Acne fulminans in a young man with granulomatosis with polyangiitis (Wegener's granulomatosis): A chance association or marker of serious systemic disease?

Introduction

Granulomatosis with polyangiitis affects mainly the upper and lower respiratory system and kidneys; however, many organs including skin may be involved. About 15% of the patients have cutaneous manifestations that are specific to granulomatosis with polyangiitis. Facial involvement with pyoderma-like lesions or ulcerations and especially involvement of the periauricular area are thought to be specifically suspicious for the disorder.

Case Report

A 19-year-old man was admitted with severe joint pains and fever with bleeding from “boils” on the face of a few days' duration. The lesions were painful, engorged with blood and had appeared in crops. In the past 2 years, he had developed painful bleeding nodular lesions on the face on and off, for which he was seen by a dermatologist and treated with a course of minocycline and topical clindamycin, without much effect. He had also received a course of 20 mg of isotretinoin per day for about 8 weeks, without much improvement. There was history of nasal polypectomy, a few months before presentation. He also had fleeting joint pains involving the ankles and knees and a history of purpuric eruption on the legs that cleared spontaneously. He complained of severe fatigue and had lost 7 kg body weight in the past 2 months. There was no cough or hemoptysis.

On examination, there were multiple crusted nodules on the face, many of which were breaking down, leaving bleeding ulcers with ragged edges [Figure - 1]a and [Figure - 1]b. A provisional diagnosis of acne fulminans versus hemorrhagic nodules related to a systemic disease, mimicking nodular acne was entertained. He had a total white blood cell count of 11,200 cells/mm^[3], an erythrocyte sedimentation rate of 40 mm/1^st hour and a C-reactive protein of 80 mg/L. His rheumatoid factor, antinuclear antibody studies, hepatic and renal profile were normal. His cytoplasmic antineutrophil cytoplasmic antibody was reported as 2+ on ethanol-fixed slide by immunofluorescence. PR3 (main antigen of cytoplasmic antineutrophil cytoplasmic antibody) was strongly positive at 9.73 by ELISA.

Figure 1: (a and b): Hemorrhagic nodules mimicking nodular acne, some breaking down with crust formation and some juxtaposed with preexistent scars of acne

Commonly documented skin manifestations of granulomatosis with polyangiitis like papules, nodules on the limbs, palpable purpura, ulcers, oral ulcers, gingivitis etc., were absent. Two skin biopsies taken from the edge of an ulcerated nodule showed irregular epidermal and follicular infundibular epithelial hyperplasia with diffuse dermal infiltrate containing lymphocytes and numerous giant cells [Figure - 2]a. Follicular epithelium was hyperplastic with a dense dermal infiltrate of lymphocytes with several giant cells [Figure - 2]b. Against the backdrop of granulomatous inflammation with multiple giant cells were also some granulomas showing a central fibrinoid degeneration [Figure - 2]c and [Figure - 2]d. Computed tomography scan of paranasal sinuses and chest showed mucosal thickening of both ethmoid and maxillary sinuses and the nasal mucosa and discrete multiple angiocentric nodular opacities, respectively [Figure - 3]. His eyes, central nervous system and heart examinations were normal. His urine routine examination, urine 24-hour protein, serum creatinine and blood urea nitrogen were normal.

Figure 3: Diffuse mucosal thickening involving both maxillary sinuses with blockage of osteomeatal complexes. Mucosal thickening is seen involving bilateral ethmoid sinuses too

Clinicopathological correlation suggested a diagnosis of granulomatosis with polyangiitis presenting with hemorrhagic facial nodules mimicking nodular acne. He responded dramatically to methylprednisolone pulse of 500 mg administered intravenously for 5 days with topical mupirocin for 15 days for the lesions [Figure - 4]a and [Figure - 4]b. He was later treated with 60 mg of prednisolone and 2 g of mycofenolate mofetil. In the fifth month of treatment, he developed acute onset of painful pustular lesions studding his face and ulceration of the lobule of the ear [Figure - 5]a and [Figure - 5]b. Prednisolone was again increased to 80 mg and the lesions resolved in 3 weeks. He continued to be well with no complaints 12 months after starting therapy except for inflammatory acne-like facial nodules off and on that resolved spontaneously.

Figure 4: (a and b): Healed lesions after pulsed methylprednisolone therapy

Discussion

Granulomatosis with polyangiitis, previously known as Wegener's disease, is a rare multisystem disease. It is a form of small to medium vasculitis, and although it can affect any organ it most frequently targets the respiratory system and kidneys.^[1] The peak incidence of the disorder which has been cited as between ages of 45 and 50 years has been shown to be increasing in child and adult population.^[1],[2],[3] Data on the disorder in pediatric age group are sparse, but it is said to occur most commonly in the second decade.^[1] Skin is involved in 35%–50% of patients with Wegener's granulomatosis^[3],[4],[5] About 15% of patients have cutaneous lesions specifically associated with the disorder if one disregards those occurring secondary to infections, treatment or coexisting dermatoses unrelated to it.^[1],[2],[3] Skin manifestations of the disorder include palpable purpura, cutaneous nodules, subcutaneous nodules, papules, vesicles, petechiae, urticarial lesions, panniculitis, pyoderma gangrenosum–like lesions and Raynaud's disease.^[3],[4],[5] They are seldom seen to dominate the clinical picture.^[4] Acneiform lesions have been reported in association with the disorder in patients younger than 20 years of age. They are often the first presenting symptom in this age group.^{[1],[6],[7],[8]} Cutaneous lesions have been noted more frequently in multiorgan disease.^[1],[2] Skin lesions are thought to run their course parallel to the systemic disease and generally respond to treatment of the disorder.^[3],[4],[5] Our case gave history of developing painful acne-like eruptions on his back at 17 years of age which spontaneously resolved with scarring. He then developed facial nodules with systemic signs and symptoms that were treated by a dermatologist unsuccessfully. He had nasal symptoms which were diagnosed and treated as sinusitis and nasal polyposis and was eventually operated upon just a few months before the nodular eruption. There is only one previous report of hemorrhagic acneiform nodules occurring in a teenager in English literature but that patient seems to have had very mild lesions compared with ours.^[6] Interestingly, that patient also developed an acute pustular eruption and a destructive ulcer of the auricular lobule. Facial involvement with pyoderma-like lesions or ulcerations and especially involvement of the periauricular area are thought to be specifically suspicious for Wegener's granulomatosis [Figure - 5]b.^[2],[9] Over 50% of skin biopsies in granulomatosis with polyangiitis may yield nonspecific findings.^[4],[10] Necrotizing vasculitis, granulomatous vasculitis, extravascular palisading granulomas and leukocytoclastic vasculitis are most commonly reported.^[1],[4],[10] While evidence of some form of vasculitis helps in a definitive diagnosis of the disorder, it is not always the case and absence of it does not rule out granulomatosis with polyangiitis. Erythema nodosum–like septal granulomatous inflammation and acneiform granulomatous folliculitis have been reported.^[1] Granulomatous pathology is also encountered not infrequently and represents tissue damage. It is said to be seen most often in non-purpuric lesions.^[11] Our patient's skin biopsy from the facial nodules showed dense granulomatous infiltrate with plenty of lymphocytes and several giant cells but no evidence of vasculitis. A granuloma with central fibrinoid necrosis was also seen. This case underscores the importance of meticulously investigating patients presenting with severe acne-like lesions with associated musculoskeletal, upper airway, pulmonary or renal involvement with a high index of suspicion granulomatosis with polyangiitis. The knowledge of possibility of various presentations of acne-like lesions occurring on the face also reduces the chances of treatment with unnecessary antibiotics and topical drugs for acne. [Table - 1] shows a number of other conditions, mainly syndromes, that present with acne as a significant component.

Table 1: Other conditions presenting with severe acne

Declaration of patient consent

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

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Conflicts of interest

There are no conflicts of interest.