International Journal of Rheumatic Diseases 2011
LETTER TO THE EDITOR
A case of primary systemic amyloidosis Dear Sir, Here we present a 48-year-old male patient with arthralgia and back pain of 2 years duration. He reported hypertension and renal failure on his past medical history from 1 month ago. He also mentioned a history of bilateral paresthesia of his hands over the past year. He was given losartan, diltiazem, erythropoietin, carnitin and calciteriol for renal failure and hypertension. On physical examinations, his blood pressure was 105/60 mmHg. Small translucent papules were noted on his auricles, nostrils and around his eyes (Fig. 1). No lymphadenopathy was found. Heart and lung examinations were normal. No organomegaly was discovered. Tenderness and limitation of motion was found in all joints of the upper and lower extremities, neck and lumbar region. Tenderness of the sacroiliacs and swelling of the knee joints and wrists were also found. He had Heberden and Bouchard nodes on his distal and proximal interphalangial joints of the hands, respectively. Laboratory tests showed the following results: white blood cell count (WBC), 10 500/mm3; hemaglobin, 11.7/mm3; platelet count 264/mm3; blood urea nitrogen 37 mg/dL (normal 10–40); creatinin, 3.3 mg/dL (up to 1.5); fasting blood sugar, 99 mg/dL (70–110); sodium,142 mEq/dL (130–146); potassium, 4.5 mEq/ dL (3.5–5.3); calcium, 9.4 mg/dL (8.5–10.5); posphorus, 4.7 mg/dL (2.5–5.0); erythrocyte sedimentation rate, 20 mL/h; C-reactive protein, negative; rheumatoid factor, negative; standard agglutination test for brucellosis (Wright) and 2-mercaptoethanol (2ME) titers, negative; HLAB27, negative; prostate specific antigen, 0.6 ng/mL (0–4); liver and thyroid function tests, normal; uric acid, 9.2 mg/dL (3.9–8); urine analysis, protein 3+ and 24-h urine collection, 4 g. Urine protein electrophoresis revealed light chain proteinuria (32.3 mg/dL). Joint aspiration fluid analysis showed the following: WBC, 600 cells/mm (differential: polymorphonuclear cells, 35% and lymphocytes, 65%); and red blood cell count, 500 cells/mm. Under polarized microscope no
Figure 1 Translucent papules of the skin.
crystals were seen. Then bone marrow aspiration was performed and showed 70% cellularity with diffuse plasma cell infiltration, some with atypical features and some with bilobular nuclei. Abdominal and pelvic ultrasonography revealed that the left kidney was smaller than normal (35 · 88 mm) with reduced cortical thickness and corticomedullary echo enhancement. A skin biopsy of one of the papules was performed. It showed orthokeratotic hyperkeratosis, focal thinning of the epidermis and amorphic acidophilic material in superficial and deep dermis (Fig. 2). Echocardiography was normal. Chest X-ray was normal and X-rays of the cervical and lumbar regions, knees and hands showed signs of osteoarthritis. The patient was diagnosed as having primary systemic amyloidosis that is a rare disease with an incidence of < 1/100 000 in the UK. It is a plasma-cell dyscrasia of unknown cause. Immunoglobulin light chains, or fragments of light chains, produced by plasma-cell clones form extracellular amyloid fibrils.1 Clearly, massive deposits are structurally disruptive and incompatible with normal function, while even small deposits strategically located, for example in the glomeuli, the heart or the nerves, can be destructive simply as space-occupying lesions. There is rarely any significant histological or systemic evidence of an inflammatory reaction to amyloid deposits, nor obvious signs of parenchymal cell death, suggesting that one pathoge-
ª 2011 The Authors International Journal of Rheumatic Diseases ª 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd
Letter to the Editor
Figure 2 Deposits of amorphous material in papillary dermis on Congo red stain.
netic pathway may just be the physical presence of inert material.2 Amyloid deposition can occur in any organ in the body, causing features such as congestive cardiac failure, renal failure and hepatosplenomegaly, as well as skin lesions.1 The presenting features are often varied and nonspecific, such as fatigue, weight loss, paresthesias, dyspnea and syncopal attacks.3 Our patient presented with bilateral hand paresthesia which was diagnosed as carpal tunnel syndrome on nerve conduction velocity (NCV), which led to surgery. Renal involvement manifests as proteinuria and consequently hypoalbuminemia and edema.3 Cardiac involvement may eventually lead to congestive heart failure. Autonomic and sensory neuropathies are common. Hepatomegaly due to amyloid infiltration is seen in approximately 50% of patients.3 Systemic amyloidosis has well-recognized dermatological signs that may be the presenting features of the disease. Purpura, petechiae and ecchymoses occur commonly in the skin and mucous membranes. They are due to intracutaneous hemorrhage, the result of amyloid infiltrating and weakening blood-vessel walls. Direct dermal infiltration can produce subcutaneous nodules and plaques. Classically described as smooth, waxy, yellowish lesions, these are uncommon and more often appear hemorrhagic.1 In our patient translucent papules on the face were biopsied and on Congo red staining, amyloid deposition in the papillary dermis was confirmed. They are generally
2
found on flexor surfaces, the face and the buccal mucosa. Macroglossia and alopecia may develop. Nail dystrophy is not unusual in systemic amyloidosis. Neuropathic skin changes may follow the infiltration of peripheral nerves with amyloidosis. Rarely, bullae may form on the skin or mucous membranes.1 Carpal tunnel syndrome, often bilateral, may be caused by amyloid deposits in the wrist compressing the median nerve and may occur years before the full clinical presentation of the disease. Amyloid infiltration of the skeletal muscle, typically involving the tendons and capsular structures of the shoulders, may result in pseudohypertrophy (shoulder pad sign). Amyloid deposits in bone may appear as cystic lucencies on radiographs and may result in pathologic fractures.4 Without therapy, the prognosis for primary systemic amyloidosis is poor: median survival is approximately 13 months. Two major trials have shown that treatment with a combination of melphalan and prednisolone is superior to no therapy or to therapy with colchicine alone, but median survival intervals were still short.3 Our patient presented with bilateral carpal tunnel syndrome, hypertension, nephrotic syndrome and dermal waxy papules of the face. Pathologic examination of these waxy papules led eventually to the diagnosis. Our patient was referred to an oncologist and received the same therapies. Zahra MIRFEIZI,1 Mohammad R. HATEF,1 Kamila HASHEMZADEH,1 Sarah HASHEMZADEH2 and Naser TAYEBI1 1
Mashhad University of Medical Sciences, Imam Reza Hospital, Mashhad, Iran; and 2 Vasei Hospital of Sabzevar, Sabzevar, Iran Correspondence: S. Hashemzadeh, email:
[email protected]
REFERENCES 1 Silverstein SR, Bchir MA (2005) Primary systemic amyloidosis and the dermatologist: where classic skin lesions may provide the clue for early diagnosis. Dermatol Online J 11, 5 2 Pepys MB (2006) Pathogenesis diagnosis and treatment of systemic amyloidosis. Annu Rev Med 57, 223–41. 3 Black MM, Upjohn E, Albert S (2008) Amyloidosis. In: Bolognia JL, Jorizzo JL, Rapini RP (eds) Dermatology, 2nd edn, pp 628–9. Mosby Elsevier, St. Louis. 4 Sarraf P, Kay J (2008) The amyloidosis. In: Klipple JH, Stone JH, Crofford LJ, White PH (eds) Primer on the Rheumatic Diseases, 13th edn, pp 533–42. Springer, New York.
International Journal of Rheumatic Diseases 2011
