|Year : 2013 | Volume
| Issue : 2 | Page : 138-141
Primary systemic amyloidosis
Haritha Samanthula, Dinesh P Deshpande, Videesha Parvathaneni
Department of Dermatology, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Chinoutpalli, Krishna, Andhra Pradesh, India
|Date of Web Publication||21-May-2013|
Department of Dermatology, Dr. Pinnamaneni Siddhartha Institute of Medical Sciences and Research Foundation, Chinnavutapalli, Vijayawada, Andhra Pradesh
Source of Support: None, Conflict of Interest: None
A 54-year-old male presented with nodular lesions over the tongue and progressive discoloration around the eyes of 1-year duration. Patient had history of dysphagia, dyspnea, dysphonia, progressive weakness, and tingling and numbness of the extremities. Clinical examination revealed macroglossia, periorbital purpura, carpal tunnel syndrome, and waxy nodules around the eyes and lateral borders of the tongue. A diagnosis of primary systemic amyloidosis was made. Biopsy showed eosinophilic deposits in the papillary dermis on hematoxylin and eosin (H and E) staining. Congo red stained sections showed areas of apple green birefringence under polarized light microscopy, confirming the diagnosis of amyloidosis.
Keywords: Macroglossia, periorbital purpura, primary systemic amyloidosis
|How to cite this article:|
Samanthula H, Deshpande DP, Parvathaneni V. Primary systemic amyloidosis. J NTR Univ Health Sci 2013;2:138-41
| Introduction|| |
Amyloidosis is a generic term, originally coined by Rudolf Virchow in 1854, which denotes extracellular deposition of a proteinaceous substance, amyloid composed of one of a family of biochemically unrelated proteins. 
Amyloidosis can be classified as systemic and cutaneous amyloidosis. Systemic amyloidosis is classified into primary and secondary. 
Primary systemic amyloidosis is a rare disorder. Wilks in 1856, was the first to describe primary systemic amyloidosis.  Primary systemic amyloidosis may be idiopathic or myeloma associated. Primary and myeloma-associated systemic amyloidosis typically involve the tongue, heart, gastrointestinal tract, skeletal and smooth muscle, carpal ligaments, nerves, and skin.  We report a case of primary systemic amyloidosis with classical cutaneous findings.
| Case Report|| |
A 54-year-old male presented with enlarged tongue and discoloration in the periorbital and perioral region of 1-year duration. The patient initially developed multiple swellings over the sides of the tongue, which gradually increased in size and number. The patient had observed enlargement of the tongue for the past 1 year. He also had associated dysphagia and hoarseness of the voice. There was discoloration around the eyes and perioral area, which gradually increased in intensity leading to black eyes for the last 1 year. Patient gave a history of tingling and numbness of the right hand and generalized weakness for the past 6 months. There were no other systemic complaints or any chronic illnesses in the past.
On examination, vital parameters were normal. Pallor and pedal edema were present. Multiple smooth shiny waxy nodules about 0.5 cm in size were seen around the eyes, nose, and mouth. Purpuric patches (pinch purpura) were present around the eyes and mouth [Figure 1]. Macroglossia with tooth indentation was present and red, waxy nodules along the lateral borders of the tongue were seen [Figure 2] and [Figure 3]. Subconjunctival hemorrhage in the left eye was present. Nails showed crumbling and longitudinal ridges [Figure 4]. Systemic examination was found to be normal. Carpal tunnel syndrome was present with positive Tinel's sign and Phalen's test.
Routine hematological investigations revealed Hb: 9.7 gm%. Ultrasonography for abdomen was normal. Urine for Bence-Jones proteins was negative. Serum protein elctrophoresis was normal.Chest X Ray, ECG and Echo cardiogram were normal.
Biopsy from the tongue showed parakeratinized stratified squamous epithelium. H and E stain showed noninflammatory infiltrate with eosinophilic masses in the papillary dermis [Figure 5]. Sections stained with Congo red showed brick-red color of amyloid under ordinary light and areas of apple-green birefringence under polarized light microscopy [Figure 6] and [Figure 7].
|Figure 5: Hematoxylin and eosin stain showing eosinophilic masses in the papillary dermis|
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|Figure 7: Apple-green birefringence under polarized light with Congo red stain|
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| Discussion|| |
Amyloidosis is caused by extracellular deposition of insoluble abnormal fibril derived from the aggregation of misfolded plasma protein. More than 20 unrelated proteins are known to form human amyloid fibrils in vivo.  These proteins are arranged in cross-β-pleated sheet configuration that makes it highly insoluble and resistant to proteolytic digestion. In primary systemic and myeloma-associated amyloidosis, the fibrils are composed of "protein AL", commonly λ class with low molecular weight and of lower isoelectric point. 
Amyloidosis develops in about 15% of patients with myelomatosis. Majority of patients with amyloid light-chain (AL) amyloidosis do not have obvious β cell/plasma cell neoplasm (idiopathic). In multiple myeloma associated AL amyloidosis, precursor light chains of immunoglobulin (Bence–Jones protein) are produced in large quantity by malignant plasma cell clone and can be detected in serum or urine by electrophoresis.
Although different types of amyloidosis are associated with distinct clinical pictures, all amyloids have certain common features:
- Amorphous eosinophilic appearance on light microscopy in H and E staining.
- Bright-green fluorescence observed under polarized light after Congo red staining.
- Beta-pleated structure on X-ray crystallography. 
Primary systemic amyloidosis (AL) is known for highly varied clinical manifestations.
Cutaneous involvement is seen in 40% patients with AL amyloidosis. Cutaneous manifestations depend on the site of amyloid deposited. Amyloid deposition in superficial dermis produces shiny waxy translucent papules, and common sites of predilection are eyelids, retroauricular areas, neck, and axillae. Amyloid deposits in the deep reticular dermis and subcutis produce nodules and tumefactions. Amyloid infiltration of blood vessel walls produces capillary wall fragility leading to purpura clinically. Periorbital area is the most common site of purpura and may be demonstrable by pinching the skin. 
Saoji et al., have reported three cases of primary systemic amyloidosis of which one case was associated with multiple myeloma. Purpuric lesions were the only presenting symptom of the patient with myeloma, and only on investigations multiple myeloma was detected. The other two patients without myeloma presented with typical waxy lesions on the face.  Our case also presented with typical purpuric patches and waxy nodules around the eyes, nose, and mouth. Investigations such as serum protein electrophoresis and urine analysis for Bence–Jones proteins were negative revealing that there was no associated myeloma.
Diffuse infiltration of scalp skin results in the enlargement of skin which gets thrown into longitudinal folds resembling cutis verticis gyrata. Infiltration of nail matrix by amyloid may produce ridging, splitting, and brittleness of nail plate. Diffuse infiltration of large area of skin may simulate scleroderma. Amyloid deposition in tongue leads to macroglossia (occurs in 10% cases). Tongue is diffusely enlarged, firm and fissured with hemorrhagic papules, plaques, nodules and bullae. There may be permanent tooth indentation on the lateral borders of the tongue.  Saoji et al., have reported macroglossia in all the three cases.  In our case the tongue was grossly enlarged with tooth indentations and waxy nodules along the lateral borders.
Hepatomegaly occurs in 50% of patients, Congestive cardiac failure, and nephrotic syndrome in 30% of patients, and splenomegaly occurs in about 10%. Renal involvement manifests as proteinuria and consequently hypoalbuminemia and edema. Vaz et al., have reported a case of 45-year-old male with nephrotic syndrome associated with primary systemic amyloidosis.  Cardiac involvement may lead to congestive cardiac failure resulting in dyspnea, elevated jugular venous pressure, hepatomegaly, and bilateral pedal edema.  However, in our case, renal and cardiac evaluation was found to be normal.
Carpal tunnel syndrome is seen in up to 25% of patients of primary systemic amyloidosis, which is one of the positive findings in our case.
The diagnosis of primary systemic amyloidosis can be confirmed by demonstration of amyloid in skin biopsy. In 80-90% of patients with primary systemic amyloidosis, amyloid can be demonstrated in rectal mucosal biopsies or in abdominal subcutaneous fat aspirates. Gingival and tongue biopsies may also be used to demonstrate the presence of amyloid.  According to Barbhuiya et al., aspirate of fat from abdominal subcutaneous tissue is easy to obtain and very reliable (88% positivity) for systemic amyloidosis. 
Prognosis in AL amyloidosis is poor and major causes of death are cardiac and renal failure. 
Various therapies such as melphalan, prednisolone, colchicine have been advocated for primary systemic amyloidosis of which some appear promising, but cost could be a limiting factor.
| References|| |
|1.||Breathnach SM. Metabolic and nutritional disorders. In: Burns T, Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of Dermatology. 8 th ed. Oxford: Wiley-Blackwell; 2010. p. 57.36-57.51. |
|2.||James WD, Berger TG, Elston DM. Errors in metabolism. In: Andrews' Diseases of the Skin: Clinical Dermatology. 10 th ed. Philadelphia: Saunders Elsevier: 2006. p. 519-22. |
|3.||Kyle RA, Greipp PR. Amyloidosis (AL). Clinical and laboratory features in 229 cases. Mayo Clin Proc 1983;58:665-83. |
|4.||Pepys MB. Amyloidosis. Annu Rev Med 2006;57:223-41. |
|5.||Buxbaum J. The amyloidosis. Mt Sinai J Med 1996;63:16-23. |
|6.||Gertz MA, Lacy MQ, Dispenzieri A. Amyloidosis recognition, confirmation, prognosis, therapy. Mayo Clin Proc 1999;74:490-4. |
|7.||Baethge BA, Jacobson DR. Amyloidosis, overview. Available from: http://emedicine.medscape.com/article/335414-overview [Last accessed on 2009 Jan 24]. |
|8.||Saoji V, Chaudhari S, Gohokar D. Primary systemic amyloidosis: Three different presentations. Indian J Dermatol Venereol Leprol 2009;75:394-7. |
|9.||Vaz BA, Ashwani V, Malkani RH. Primary systemic amyloidosis. Indian J Dermatol Venereol Leprol 1993;59:93-6. |
|10.||Martin MB. Amyloidosis. In: Bolognia JL, Joseph LJ, Rapini RP, editors. Dermatology. 2 nd ed. St. Louis: Mosby Elsevier; 2008. p. 623-31. |
|11.||Barbhuiya JN, Guha PK, Dutta BN. Primary systemic amyloidosis presenting as periorbital pigmentation. Indian J Dermatol Venereol Leprol 1994;60:34-6. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]