Pyoderma gangrenosum with pulmonary involvement?

ARTICLE

Auteur(s) : Ze-Hu Liu, Xue-Lian Lu, Mei-Hua Fu, Guo-Yi Zhang, Wei-Da Liu

Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Jiangwangmiao Rd 12, Nanjing, China

accepté le 16 Avril 2008

Pyoderma gangrenosum (PG) is a rare, painful, noninfectious, ulcerative, reactive neutrophilic dermatosis, which was first described in 1930 by Brunsting et al. [1]. PG has been described in association with a wide variety of disorders, including ulcerative colitis, Crohn’s disease, acute lymphoid and myeloid leukemia, myeloproliferative disease, paraproteinemia, myeloma, rheumatoid arthritis, chronic active hepatitis and human immunodeficiency virus infection [2].

The general incidence has been estimated to be between 3 and 10 per million per year in Germany [3]. Since no laboratory parameter for PG is available and the histopathology of PG is nonspecific and changes with the stage and location of lesion, early diagnosis of PG is not always easy. Many causes of cutaneous ulceration resembling PG may lead to a misdiagnosis of PG, especially in the early stages. In a recent review of skin ulcers misdiagnosed as PG, a frequency of misdiagnosis of approximately 10% was found [4]. Since the phenomenon of pathergy occurs in 20-50% cases, surgical treatment can worsen the condition. Thus, correct recognition and early diagnosis of PG is of paramount importance. Here, we report the dynamic changes of skin, pulmonary manifestation, diagnosis and successful treatment of a patient with classical PG.

Case report

He presented with a painful fluctuate nodule and an ulcer with mucopurulent and hemorrhagic exudates with a peripheral inflammatory halo of erythema (figure 2A). No history of skin trauma was found and most lesions developed de novo. Multiple thin cribriform scars due to former episodes of PG were found. Laboratory investigations included the following: complete blood cell count, urine analysis, stool routine, chemistry studies, serum IgA, IgM, IgG, antinuclear antibodies, complement factor C3 and C4, anti-neutrophil cytoplasmic antibodies(ANCA), chest X-ray, abdominal sonography, syphilis and HIV infection screen. Swabs from the ulcer were sent for microbiological examination. Nodule biopsy was performed for histopathology and microbiological study, including atypical mycobacterial, fungal and nocardia infection.

The second day the fluctuating nodule broke on the top with serum exudates and the ulcer enlarged with prominent exudate (figure 2B). The following days the red halo enlarged and many inflammatory pimples appeared on the border, which soon broke down and the ulcer evolved (figure 2C). The lesions were severely painful. Histopathology showed a lymphocytic infiltration with a neutrophilic component, fibrinoid necrosis and nuclear dust (figure 2F), which revealed leukocytoclastic vasculitis. Microbiological examinations were all negative. Laboratory investigations were normal except higher serum IgA 9.52 g/L (normal 0.7-3.7 g/L). According to the histopathology, clinical manifestations and the proposed criteria for PG [3, 5], the diagnosis of PG was made and treatment with methylprednisolone 40 mg daily and dapsone 100 mg daily was initiated. The second day after glucocorticosteroid therapy, the ulcer and red halo stopped spreading, and the ache and mucopurulent exudates significantly diminished (figure 4D), along with remission of the hemoptysis. Further screening for underlying diseases was performed. Bone marrow aspiration was normal. Pulmonary contrast computed tomographic scans showed fewer nodules and less fibrosis in both lungs (figure 1B). The concentration of urine kappa chain was 33.5 mg/L (normal < 18.5 mg/L). However, the patient refused a lung biopsy. One month later the ulcer and hemoptysis all disappeared (figure 2E). The glucocorticosteroid was tapered and follow-up continued.

Discussion

Major criteria were: 1. Rapid progression of a painful, necrolytic cutaneous ulcer with an irregular, violaceous, and undermined border, 2. Other causes of cutaneous ulceration have been excluded.

Minor criteria included: 1. History suggestive of pathergy or clinical finding of cribriform scarring, 2. Systemic diseases associated with PG, 3. Histopathologic findings (sterile dermal neutrophilia, ± mixed inflammation, ± lymphocytic vasculitis), 4. Treatment response (rapid response to systemic steroid treatment).

Since biopsies show no specific diagnostic features, the diagnosis of classical PG, based on clinical presentation and course, is one of exclusion. Conditions that may mimic PG are: systemic vasculitis (Wegner’s granulomatosis, mixed cryoglobulinemia, polyarteritis nodosa, antiphospholipid-antibody syndrome and livedo vasculitis), infections (spotrichosis, amebiasis, syphilitic ulceration, ecthyma gangrenosum and nocardiosis), ischemic ulceration and primarily T-cell lymphoma [7]. Once the diagnosis is established, it is then mandatory to explore the possibility of an extracutaneous neutrophilic involvement and of an associated disease. Underlying disease is very frequent (70%) and includes > 30% arthritis, > 30% inflammatory bowel disease, < 10% malignancy, and in 10%, monoclonal gammopathy, usually of the IgA type [8], as in our patient.

Pulmonary involvement is a characteristic feature of ANCA-associated systemic vasculitis. Pulmonary involvement in PG is rare, and is probably under-reported because the respiratory neutrophilic features are nonspecific. Few reports have described changes in the lungs. Pulmonary disease in association with PG occurred as a single unilateral opacity [9-11], interstitial pneumonitis [12], pleural effusion [13], and multiple pulmonary nodules [14-16]. The most often described pulmonary manifestation was multiple pulmonary nodules with or without cavitations, as described in our patient. As reported earlier, pulmonary and cutaneous symptoms are usually simultaneous [17]. The cutaneous and pulmonary symptoms rapidly decreased with glucocorticosteroid therapy, which revealed that the undefined pulmonary symptoms in our patient might be related to PG. The main differential diagnosis of PG is Wegener’s granulomatosis. Generally, CT-guided, fine needle lung biopsy is necessary. Histological examination of the pulmonary manifestation of PG revealed aseptic inflammatory lesions without necrotizing granulomatous inflammation and necrotizing vasculitis. In patients with PG with the presence of radiologically visible multiple pulmonary nodules, a pulmonary manifestation of the underlying disease should be considered.

The aggressive nature of classical pyoderma gangrenosum may become apparent only with time. However, pyoderma gangrenosum with pulmonary involvement is a difficult early diagnosis to make. Thus, close liaison with the chest department is therefore warranted.

Acknowledgements

References

2 Crowson AN, Mihm Jr. MC, Magro C. Pyoderma gangrenosum: a review. J Cutan Pathol 2003; 30: 97-107.

3 von den Driesch P. Pyoderma gangrenosum: a report of 44 cases with follow-up. Br J Dermatol 1997; 137: 1000-5.

4 Weenig RH, Davis MD, Dahl PR, Su WP. Skin ulcers misdiagnosed as pyoderma gangrenosum. N Engl J Med 2003; 347: 1412-8.

5 Su WP, Davis MD, Weenig RH, Powell FC, Perry HO. Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria. Int J Dermatol 2004; 43: 790-800.

6 Powell FC, Su WP, Perry HO. Pyoderma gangrenosum: classification and management. J Am Acad Dermatol 1996; 34: 395-409.

7 Conrad C, Trueb RM. Pyoderma gangrenosum. J Dtsch Dermatol Ges 2005; 3: 334-42.

8 Powell FC, Collins S. Pyoderma gangrenosum. Clin Dermatol 2000; 18: 283-93.

9 Lebbe C, Moulonguet-Michau I, Perrin P, Blanc F, Frija J, Civatte J. Steroid-responsive pyoderma gangrenosum with vulvar and pulmonary involvement. J Am Acad Dermatol 1992; 27: 623-5.

10 McCulloch AJ, McEvoy A, Jackson JD, Jarvis EH. Severe steroid responsive pneumonitis associated with pyoderma gangrenosum and ulcerative colitis. Thorax 1985; 40: 314-5.

11 Vignon-Pennamen MD, Zelinsky-Gurung A, Janssen F, Frija J, Wallach D. Pyoderma gangrenosum with pulmonary involvement. Arch Dermatol 1989; 125: 1239-42.

12 Brown TS, Marshall GS, Callen JP. Cavitating pulmonary infiltrate in an adolescent with pyoderma gangrenosum: a rarely recognized extracutaneous manifestation of a neutrophilic dermatosis. J Am Acad Dermatol 2000; 43: 108-12.

13 Wang JL, Wang JB, Zhu YJ. Pyoderma gangrenosum with lung injury. Thorax 1999; 54: 953-5.

14 Chahine B, Chenivesse C, Tillie-Leblond I, Delaporte E, Scherpereel A, Grignet JP, Tonnel AB. Pulmonary manifestations of Pyoderma gangrenosum. Presse Med 2007; 36: 1395-8.

15 Kasuga I, Yanagisawa N, Takeo C, Koga M, Kiyokawa H, Yonemaru M, Ichinose Y, Toyama K. Multiple pulmonary nodules in association with pyoderma gangrenosum. Respir Med 1997; 91: 493-5.

16 Kruger S, Piroth W, Amo Takyi B, Breuer C, Schwarz ER. Multiple aseptic pulmonary nodules with central necrosis in association with pyoderma gangrenosum. Chest 2001; 119: 977-8.

17 Wallach D, Vignon-Pennamen MD. From acute febrile neutrophilic dermatosis to neutrophilic disease: forty years of clinical research. J Am Acad Dermatol 2006; 55: 1066-71.