DR [Dermatology Reports 2011; 3:e44] [page 99] Wegener´s granulomatosis in a young patient preceded by localized cutaneous manifestations Jesper Smit,1 Jakob Lykke Poulsen,2 Jakob Sølling,3 Carsten Sauer Mikkelsen4 1Department of Infectious Diseases, Aalborg Hospital, Aarhus University Hospital, Aalborg; 2Department of Internal Medicine, Lillebaelt Hospital, Vejle; 3Department of Nephrology, Aalborg Hospital, Aarhus University Hospital, Aalborg; 4Private Practice, Bredgade 13, Broenderslev, Denmark Abstract Wegener’s granulomatosis (WG) is a rare, systemic vasculitis involving multiple organs. The clinical presentation is highly diverse, and there is considerable risk of mortality if diag- nosis and treatment are delayed. We present a case illustrating that patients with WG may ini- tially present with localized cutaneous symp- toms and signs. Introduction Wegener’s granulomatosis (WG) is an uncommon necrotizing vasculitis that most commonly affects the upper airways, lungs and kidneys, but can involve any other organ.1,2 The disease presents with varying symptoms and signs and early recognition and initiation of adequate immunomodulatory therapy are essential in limiting the potentially life-threat- ening aspects of the disorder.1,3-4 We report a case illustrating that WG may present with localized, cutaneous manifestations preceding systemic disease. Case Report An 18-year old Caucasian man presented with a painful rash on the truncus that had developed over the course of a few weeks. The patient was known to have type-1 diabetes mel- litus since the age of 8, but was otherwise healthy and reported no recent travel activity or antecedent trauma to the affected area. Objective examination of the skin revealed inflamed cystic and nodular lesions confined to the chest and left shoulder, but there was no significant suppuration or other apparent signs of infection. The condition resembled a case of severe acne, and initial histopathologi- cal examination of a skin biopsy supported this preliminary clinical diagnosis. A few weeks later the patient developed a sore throat and signs of upper respiratory tract infection including cough, dyspnoea and mild chest pain. The skin changes remained limited to the chest and shoulder but had clearly pro- gressed and now appeared as deep vasculitic ulcerations, including multiple elements more than 0.5 cm deep (Figure 1). These findings and symptoms were accompanied by several weeks of fever (up to 39.6°C), malaise and substantial unilateral facial pain, and the patient was admitted to a department of nephrology for further investigation and treat- ment. The blood leukocyte and thrombocyte counts were normal as were liver and renal function tests, but C-reactive protein (CRP) was 300 mg/L (normal range, less than 10 mg/L) and anti-neutrophil cytoplasmic antibodies includ- ing specific identification of proteinase 3 (c- ANCA/PR3-ANCA) was 223 kU/L (normal range, less than 7 kU/L). During hospitaliza- tion the patient’s kidney function was continu- ally assessed and monitored, but levels of crea- tinine and urea remained within normal ranges and examination of urine including microbiological analysis revealed no abnormal- ities. Chest X-ray examination was performed and several lung infiltrates with caverns were noted. A subsequent CT guided lung biopsy demonstrated no sign of infection, but signifi- cant inflammation of the tissue was observed, and a diagnosis of WG with concomitant mononeuritis multiplex involving the trigemi- nal nerve was established. The patient received systemic methylpred- nisolone and cyclofosfamide pulse therapy, which resulted in prompt improvement of the clinical condition and skin lesions as well as a decrease in the CRP and ANCA titers. Shortly after, however, the patient developed fever and renewed elevation of the c-ANCA/PR3-ANCA, and treatment was supplemented with ritux- imab leading to immediate resolution of symp- toms and no residual pulmonary or cutaneous sequelae on recent follow-up. Discussion Our patient initially presented with a local- ized rash on the truncus, but his condition was insidiously complicated by malaise, fever and progression of the cutaneous lesions, and ulti- mately a diagnosis of systemic WG was estab- lished. The etiology of the disease remains unknown, however, several studies suggest that infectious antigens and especially S. aureus may contribute to the pathogenesis of vasculitis in susceptible hosts.1,5 The clinical presentation of WG is complex and found to be dependent on the number of organs affected and the duration of the dis- ease. As in our case, the clinical course of WG is characterized by an initial or localized phase which may affect any organ followed by a gen- eralized or systemic phase in approximately 80% of cases.1,3 However, in most patients spe- cific cutaneous findings develop concurrently or after the onset of systemic involvement and affect the head or extremities,5 but in our case they were confined to the truncus and preced- ed systemic symptoms and signs, which has only seldomly been described.6 In WG specific cutaneous lesions are seen in approximately 15% of cases,5,6 and are usually associated with renal disease and muscu- loskeletal affection, but this was not noted in our patient. Patients may develop more than one type of cutaneous lesion and these may change over time or with treatment, but sever- al studies have identified palpable purpura as the most characteristic cutaneous lesion, and nodules, papules, ulcerations and deep erythe- ma nodusum-like subcutaneous nodules com- plete the clinical spectrum.6-8 Oral involvement is not uncommon in WG,5,7 but this was not observed in our patient during the course of the disease. In this present case the level of c-A NCA/PR3-ANCA was markedly elevated, and ANCA positivity has been found to occur in 90- 95% of cases with active WG.1,6 However, as lev- els correlate with disease activity and relapses Dermatology Reports 2011; volume 3:e44 Correspondence: Jesper Smit, Department of Infectious Diseases, Aalborg Hospital, Aarhus University Hospital, Mølleparkvej 4, P.O. Box 365, DK-9000 Aalborg, Denmark. Tel: +45.26241332. E-mail: jesm@rn.dk Key words: Wegener’s granulomatosis, cutaneous findings, case report, vasculitis, diabetes. Contributions: JS, JLP, JS, CSM, manuscript writ- ing and text reviewing. Conflict of interest: the authors have no conflict of interest. The manuscript has not been published and is not being considered for publication elsewhere. Received for publication: 14 September 2011. Accepted for publication: 22 September 2011. This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY- NC 3.0). ©Copyright J. Smit et al., 2011 Licensee PAGEPress, Italy Dermatology Reports 2011; 3:e44 doi:10.4081/dr.2011.e44 No n- co mm er cia l u se on ly [page 100] [Dermatology Reports 2011; 3:e44] in the absence of ANCA are rare, repeat testing and evaluation of blood biochemistry in order to follow the course of the disease is highly recommended. As illustrated by our case the diagnosis of WG represents a challenge and is based on anamnestic information closely correlated with clinical features, pathologic findings and ANCA testing.9 Relevant differential diagnoses are numerous and include leukocytoclastic vasculitis, Henoch-Schönlein purpura, pyoder- ma gangrenosum, lymphoma, erythema nodosum, rheumatoid arthritis, drug reac- tions, and a variety of infectious conditions.5 However, like WG, these conditions often pres- ent with varying and uncharacteristic symp- toms and signs and, as in our case, dermato- logical evaluation may provide valuable diag- nostic information. If untreated, systemic WG leads to more than 90% mortality in the first two years, hence early recognition and initiation of ade- quate immunomodulatory treatment are essential and associated with significantly decreased morbidity and mortality.1,4,10 High dose corticosteoroids and pulsed intravenous cyclofosfamide remain the mainstay of initial therapy,4 but relapse and refractory WG still represent therapeutic challenges. However, data from recent studies evaluating biological therapies, including TNF-α blockers (inflix- imab) and monoclonal antibodies (rituximab) are promising1,4 and future treatment regimes will hopefully further improve the outcome of this patient group.4 We report a case illustrating that patients with WG may initially present with localized cutaneous symptoms and signs preceding seri- ous systemic disease. Prompt recognition of the condition and initiation of early and ade- quate immunomodulatory therapy is crucial in order to reduce mortality and morbidity. Dermatologists therefore need to be aware of WG as a possible differential diagnosis, espe- cially in patients presenting with characteris- tic skin manifestations and accompanying sys- temic symptoms and signs. References 1. Schilder AM. Wegener´s Granulomatosis vasculitis and granuloma. Autoimmun Rev 2010;9:483-7. 2. Koldingsnes W, Nossent H. Epidemiology of Wegener´s granulomatosis in northern Norway. Arthritis Rheum 2000;43:2481-7. 3. Rodrigues CE, Callado MR, Nobre CA, et al. Wegener´s granulomatosis: prevalence of the initial clinical manifestations – report of six cases and review of the literature. Rev Bras Reumatol 2010;50:150-64. 4. Carruthers D, Sherlock J. Evidence-based management of ANCA vasculitis. Best Pract Res Clin Rheumatol 2009;23:367-78. 5. Gibson LE, Specks U, Homburger H. Clinical utility of ANCA tests for the der- matologist. Int J Dermatol 2003;42:859-69. 6. Comfere NI, Macaron NC, Gibson LE. Cutaneous manifestations of Wegener´s granulomatosis: a clinicopathologic study of 17 patients and correlation to antineu- trophil cytoplasmic antibody status. J Cutan Pathol 2007;34:739-47. 7. Marzano AV, Fanoni D, Berti E. Oral and cutaneous findings are valuable diagnos- tic aids in Wegener´s granulomatosis. Eur J Intern Med 2010;21:49. 8. Barksdale SK, Hallahan CW, Kerr GS, et al. Cutaneous pathology in Wegener´s granu- lomatosis. A clinicopathologic study of 75 biopsies in 46 patients. Am J Surg Pathol 1995;19:161-72. 9. Leavitt RY, Fauci AS, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Wegener´s granulomatosis. Arthritis Rheum 1990;33: 1101-7. 10. Takala JH, Kautiainen H, Leirisalo-Repo M. Survival of patients with Wegener´s granulomatosis diagnosed in Finland in 1981-2000. Scand J Rheumatol 2010;39:71- 6. Case Report Figure 1. Cystic and nodular lesions on the chest, notice necrotic wounds with element size ranging from a few millimeters up to 2 cm. In consistence with vasculitis the ele- ments are inflamed and do not blanch on pressure. No n- co mm er cia l u se on ly