Primary systemic amyloidosis initially presenting with digestive symptoms: a case report and review of the literature
© Lin et al. 2015
Received: 10 July 2015
Accepted: 28 August 2015
Published: 21 September 2015
Primary systemic amyloidosis (PSA) is one of systemic amyloidosis, characterized by clonal plasma cell disorder. The disease is rare and with high fatality. Signs and symptoms of PSA are various and complex, which depend on the organs involved. Here we report a case in which the patient initially suffered from gastrointestinal symptoms. Gradually periorbital purpura, skin fragility, and subsequent petechiae, ecchymoses and sclerosis of the distal limbs, appeared. Biopsy of his palmar skin showed scleroderma-like changes. However, histopathology of the petechiae lesion on forehead with Crystal Violet Staining prompted deposition of amyloid; gastric mucosal biopsy with Congo Red staining was also positive, which made clear the diagnosis of PSA. Bone marrow biopsy and serum immunofixation electrophoresis (IFE) revealed plasmacytosis and M proteinemia. Other examinations were performed to assess the function of organs. PSA was challenging due to the initial atypical clinical presentation and absence of biopsy with special staining. The case demonstrates that PSA should be considered in patients with multisystemic symptoms and biopsy with Congo Red staining should be performed to exclusively diagnose amyloidosis.
KeywordsPrimary systemic amyloidosis Gastrointestinal symptoms Biopsy Congo Red staining Plasmacytosis M proteinemia
Primary systemic amyloidosis (PSA), also called Lubarsch-Pick disease, is a rare, complex and protean disease. Currently, it is a mortal disease without any effective therapy, and its median survival time is approximatedly 13 months . In the US, the incidence of PSA is estimated to be approximately 1275 to 3200 new cases per year . Here we report a case of PSA initially presenting with gastrointestinal symptoms. However, it had been misdiagnosed of scleroderma and recurrent chronic gastritis.
PSA is a clonal plasma cell disorder, including the production, aggregation, polymerization, fibril formation and finally extracellular deposition in various organs of the precursor protein, ultimately leading to organ dysfunction and death . Symptoms and signs of it are various and complex, which depend on the organs involved. In the early state, patients may present some non-specific clinical symptoms, such fatigue, weight loss, paresthesias and syncopal attacks, just as the patient in this case. Guadually, intracutaneous hemorrhage manifests in the form of petechiae, purpura and ecchymoses due to infiltration of blood vessel walls by amyloid deposits, which are the most common skin lesions. At the same time, symptoms of the affected organs can appear, manifesting multisystem symptoms. In some cases, skin lesions can be atypical, such as multiple papules  instead of petechiae and ecchymoses on head and face. In other words, insufficient understanding of the rash is easy to lead to misdiagnosis and delay of treatments.
Clinical classification of amyloidosis
Clinical classification of amyloidosis including
Primary systemic amyloidosis(AL> > AH amyloid protein)
Plasma cell dyscrasias (more common)
Secondary systemic amyloidosis (reactive;AA amyloid protein)
Chronic inflammation (e.g.rheumatoid arthritis)
Chronic infection (e.g.tuberculosis)
Heredofamilial amyloidosis (various amyloid proteins)
Familial amyloidotic polyneuropathy
Familial Mediterranean fever
Primary:macular, lichen, biphasic, dyschromic, nodular
Secondary:within skin tumors
Medullary carcinoma of the thyroid, insulinoma, type 2 diabetes
Alzheimer 's disease
In summary, clinical manifestations of PSA are diverse and nonspecific. It should be considered in patients with skin lesion such as petechiae, purpura and ecchymoses, especially accompanying with multisystemic symptoms. Biopsy of lesion with Congo Red staining is of diagnostic significance.
Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images.
This work was supported by the Department of Dermatopathology of the Second Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
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- Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol. 1995;32:45–59.PubMedGoogle Scholar
- Falk RH, Comenzo RL, Skinner M. The systemic amyloidoses. N Engl J Med. 1997;337:898–909.View ArticlePubMedGoogle Scholar
- Black MM, Upjohn E, Albert S. Amyloidosis. In: Jean L, Bolognia, Joseph L, Jorizzo, Ronald P, Rapini. Dermatology. Mosby 2008: 623–631.Google Scholar
- Kumar S, Sengupta RS, Kakkar N, Sharma A, Singh S, Varma S. Skin involvement in primary systemic amyloidosis [J]. Mediterr J Hematol Infect Dis. 2013;5(1):e2013005.PubMed CentralView ArticlePubMedGoogle Scholar
- Lachmann HJ, Booth DR, Booth SE, Bybee A, Gilbertson JA, Gillmore JD, et al. Misdiagnosis of hereditary amyloidosis as AL (primary) amyloidosis [J]. New England Journal of Medicine. 2002;346(23):1786–91.View ArticlePubMedGoogle Scholar
- Hayman SR, Lacy MQ, Kyle RA, Gertz MA. Primary systemic amyloidosis: a cause of malabsorption syndrome [J]. The American journal of medicine. 2001;111(7):535–40.View ArticlePubMedGoogle Scholar
- Nuhoglu I, Civan N, Ucuncu O, Kocak M, Coskun H, Turgutalp H. Amyloid goiter as an unusual presentation of primary systemic amyloidosis: A case report. 2014.Google Scholar
- Obici L, Perfetti V, Palladini G, Moratti R, Merlini G. Clinical aspects of systemic amyloid diseases [J]. Biochimica et Biophysica Acta (BBA)-Proteins and. Proteomics. 2005;1753(1):11–22.Google Scholar
- Menke DM, Kyle RA, Fleming CR, Wolfe JT 3rd, Kurtin PJ, Oldenburg WA. Symptomatic gastric amyloidosis in patients with primary systemic amyloidosis[C]//Mayo Clinic Proceedings. Elsevier. 1993;68(8):763–7.Google Scholar
- Sattianayagam PT, Hawkins PN, Gillmore JD. Systemic amyloidosis and the gastrointestinal tract [J]. Nature Reviews Gastroenterology and Hepatology. 2009;6(10):608–17.View ArticlePubMedGoogle Scholar
- Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis [J]. The American journal of gastroenterology. 2008;103(3):776–87.View ArticlePubMedGoogle Scholar
- Yamada M, Hatakeyama S, Tsukagoshi H. Gastrointestinal amyloid deposition in AL (primary or myeloma-associated) and AA (secondary) amyloidosis: diagnostic value of gastric biopsy [J]. Human pathology. 1985;16(12):1206–11.View ArticlePubMedGoogle Scholar
- Tada S, Iida M, Iwashita A, Matsui T, Fuchigami T, Yamamoto T, et al. Endoscopic and biopsy findings of the upper digestive tract in patients with amyloidosis [J]. Gastrointestinal endoscopy. 1990;36(1):10–4. http://www.sciencedirect.com/science/article/pii/S0016510790709133.
- Tada S, Iida M, Yao T, Kawakubo K, Yao T, Okada M, et al. Endoscopic features in amyloidosis of the small intestine: clinical and morphologic differences between chemical types of amyloid protein [J]. Gastrointestinal endoscopy. 1994;40(1):45–50.View ArticlePubMedGoogle Scholar
- James DG, Zuckerman GR, Sayuk GS, Wang HL, Prakash C. Clinical recognition of Al type amyloidosis of the luminal gastrointestinal tract [J]. Clinical Gastroenterology and Hepatology. 2007;5(5):582–8.View ArticlePubMedGoogle Scholar
- Gertz MA. Secondary amyloidosis. J Int Med. 1992;232:517–8.View ArticleGoogle Scholar
- Zhang Q, Ji Y, He T, Wang J. Ultrasound-guided percutaneous renal biopsy-induced accessory renal artery bleeding in an amyloidosis patient [J]. Diagnostic pathology. 2012;7(1):176.PubMed CentralView ArticlePubMedGoogle Scholar