MEDITERRANEANJOURNALOF HEMATOLOGYAND INFECTIOUS DISEASES www.mjhid.org ISSN2035-3006 CaseReport Skin Involvement in Primary Systemic Amyloidosis SusheelKumar1,RimiSomSengupta1,NanditaKakkar2,AmanSharma1,SurjitSingh1andSubhashVarma1 1DepartmentofInternalMedicine,PostgraduateInstituteofMedicalEducationandResearch,Chandigarh,India 2DepartmentofHistopathology,PostgraduateInstituteofMedicalEducationandResearch,Chandigarh,India Correspondence to: Susheel Kumar M.D, Assistant Professor of Internal Medicine, Department of Internal Medicine,PostgraduateInstituteofMedicalEducationandResearch,Chandigarh,India.Tel:91-9779178384 Fax:91-172-2744401.E-Mail:[email protected] Competinginterests:Theauthorshavedeclaredthatnocompetinginterestsexist. Published:January2,2013 Received:October3,2012 Accepted:November23,2012 Citation:MediterrJHematolInfectDis2013,5(1):e2013005,DOI:10.4084/MJHID.2013.005 Thisarticleisavailablefrom:http://www.mjhid.org/article/view/10807 This is an Open Access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/2.0),which permits unrestricted use, distribution, and reproduction in any medium,providedtheoriginalworkisproperlycited. Abstract. Primary systemic amyloidosis is a rare disease. It primarily involves kidney, heart, peripheral nerves and liver. Intracutaneous hemorrhage manifesting in the form of petechiae, purpura and ecchymoses due to infiltration of blood vessel walls by amyloid deposits are the most common skin lesions. We report a case of primary systemic amyloidosis with multiple, non-itchy, papular lesions in lower eyelids and lower chest wall bilaterally. Diagnosis was confirmed in this case by biopsy of skin lesions using congo red staining. Papular eruptions as seen in index patient arerelativelyuncommon formof skin manifestations. Introduction.Amyloidosis is a disease caused by amyloidosis (AL amyloidosis) may be idiopathic or extracellular deposition of insoluble polymeric protein myeloma-associated. It is the amyloidosis composedof fibrilsintissues andorgans.1-3 Thisdiseaseis classified immunoglobulin light chains. It involves kidney, heart, as localized or systemic amyloidosis depending on liver, peripheral nerves, autonomic nervous systemand whether amyloid deposition is localized to one organ sometimes lungs.1-8 Skin involvement may be seen in system or multiple organs. Amyloid is deposited in AL amyloidosis.Cutaneous manifestation depends previouslyapparentlynormal skin,with noevidence of upon the site of amyloid deposition.2Skin involvement deposits in any of internal organs in primary localized other than those related to intracutaneoushaemorrhage cutaneous amyloidosis (PLCA). The various types of manifesting in the form of petechiae, purpura and PLCA are: more common macular, papular types and; ecchymoses due to infiltration of blood vessel walls by the rare nodular form.4-5 Nodular form has been shown amyloid deposits is not very common.2,9 Here we are toprogresstosystemicformofamyloidosis.Therecent presenting a case of AL amyloidosis with skin descriptive studies have noted that rate of progression involvementintheformofpapulareruptions. of nodular form to systemic amyloidosis is actually much lower than the 50% rate quoted in the literature Case summary. A 45 years old female presented with in past.6 Skin may also be involved in systemic generalized weakness, easy fatiguability, along with amyloidosis. Systemic amyloidosis is classified into progressive exertional shortness of breath and primary, secondary and familial. Primary systemic awareness of increase in the size of the tongue. She MediterrJHematolInfectDis2013;5;OpenJournalSystem also noticed skin lesions over eyelids and on lower negative. Free light chain assay was within normal chest. On evaluation, she had macroglossia [Figure limits –free kappa-15.8mg/ml (Normal range: 3.3-19.4 1(a, b)]. There were multiple, non-itchy, papular mg/ml), free lambda -16.4mg/ml (Normal range: 5.7- lesionsinlowereyelidsandlowerchestwallbilaterally 26.33mg/ml). Bone Marrow biopsy showed 10% [Figure 1(c, d)]. Cardiac auscultation revealed plasma cells. She was started on chemotherapy presence of RVS . Other system examination revealed (Melphalan, prednisolone and thalidomide). Two 4 no abnormality. Hemogram and biochemical weeks after discharge, she presented with right sided parameters were within normal limits. Urine routine weakness. Computed tomography head showed acute and microscopic examination was also normal. 2-D infarct in left basal ganglia and internal capsule. She Echocardiography showed concentrically thickened was managed conservativelyanddischarged. ventricles, diastolic dysfunction on doppler and increased echogenicity of the myocardium; overall Discussion. Cutaneous manifestation in AL findings suggestive of restrictive physiology with amyloidosis depends upon the site of amyloid normal left ventricularsystolic function.Abdominal fat deposition.2 Superficial dermal deposition of amyloid pad aspiration was negative for amyloid deposits. A produces shiny waxy translucent papules. Flexural biopsy from skin lesions over chest wall showed pink areas are sites of predilection, including the eyelids, acellular eosinophilic homogenous material in the retroauricular region, neck, axillae, inframammary dermis on haemotoxylin & eosin staining (Figure 2). area, umbilicus, inguinal and anogenital regions. This pink eosinophilic material showed pale orange Lesions may also be found on the central face, lips, positivity with congo red staining consistent with the tongue and buccal mucosa.2 Our patient had multiple diagnosis of amyloidosis (Figure 3). There was skin colored papules over lower eyelid and chest wall persistence ofKMnO4stainingsuggestingdiagnosis of ininframammaryarea.Abiopsyfromskinlesionsover primary amyloidosis. Urine and serum protein chest wall was consistent with the diagnosis of electrophoresis as well as serum immunofixation was Figure1.Photographsshowing(a)enlargedtonguewith(b)teethmarksoverthelateralmarginand(c,d)multiple,papularlesionsover lowerchestwall MediterrJHematolInfectDis2013;5:OpenJournalSystem index patient is pathognomic of AL amyloidosis and is seeninaround10%ofpatients.15 Subcutaneous abdominal fat aspiration, the preferred method for detecting systemic amyloidosis, has a sensitivity of 80%.16,17 In index case abdominal fat pad aspiration was negative for amyloid deposits. The various reasons for false negative results of this diagnostic test in index case could be: insufficient amount of material, inadequate staining technique, improperuseofpolarizinginstruments,andinsufficient light intensity. Therefore, in case of negative findings in the fat aspirate from a patient with a persistently high clinical suspicion of amyloidosis or progressive disease for which there is no other explanation, fat aspiration should be repeated, and the aspirate should Figure2.Microphotographshowingpinkeosinophilichomogenous be examined by a experienced cytopathologist. Biopsy materialinthedermis,H&EX20 is also very important for the diagnosis. Hematoxylin and eosin staining suggests the possibility of amyloidosis but Congo red staining confirms the diagnosis. Congo red staining results in a brick red color of amyloid when seen under ordinary light and under polarized light shows classical green birefringence.1-3 Serum protein electrophoresis reveals a spike pattern in around half of patients with primary AL amyloidosis. Two-thirds of patients with AL amyloidosis show monoclonal protein on immunoelectrophoresis of serum and urine respectively. The frequency of patients with an identifiable monoclonal protein rises to about 86% on screeningofbothserumandurinetogether.2Diagnostic sensitivity improves further on combining immunofixation on agarose gel electrophoresis and Figure 3. Pink eosinophilic material showing pale orange bone marrow plasma cell light chain ratio analysis.18 positivitywithCongoredstainX400 Nevertheless, in some cases with the clinical features amyloidosis showing deposits of material which were of AL amyloidosis it is not possible to demonstrate a positive for Congo red staining. There was persistence paraprotein,aswasnotedinindexpatientaswell.19 of KMnO4 staining suggesting diagnosis of primary This case demonstrates uncommon type of skin amyloidosis.10,11 Other rare cutaneous alterations seen manifestationsinthe formof papules overlower eyelid in AL amyloidosis are: hyperpigmentation, infiltrate and chest wall. A skin biopsy from these lesions will similar to scleroderma, alopecia areata or universal, substantiate the diagnosis of amyloidosis as was seen nail dystrophies, cutis laxa and lesions similar to cutis inindexcase. verticis girata in the scalp.12-14Macroglossia as seen in References: 1. FalkRH,ComenzoRL,SkinnerM.Thesystemicamyloidoses.N BabilasP.Cutaneousamyloidosesandsystemicamyloidoseswith EnglJMed.1997;337:898-909. cutaneous involvement. Eur J Dermatol. 2010;20:152- 2. BreathnachSM.MetabolicandNutritionalDisorders.In:BurnsT, 60. PMid:20071301 Breathnach S, Cox N, Griffiths C, editors. Rook's Textbook of 6. KalajianA,WaldmanM,KnableAL.Nodularprimarylocalized Dermatology. 7 th ed. Oxford: Blackwell publishing; 2004. p. cutaneousamyloidosisaftertrauma:acasereportanddiscussionof 57.36-57.51 therateofprogressiontosystemicamyloidosis.JAmAcad 3. 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