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Cutaneous Vasculitis After Renal Transplantation: A Case Report

S. Rau, A. Wollenberg, M. Weiss, M. Fischereder, and U. Schönermarck

ABSTRACT

Background. Cutaneous vasculitis is a rare symptom after renal transplantation. With abroad spectrum of differential diagnosis, the new appearance of a skin rash in transplantedpatients can be challenging.Case Report. We present the case of a 69-year-old man with palpable purpura, skinulcerations, and diffuse arthralgias. He had a history of cadaveric renal transplantationowing to biopsy-proven isolated immunoglobulin (Ig)A nephropathy and never sufferedfrom any skin manifestation before. Skin biopsy confirmed Henoch–Schoenlein purpura(HSP), which developed under maintenance immunsuppressive therapy with tacrolimusand mycophenolate mofetil. Renal biopsy showed recurrent IgA nephropathy with positivemesangial and capillary IgA staining.Discussion. This is the first case to describe a new manifestation of HSP following renaltransplantation owing to isolated IgA nephropathy. Here, we summarize the differentialdiagnosis of cutaneous vasculitis following renal transplantation. Moreover we give a shortreview of the recurrence of IgA nephropathy and HSP after renal transplantation followed

by possible strategies for prevention and therapy of recurrent disease.

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CUTANEOUS Vasculitis is a rare symptom after renaltransplantation. With a broad spectrum of differential

iagnosis, the new appearance of a skin rash in transplantedatients can be challenging. Vasculitis is defined by theresence of inflammatory leukocytes in vessel walls withesulting organ damage and may occur as a primary processr be secondary to an underlying disease. Manifestation inhe skin is often the initial presentation of a systemicasculitis, with leukocytoclastic vasculitis being the mostommon histopathologic manifestation. Based on currentata, cutaneous vasculitis in an average population isssociated with the following conditions: Idiopathic (45%–5%), infection (15%–20%), inflammatory/immunologicisease (15%–20%), drug intake (10%–15%), and malig-ancy (�5%).1 After renal transplantation, cutaneous vas-ulitis can also indicate recurrence of the underlying renalisease.Diagnosing and classifying cutaneous vasculitis in a trans-

lanted patient can be difficult. The prompt recognition andreatment of associated disorders is essential for appropri-te patient management. In general, rational diagnosingncludes an exact medical history, physical examination,aboratory investigation, and finally skin biopsy.

The present paper reports the case of a patient, who

nderwent renal transplantation owing to biopsy-proven

0041-1345/12/$–see front matterhttp://dx.doi.org/10.1016/j.transproceed.2012.04.037

3048

mmunoglobulin (Ig)A nephropathy. He developed cutane-us vasculitis while on immunosuppressive therapy withacrolimus and mycophenolate mofetil.

CASE REPORT

A 69-year-old man presented to the hospital with palpable purpuraof all limbs, skin ulcerations, and diffuse arthralgias. Travel historywas unremarkable. He had no dyspnae, fever, or diarrhea. Thepatient had a history of IgA nephropathy, which was diagnosed byrenal biopsy several years ago. Despite intensive therapy withsteroids and cyclophosphamide, he developed end-stage renaldisease. After 2 years of hemodialysis he underwent cadaveric renaltransplantation. The initial immunosuppressive regimen consistedof tacrolimus, mycophenolate mofetil, and steroids. Steroids were

From the Department I of Internal Medicine (S.R., M.F., U.S.),Nephrology Division, Ludwig Maximilians University, Munich,Germany; Department of Dermatology and Allergy (A.W.), Lud-wig Maximilians University, Munich, Germany; and Departmentof Pathology (M.W.), Ludwig Maximilians University, Munich,Germany.

Address correspondence to Dr. med. S. Rau, Department I ofInternal Medicine, Nephrology Division, University Hospital Mu-nich Grosshadern, Ludwig Maximilians University Munich, Mar-chioninistr. 15, Munich, Germany. E-mail: Simon.Rau@med.uni-

muenchen.de

© 2012 by Elsevier Inc. All rights reserved.360 Park Avenue South, New York, NY 10010-1710

Transplantation Proceedings, 44, 3048–3050 (2012)

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POSTTRANSPLANTAT CUTANEOUS VASCULITIS 3049

tapered and finally stopped 6 months posttransplantation. Baselineserum creatinine was 1.6 mg/dL (141 �mol/L).

This admission to hospital occured 21 months after transplanta-tion. Current medications included tacrolimus, mycophenolatemofetil, amlodipine, metoprolol, and pantoprazole. Additionaldiagnoses were arterial hypertension and a deep vein thrombosis inthe past. On admission, his blood pressure was 130/70 mmHg, pulserate was 90 beats/min, temperature was 36.5°C and oxygen satura-tion on room air was 97%. On clinical examination, he presentedwith palpable purpura of all limbs combined with ulcerations andepidermolysis of the skin (Fig 1). Auscultation of lungs and heartwas normal. Laboratory investigations were remarkable for aserum creatinine of 2.1 mg/dL (184 �mol/L estimated glomerularfiltration rate, 34 mL/min), elevated white blood cells (12.4 g/L),thrombocytes (366g/L), and C-reactive protein (22.6 mg/dL). Urineanalysis indicated mild proteinuria (0.3 g/g creatinine) and hema-turia (50/�L) without leukocytes, casts, or acanthocytes. Chestx-ray and transthoracic echocardiogram were normal.

A skin biopsy of the right lower limb was performed. Histologyshowed a leukocytoclastic vasculitis with perivascular lymphohis-tiocytic infiltrates (Fig 2). Direct immunofluorescence confirmeddeposition of complement C3, IgA, and fibrinogen in the subepi-dermal vessels which is pathognomonic of Henoch–Schoenleinpurpura (HSP). Renal biopsy, which was performed later on,showed positive mesangial and capillary staining for IgA as in IgAnephropathy. There were no signs for acute or chronic allograftrejection (Fig 3).

Therapy was started with 100 mg prednisolone orally per day andpiperacillin/tazobactam IV was prescribed to avoid bacterial super-infection. The skin lesions improved rapidly and the prednisolonedosage could be continuously tapered. The patient was dischargedfrom hospital after 13 days with a serum creatinine of 1.4 mg/dL(123 �mlo/L). Because of recurrent renal IgA staining an angio-tensin-converting enzyme inhibitor was introduced for blockage ofthe renin angiotensin system (RAS).

On follow-up examination 4 weeks after discharge, serum creat-inine was stable at 1.5 mg/dL (132 �mol/L) and the skin lesionswere hardly visible. Hematuria or proteinuria was no longerdetectable. Immunosuppressive therapy was continued with tacroli-mus, mycophenolate mofetil, and a permanent prednisolone main-tenance therapy of 5 mg/d. By the reintroduction of low-dosesteroids, there were no further signs of cutaneous vasculitis.

Fig 1. Skin lesions. Palpable purpura combined with ulcer-

tions and epidermolysis of the skin.

DISCUSSION

After renal transplantation, cutaneous vasculitis is mainlydue to infectious complications or drug-related side effects,but it may also indicate the recurrence of the original,underlying disease. Our patient underwent renal transplan-tation for isolated IgA nephropathy. Before being trans-planted, he never suffered from any skin manifestation,arthralgia, or abdominal pain. Therefore, criteria for diag-nosing HSP were not fulfilled before transplantation. This isthe first case to describe a new manifestation of HSPfollowing renal transplantation owing to isolated IgA ne-phropathy. Noteably, the cutaneous vasculitis, classified as

Fig 2. Skin biopsy. Leukocytoclastic vasculitis with perivascu-lar lymphohistiocytic infiltrates (original magnification �40).

Fig 3. Renal biopsy. IgA nephropathy with positive mesangial

and capillary staining for IgA (original magnification �400).

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3050 RAU, WOLLENBERG, WEISS ET AL

HSP by skin biopsy, developed under immunosuppressionwith tacrolimus and mycophenolate mofetil.

IgA nephropathy is the most common form of glomeru-lonephritis in adults. It is characterized by isolated IgAdeposition in the glomerulus without systemic involvement.Exact recurrence rates and the true incidence of significantgraft dysfunction from recurrent disease remain unclear,but in general there is no difference in overall graft survivalin patients with IgA nephropathy compared with that ofpatients with other forms of glomerulonephritis or nonglo-merular disease.2

HSP is often considered to be a systemic form of IgAnephropathy. Renal histology is indistinguishable from IgAnephropathy. However, in HSP IgA immune complexes arenot only found in the kidney but within different organsystems, mainly affecting small arterial vessels in the skin,kidneys, and the intestinal tract. Therefore, the diseasetypically presents with palpable purpura, arthralgia, abdom-inal pain, and renal disease. HSP is the most common formof systemic vasculitis in children; most cases occur in thepediatric age group. There are few data regarding recur-rence rates of HSP after transplantation, but as in IgAnephropathy, patients with rapid pretransplant deteriora-tion, are more likely to develop recurrence in the allograft.3

There is no evidence that the type of maintenanceimmunosuppressive agent used affects the likelihood ofrecurrence and there are no prospective studies concerningthe treatment of recurrent HSP or IgA nephropathy afterrenal transplantation. Therefore, therapeutic strategiestend to be the same as in native kidneys. The best treatmentfor IgA nephropathy is currently subject to a large, ongoingstudy. The Supportive Versus Immunosuppressive Therapyof Progressive IgA nephropathy (STOP IgAN) trial aims toanswer whether, in IgA nephropathy patients, an immuno-suppressive treatment is more effective than supportivetreatment.4 As in native kidneys, treatment of recurrentdisease is mainly based on RAS blockage, which may delayprogression of recurrent disease. However, there is noevidence that this therapy actually improves graft survival.Although not subject of the study, results of the ongoingSTOP IgAN trial may also influence the clinical manage-ment of recurrent IgA nephropathy after transplantation inthe future.

For the treatment of HSP, most studies are performed in

the pediatric age group. In children, therapeutic strategies

ave included steroids, cyclophosphamide, azathioprine,ipyridamole, plasma exchange, intravenous immune glob-lins, and recently rituximab. Agressiveness of the therapyepends on the severity of renal involvement assessed byenal biopsy. In particular, the degree of crescent formationeems to be a good indicator of prognosis. Steroids are theost effective option for HSP in adults. The recently

ublished, multicenter, open-label trial by Pillebout et al,5

compared steroid therapy without or with cyclophosph-amide co-treatment in 54 adults with biopsy-proven HSP.There were no differences between the 2 groups with regardto complete disease remission, renal function, or protein-uria. Despite the small study population, these data suggestthat there is no benefit to adding cyclophosphamide com-pared with steroids alone in adults with severe HSP.Therefore, steroids alone seem to be the treatment ofchoice for adults with HSP.

In conclusion, this is the first case report to describe anew manifestation of HSP after renal transplantation dueto isolated IgA nephropathy. Cutaneous vasculitis devel-oped under immunosuppression with tacrolimus and myco-phenolate mofetil in the absence of steroids. One maypresume that the withdrawal of steroids might have favoredthe occurrence of HSP in this patient. Moreover, clinicalremission of the cutaneous vasculitis could be rapidlyachieved by the reintroduction of steroid therapy in ourpatient. Therefore, these patients might not be suitablecandidates for a complete steroid withdrawl after renaltransplantation.

REFERENCES

1. Fiorentino DF: Cutaneous vasculitis. J Am Acad Dermatol48:311, 2003

2. Briganti Em, Russ GR, McNeil JJ, et al: Risk of renalallograft loss from recurrent glomerulonephritis. N Engl J Med347:103, 2002

3. Meulders Q, Pirson Y, Cosyns JP, et al: Course of Henoch-Schonlein nephritis after renal transplantation. Report on tenpatients and review of the literature. Transplantation 58:1179, 1994

4. Eitner F, Ackermann D, Hilgers RD, et al: Supportive VersusImmunosuppressive Therapy of Progressive IgA nephropathy(STOP) IgAN trial: rationale and study protocol. J Nephrol 21:284,2008

5. Pillebout E, Alberti C, Guillevin L, et al: Addition of cyclo-phosphamide to steroids provides no benefit compared with ste-roids alone in treating adult patients with severe Henoch Schonlein

Purpura. Kidney Int 78:495, 2010