchiolitis in an active smoker (12 packs-year). Further assessment discovered signs of vasculitis (necrotic digital lesions and diffuse axonal neuropathy), hepatosplenomegaly, and leg ulcer dermatitis (Fig. 1C). Blood studies showed high inflammatory markers (ESR at 54 mm/h and CRP at 34 mg/l), with signs of auto-immunity: positive rheumatoid factor (516 IU/ml), homogeneous anti-nuclear antibodies (1/640) without anti-DNA antibodies, low levels of C4 and CH50 (0.07 g/l and 61%, respectively) and a type II mixed cryoglobulinemia. Synovial fluid showed inflammation with 3500 WBC/mm3 without crystals. Hepatitis B and C virus, and HIV antibodies were negative. Urinary analysis showed a mixed glomerular and tubular proteinuria (0.15 g per 24 hours), whereas glomerular filtration rate was normal. X-rays revealed no bone erosion or space narrowing on hands (Fig. 1D) and osteopenia on thoracic vertebra (Fig. 1E). Based on this presentation, this patient presented a rhupus [1] since he met the American College of Rheumatology (ACR) criteria for both rheumatoid arthritis and lupus. To explore this clinical picture, HPLC analysis of urinary amino acids revealed an important excretion of iminodipeptides. This led to the diagnosis of PD [2]. Prolidase acts by cleaving dipeptides with a C-terminal proline or hydroxyproline. In PD, a large amount of the proline bound to iminopeptides is excreted in urine. While usually only hydroxyproline is excreted in the urine, this results in the depletion of the total body pool of proline. Since collagen contains ∼25% of proline, we investigated bone remodeling markers. CTX-I and osteocalcin levels were elevated at 1300
Gulistan Bahat a,∗ Hulya Gamze Celik b Fatih Tufan a Bulent Saka a a Department of Internal Medicine, Istanbul Medical School, Istanbul University, Capa 34390, Istanbul, Turkey b Institute of Cardiology, Istanbul University, Istanbul, Turkey ∗ Corresponding author. E-mail address: [email protected] (G. Bahat).
13 August 2009 doi:10.1016/j.jbspin.2009.08.003
Fig. 1. Main characteristic of prolidase deficiency (PD) in our patient. (A) Dysmorphic face with grey hair, facial cicatricial (arrow), kyphosis and leg ulcer dermatitis (C) are the main clinical manifestations of prolidase deficient. Some uncommon manifestations which presented in our patient: childhood clubbing of the fingers (B) and necrotic digital lesions (B insert). On x-rays, no bone erosion or reduction of space narrowing was observed (D), but osteopenia was observed on thoracic vertebra (E).