To the Editor: A 62-year-old woman presented to the dermatology department with a 5-month history of multiple painless cutaneous abscesses and ulcers [Figure 1A], occurring 1 month after a transvaginal hysterectomy due to uterine prolapse. Her general condition was good before and after the surgery, with no abnormal physical signs apart from metroptosis. She reported no fever, night sweat, cough, or abdominal pain, but 10 kg weight-loss. She has no history of diabetes, autoimmune diseases, or chronic infectious diseases. There was no similar illness in her family. Physical examination showed multiple subcutaneous nodules with fluctuation measuring 3.0–5.0 cm on the trunk and upper arms, as well as multiple cutaneous ulcers with yellow pus. No enlarged lymph node was palpated. Laboratory tests showed anemia, elevated leukocyte count, and increased C-reactive protein (CRP). Fungal and bacterial cultures of pus drained from a nonulcerative lesion were negative, while Mycobacterium avium was detected by real-time quantitative polymerase chain reaction. Purified protein derivative (PPD) test was negative and chest X-ray showed increased lung markings. Abdominal and pelvic computed tomography scan showed a mass at the vaginal stump, upper ureteral dilation, and bilateral hydronephrosis, whereas urine volume and serum creatinine were normal. Skin biopsy demonstrated granuloma with lymphocytes and neutrophils infiltration. Both acid-fast staining and periodic acid-Schiff staining of tissue for microorganisms were negative. The tentative diagnosis of disseminated nontuberculous mycobacteria (NTM) infection was made, although the evidence was not conclusive. The golden standard for diagnosing NTM is a positive culture of NTM but obtaining the result would take approximately three months and skins lesions of the patient were too severe to wait. She was empirically treated with clarithromycin, rifampicin, and ethambutol.

Figure 1:

The clinical manifestations, pathological and CT findings of the patient. (A) Multiple skin abscesses (white arrow) and ulcers on the trunk and upper arms. (B) Focal necrotizing glomerulonephritis with crescents shown in the kidney specimen (a, periodic acid-silver methenamine and Masson, original magnification ×100). A medium-sized occluded blood vessel infiltrated with histiocytes and granuloma formation in the subcutaneous tissue shown in the second skin biopsy (b, Hematoxylin and eosin staining, original magnification ×200). (C) After 93 days, the ulcers healed and the abscesses were absorbed completely, leaving scars and pigmentation. (D) Pelvic CT scan showed a mass (red arrow) at the vaginal stump before treatment. After 60 days, the pelvic mass disappeared with fibrotic strips shadow (red arrow) left. CT: Computed tomography.

After 10 days, she developed intermittent fever, anorexia, fatigue, conjunctivitis, with no new skin lesion but few changes of the original lesions. Erythrocyte sedimentation rate (ESR) and CRP continued to increase. Metagenomic next-generation sequencing (mNGS) of pus and blood came back all negative, surprisingly. Serum creatinine increased to 120 μmol/L. Urinalysis revealed heavy hematuria with 100% dysmorphic red blood cells. Serological tests showed positive proteinase 3 (PR3)–anti-neutrophil cytoplasmic antibody (ANCA) at >200 RU/mL. Sinus computed tomography (CT) found multiple sinus inflammation, and pulmonary CT showed mild interstitial changes. Kidney biopsy indicated pauci-immune focal necrotizing glomerulonephritis with crescents [Figure 1B]. Second skin biopsy at another lesion detected a medium-sized occluded blood vessel infiltrated with histiocytes and granuloma formation in subcutaneous fat [Figure 1B].

According to the 2022 American College of Rheumatology/European Alliance of Association for Rheumatology classification criteria for granulomatous with polyangiitis (GPA),[1] the patient achieved a cumulative score of 9 and the diagnosis of GPA was finally established. Anti-infectives were suspended due to drug-related abnormal liver function. Intravenous pulse methylprednisolone was given at 500 mg/day for 3 days, followed by oral prednisone at 1 mg·kg–1·day–1 and tapered gradually. Rituximab was administrated at 375 mg·m–2·week–1 for three times. During follow-up, the patient exhibited a complete healing of skin lesions [Figure 1C], negative urinalysis, a dropped titer of PR3-ANCA, normal ESR and CRP, and the remaining fibrotic tissue of the pelvic mass [Figure 1D].

GPA is one phenotype of anti-neutrophil cytoplasmic antibodies associated vasculitis (AAV). Skin involvements are seen in 35–50% patients with GPA,[2] characterized as petechiae or purpura distributed on the limbs and face, with pathological manifestations of leukocytoclastic vasculitis, extravascular granuloma, and mixed inflammatory patterns.

In this case, the patient initially presented with multiple cutaneous abscesses and ulcers in atypical sites after surgery, along with the pelvic mass, as well as the positive quantitative polymerase chain reaction test of the pus and granulomatous skin pathological manifestation, making it difficult to distinguish vasculitis from disseminated infection. The relationship between infection and AAV is complex. Infection is considered to be an important risk factor for the development of AAV.[3] Additionally, atypical pathogenic infections, like leprosy, may masquerade as AAV, which has been reported in a previous case.[4] Whether NTM infection was the trigger of GPA or an occasional false-positive result in this case remained puzzling. However, the satisfying response to GPA treatment without anti-NTM drugs suggested no evidence of NTM infection in the late stage. Besides infection, trauma including abrasions or surgery[5] potentially causes exposure of neutrophil cytoplasmic autoantigens to the immune system and triggers GPA, which should also be considered in this case.

The presence of multiple abscesses after surgery always suggests infection in clinical practice. However, in patients with multiple systemic involvements and poor response to anti-infectives, further test for ANCA and differential diagnosis of GPA are recommended.

Declaration of patient consent

The authors certify that they have obtained the appropriate patient consent form. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal her identity, but anonymity cannot be guaranteed.

Conflicts of interest

None.

References 1. Robson JC, Grayson PC, Ponte C, Suppiah R, Craven A, Judge A, et al. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for granulomatosis with polyangiitis. Ann Rheum Dis 2022;81:315–320. doi: 10.1136/annrheumdis-2021-221795. 2. Micheletti RG, Chiesa Fuxench Z, Craven A, Watts RA, Luqmani RA, Merkel PA, et al. Cutaneous manifestations of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheumatol 2020;72:1741–1747. doi: 10.1002/art.41310. 3. Zhao WM, Wang ZJ, Shi R, Zhu YY, Zhang S, Wang RF, et al. Environmental factors influencing the risk of ANCA-associated vasculitis. Front Immunol 2022;13:991256. doi: 10.3389/fimmu.2022.991256. 4. Yu SN, Wang J, Zheng R, Liu Y. Recurrent fever and cutaneous nodules: Leprosy masquerading as anti-neutrophil cytoplasmic antibodies associated vasculitis. Chin Med J 2020;133:2004–2006. doi: 10.1097/cm9.0000000000000937. 5. Deng S, Xing Y, Wang H, Kong X. Relapsing granulomatosis with polyangiitis provoked by trauma: A case report. Medicine (Baltimore) 2019;98:e14189. doi: 10.1097/MD.0000000000014189.