Wegener Granulomatosis in a Child:Cutaneous Findings as the Presenting Signs

V. Brazzelli, M.D.,* C. Vassallo, M.D.,* F. Baldini, M.D.,* A. Ravelli, M.D.,†A. Martini, M.D.,† and G. Borroni, M.D.*

*Department of Human and Hereditary Pathology, Institute of Dermatology, and†Department of Pediatrics,University of Pavia, Pavia, Italy

Abstract: Wegener granulomatosis (WG) is a systemic disease that isparticularly unusual in children. A limited form has been described with-out renal involvement. We report a 14-year-old girl in whom the diseasestarted with acneiform nodular and papular lesions on the forehead. Laternecrotic ulcers developed on her forehead, arms, and buttocks. The cu-taneous lesions were associated with upper and lower respiratory tractinvolvement, low-grade fever and arthralgias. Subsequently clinical andlaboratory evaluations (increased ESR; leukocytosis and presence of se-rum IgG antibodies cANCA = 1:160), with chest roentgenograms revealingpulmonary densities and parenchymal infiltration, suggested the diagno-sis of WG. The histologic findings of a cutaneous biopsy specimen wereulceration of the epidermis with diffuse neutrophilic inflammatory infil-trate and a late-stage small vessel vasculitis in the dermis. Histopathol-ogy of the nasal mucosa was characterized by a granulomatous processwith a dense lymphohistiocytic infiltrate with few giant cells, a finding thatconfirmed the diagnosis of WG. No renal involvement was present. Onemonth of cyclophosphamide (125 mg/day) and prednisone (70 mg/day)therapy markedly improved the patient’s clinical condition. At present, 1year later, she is free from any signs of the disease. According to theliterature, the frequency of cutaneous lesions in WG ranges from 16% to46%. They are the presenting sign only in 6% of patients. Cutaneouslesions are even more uncommon in children. In particular, an “acne-iform” presentation is a rare finding in WG.

Wegener granulomatosis (WG) is a systemic vasculi-tis of small and medium-size vessels, affecting mostly therespiratory tract (sinuses, nose, pharynx, and lungs) andkidney, although any organ may be affected (1–3). Alimited form without renal involvement has a more fa-vorable prognosis (4). WG may occur at any age, but thepeak incidence is usually in middle-aged people (51.6

years for men and 47.2 for women with a male:femaleratio of 1.25:1) (5–7). It is rarely observed in children(8). About 50 pediatric cases have been reported to date(5,6,8,9).

We describe a young girl in whom WG presentedas nodular and necrotic acneiform skin lesions onthe forehead and later on the arms and buttocks.

Address correspondence to Giovanni Borroni, M.D., Clinica Der-matologica, Universita` di Pavia, Policlinico S. Matteo IRCCS, Pavia,Italy.

Pediatric Dermatology Vol. 16 No. 4 277–280, 1999

277

Cutaneous lesions, upper and lower respiratory tractdisease, chest roentgenograms, immunologic, labora-tory, and histologic findings led to the diagnosisof WG.

CASE REPORT

A 14-year-old girl was referred to the Department ofDermatology in Pavia for evaluation of nodular and ne-crotic acneiform lesions mostly on her forehead (Fig. 1).Later the nodules progressed to ulcers on the arms (Fig.2) and buttocks. Two months before referral the patientsuffered from persistent rhinitis, nasal ulcerations, pha-ryngotonsillitis, and bilateral, purulent otitis media thatfailed to respond to systemic antibiotic therapy anddrainage.

A biopsy specimen was obtained from a papulone-crotic lesion on the forehead. The histologic findingswere ulceration of the epidermis covered by scale crust(Fig. 3), with pseudoepitheliomatous hyperplasia at thebase. Collagen degeneration with basophilic changes anda diffuse neutrophilic inflammatory infiltrate with fewhistiocytes were present in the dermis, with late-stagesmall-vessel vasculitis (Fig. 4). Direct immunofluores-cence showed granular deposits of IgA and C3 in thewalls of dermal vessels. On histopathologic examinationof the nasal mucosa a granulomatous inflammation witha dense, lymphohistiocytic infiltrate with few giant cellswas detected (Fig. 5).

Constitutional signs and symptoms including weightloss, low-grade fever, arthralgia, chest pain, and a dis-tinctive nasal quality of voice were present. Labora-tory studies revealed an elevated ESR, moderate leuko-cytosis, and increased serum IgG antibodies againstcytoplasmic components of neutrophils (cANCA4 1:

160; negative pANCA). Chest roentgenograms revealedpulmonary densities and parenchymal infiltration involv-ing the upper lung fields. There was no renal involve-ment. A diagnosis of WG was made.

Treatment with oral cyclophosphamide 125 mg/dayand prednisone 70 mg/day led to satisfactory control ofthe clinical manifestations. At present, 1 year later, thepatient is clinically free of any sign of WG and continuestreatment with azathioprine 100 mg/day, prednisone 15mg/day, aspirin 100 mg, and trimethoprin-sulfa-methoxazole 160 + 80 mg.

Figure 1. Papular and necrotic skin lesions resemblingacne fulminans on the forehead.

Figure 3. Ulceration of the epidermis covered by scalecrust and surrounded by pseudoepitheliomatous hyper-plasia is evident. Collagen degeneration with basophilicchanges and a diffuse neutrophilic inflammatory infiltratewith few histiocytes are present in the dermis.

Figure 2. Ulcer on the left arm.

278 Pediatric Dermatology Vol. 16 No. 4 July/August 1999

DISCUSSION

Wegener granulomatosis is characterized by the clinical-histopathologic triad of necrotizing granulomas of theupper and/or lower respiratory tracts, leukocytoclasticvasculitis, and focal necrotizing glomerulitis (absent inthe limited or in the initial forms of WG) (1–3). WG isuncommon in pediatric patients; only a few cases havebeen reported under 16 years of age (6–8). Cutaneouslesions (papules, nodules, purpuric patches, palpable pur-pura, or ulcers) have been observed in 30% to 50% ofpatients during the course of the disease, while they arethe presenting sign in 8.6% to 13% of patients (6,8,9); no

single skin change is pathognomonic (10–13). Usuallythe presence of cutaneous lesions in WG may be corre-lated with a higher severity of systemic disease (13,14).

Although our patient had nodular acneiform lesions,which progressed to form ulcerative lesions on the fore-head, she had only a limited form of WG. In 1984 Chyuet al. (9) described a similar case where the lesions on theforehead were first assumed to be cystic acne.

From a histopathologic point of view, patients withgranulomatous inflammation tend to be younger and tohave visceral involvement of WG less frequently thanpatients with leukocytoclastic vasculitis (15); moreover,Hu et al. (14) suggested that this subgroup of patients hasa better prognosis. In our patient, both granulomatousinflammation of the nasal mucosa and remnants of leu-kocytoclastic vasculitis are present in cutaneous lesions.In 1993 Rottem et al. (8) studied 23 children and 135adults with WG and pointed out that at the onset of thedisease, lung involvement is significantly less commonin young patients. Our patient had pulmonary infiltrates.The presence of c-ANCA supported the diagnosis of WGand was used to assess the course of the disease (14–17).In conclusion, WG requires clinical, laboratory, andpathologic investigations for a correct diagnosis.

REFERENCES

1. Klinger H. Grenzformen der periarteritis nodosa. Z Pathol1931;42:455–480.

2. Wegener F. Uber generalisierte. Septische Geffa¨sser-krankuuger. Verh Dtsch Ges Pathol 1936;29:202–210.

3. Elder D, Elenitsas R, Jaworsky C, Johnson B Jr. Lever’shistopathology of the skin, 8th ed. Philadelphia: Lippin-cott-Raven, 1997:201–202.

4. Carrinton CB, Liebow AA. Limited forms of angiitis andgranulomatosis of Wegener’s type. Am J Med 1966;41:497–527.

5. Moorthy AV, Chesney RW, Segar WE, Groshong T. We-gener granulomatosis in childhood: prolonged survival fol-lowing cytotoxic therapy. J Pediatr 1977;91:616–618.

6. Neumann G, Benz-Bohm G, Rister M. Wegener’sgranulomatosis in childhood. Pediatr Radiol 1984;14:267–271.

7. Daoud MS, Lawrence EG, DeRemee RA, Specks U, el-Azhary RA, Su DWP. Cutaneous Wegener’s granuloma-tosis: clinical, histopathologic, and immunopathologic fea-tures of thirty patients. J Am Acad Dermatol 1994;31:605–612.

8. Rottem M, Fauci A, Hallahan CW, et al. Wegener granu-lomatosis in children and adolescents: clinical presentationand outcome. J Pediatr 1993;122:26–31.

9. Chyu JYH, Hagstrom WJ, Soltani K, Faibisoff B, WhitneyDH. Wegener’s granulomatosis in childhood: cutaneousmanifestations as the presenting signs. J Am Acad Derma-tol 1984;10:341–346.

10. Frances C, Du LT, Piette JC, et al. Wegener’s granuloma-tosis. Dermatological manifestation in 75 cases with clin-

Figure 4. Collagen degeneration with some histiocytesand remnants of leukocytoclastic vasculitis (higher mag-nification of Figure 3).

Figure 5. Lymphohistiocytic granulomatous infiltrate ofthe rhinomucosa with a few giant cells (arrow).

Brazzelli et al: Wegener Granulomatosis in a Child279

icopathologic correlation. Arch Dermatol 1994;130:861–867.

11. Patten SF, Tomecki KJ. Wegener’s granulomatosis: cuta-neous and oral mucosal disease. J Am Acad Dermatol1993;28:710–718.

12. Reed WB, Jensen AK, Konwaler BE, Hu¨nter D. The cu-taneous manifestations of Wegener’s granulomatosis. ActaDerm Venereol 1963;43:250–264.

13. Barksdale SK, Hallahan CW, Kerr GS, Fauci AS, Stern JB,Travis WD. Cutaneous pathology in Wegener’s granulo-matosis. Am J Surg Pathol 1995;19:161–172.

14. Hu CH, O’Loughlin S, Winkelmann RK. Cutaneous mani-

festations of Wegener’s granulomatosis. Arch Dermatol1977;113:175–182.

15. Hoffman GS, Kerr GS, Leavitt RY, et al. Treatment ofWegener’s granulomatosis with glucocorticoids andmethotrexate. Arthritis Rheum 1992;35:1322–1329.

16. Rao JK, Allen NB, Feussner JR, Weinberger M. A pro-spective study of antineutrophil cytoplasmic antibody (c-ANCA) and clinical criteria in diagnosing Wegener’sgranulomatosis. Lancet 1995;346:926–931.

17. Nolle B, Specks U, Ludermann J, et al. Anticytoplasmaticautoantibodies: their immunodiagnostic value in Wegen-er’s granulomatosis. Ann Intern Med 1989;11:28–40.

280 Pediatric Dermatology Vol. 16 No. 4 July/August 1999