Excellent response to bortezomib in a patient with widespread ulcerative pyoderma gangrenosum accompanied by pulmonary involvement and IgA monoclonal gammopathy

Dear Editors,

1.

Pyoderma gangrenosum (PG) is a chronic, recurrent, neutrophilic dermatosis that can be a cutaneous manifestation of various underlying medical conditions.1 It is characterised by the sudden appearance of painful pustule, nodule, ulcer, or bullae formation on an erythematous background with violaceous, rapidly expanding borders.2 Underlying aetiologies include arthritis, internal malignancies, collagenous/vascular diseases, and haematological malignancies including monoclonal gammopathies and inflammatory bowel disease.1 Here, we present a 39‐years old woman with extensive PG and pulmonary cavitary nodules associated with IgA lambda monoclonal gammopathy.

A 39‐year‐old woman was admitted to the emergency department with a complaint of extensive vegetative plaques and exudative necrotic ulcers on the skin. Her medical history indicated that initial cutaneous lesions started 15 years ago, which were treated with cyclosporine and systemic steroids, with complete healing for about 6 years. However, she was then hospitalised for reappearance of cutaneous ulcers, and bone marrow biopsy and colonoscopy were performed and reported no abnormality. Biopsy of the skin lesions showed the presence of diffuse neutrophilic infiltration that was compatible with PG. Thereafter, cyclosporine tablets of 300 mg/d were started and stabilised the cutaneous lesions, with only two or three flares per year. After 2 years of cyclosporine treatment, the patient was admitted to our dermatology department and was switched to dapson 100‐150 mg/d for 3 years after she had chief complaints of high fever, cough, and purulent expectoration. Her chest computed tomography (CT) demonstrated parenchymal distortion, interlobular septal thickening, nodular opacities in both lungs, and minimal enlargement of both bronchi compatible with fibrosis, with differential diagnoses of organising pneumonia and fungal infection. Given that she was treated for pulmonary tuberculosis with a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol for 2 months and then subsequently with isoniazid and rifampicin for 4 months 10 years ago, she was referred to the department of chest diseases where bronchoscopy and bronchoalveolar lavage were performed. Markers related to Mycobacterium tuberculosis, cytomegalovirus, aspergillosis, and bronchoalveolar lavage fluid culture were all negative. Cytology was relevant with mixed‐type inflammatory cells without any pathological findings. However, the patient refused to attend to her follow‐up appointments and stopped dapsone 150 mg/d treatment on her own. After 4 weeks of self‐treatment cessation, she was admitted to the emergency department. On dermatological examination, large vegetative plaques and necrotic ulcers covered with yellow fibrinous exudate and haemorrhagic crusts were observed. Lesions were surrounded with violaceous borders mainly involving left thoracoabdominal and both inguinal areas (Figure 1).

Figure 1.

Large vegetative plaques and necrotic ulcers surrounded by violaceous borders on the left thoracoabdominal and both inguinal regions

A skin biopsy with prediagnoses of mainly PG but also blastomycosis‐like pyoderma, cutaneous tuberculosis, deep fungal infection, and pemphigus vegetans was planned but was refused by the patient. Consequently, she was hospitalised, where laboratory studies indicated remarkably low haemoglobin (10.7 g/dL, normal range: 11.7‐15.5 g/dL), protein (6.06 g/dL, normal range: 6.4‐8.3 g/dL), and albumin (2.3 g/dL, normal range: 3.5‐5.2 g/dL) levels and an increase in IgA levels (720 mg/dL, normal range: 82‐453 mg/dL). Rheumatological markers including antinuclear antibody, cytoplasmic antineutrophilic cytoplasmic antibody, perinuclear antineutrophilic cytoplasmic antibody, rheumatoid factor, and anti‐double‐stranded DNA (anti‐dsDNA) were all negative. Total protein level in 24‐hour urine sample was 283.75 mg/d (normal range: <80 mg/d). Protein electrophoresis of the 24‐hour urine sample showed no evidence of atypical proteins; however, serum immunofixation electrophoresis demonstrated monoclonal IgA‐lambda band in the beta‐2 area. Given that she had a history of pulmonary cavitary nodules and opacities in bilateral lungs, chest X‐ray and CT were performed and reported bronchiectasis, parenchymal consolidation, cavitary nodules, and air bronchogram formation in the upper anterior, inferior lateral, and posterior right pulmonary lobes. A subsequent bronchoalveolar lavage was performed, and studies results demonstrated no infectious aetiology and malignancy. Planned bronchoscopic biopsy, colonoscopy, and bone marrow aspiration biopsy were not performed because of a lack of patient's consent.

A multidisciplinary council of dermatology, haematology, chest, and infectious diseases departments evaluated the patient. Given that she had high IgA levels and monoclonal IgA lambda band formation in serum immunofixation electrophoresis, she was diagnosed with IgA monoclonal gammopathy in the spectrum of monoclonal gammopathy of undetermined significance. As she had been diagnosed with pulmonary tuberculosis only through pulmonary X‐ray findings 10 years ago, and M. tuberculosis was never isolated from her sputum cultures; her former and present cavitary nodules were evaluated as PG's pulmonary involvement. She was then started on bortezomib and dexamethasone chemotherapy regimen where bortezomib 2.1 mg was applied on days 1, 8, 15, and 22 subcutaneously, and oral 40 mg dexamethasone was taken on days 1, 2, 3, 4, 9, 10, 11, and 12. An additional oral 20 mg methylprednisolone tablet was given on off‐treatment days of this regimen. After the first cure, marked regression of cutaneous lesions was noted with cribriform scar formation (Figures 2 and 3). In addition, the recession of pulmonary cavitary nodules was also remarkable on the CT that was performed later (Figure 4).

Figure 2.

Regression of cutaneous ulcers and cribriform scar formation after first cure of bortezomib and dexamethasone therapy (A: before, B: after)

Figure 3.

Regression of cutaneous ulcers and cribriform scar formation after second cure of bortezomib and dexamethasone therapy (A: before, B: after)

Figure 4.

Regression of cavitary nodules. Black box showing cavitary nodule formation in the right lung (A: before treatment). Black box showing regression of cavitary nodule formation in the right lung (B: after treatment)

In the literature, there are few case reports related to patients presenting with both cutaneous ulcerative PG and cavitary nodules in lungs presenting as a manifestation of pulmonary PG and showing regression with treatment. PG accompanied by monoclonal gammopathy, mostly IgA monoclonal gammopathy, has been previously reported as well.3 Similar to the pulmonary involvement of our case, Vignon‐Pennamen et al.4 reported a patient with typical cutaneous ulcers and pulmonary abscess‐like cavities reflecting involvement of PG, which showed healing of both skin and lung lesions after corticosteroid therapy. Velasco‐Tamariz et al.5 presented a case of PG associated with IgA gammopathy showing dramatic response to bortezomib chemotherapy.

Our case is significant and extraordinary in that the patient showed extensive cutaneous vegetative ulceration mainly involving the left thoracoabdominal region and pulmonary cavitary nodules as manifestations of PG, which showed remarkable response to bortezomib treatment.

CONFLICT OF INTEREST

The authors declare no potential conflict of interest.