坏疽性脓皮病诊疗研究进展

坏疽性脓皮病(PG)是一种罕见的嗜中性粒细胞皮病,由触发炎症级联后的异常中性粒细胞聚集引起的,主要表现为无菌性中性粒细胞浸润和全身性炎症。最新研究表明药物会引起坏疽性脓皮病,但是相关报道较少,临床工作者对其认识不足。临床中PG易被误诊为难愈合性溃疡而进行清创术治疗,导致病变区扩散恶化,因此正确诊断PG对于疾病的治疗和预后十分重要。本文就PG的诊疗进展进行综述。     

坏疽性脓皮病发病机制的研究进展

 坏疽性脓皮病(PG)是一种病因不明的嗜中性皮肤病。近年来研究显示，MEFV、PSTPIP-1、NOD2、Ptpn6等易感基因可能与PG相关，中性粒细胞功能障碍、补体系统异常、多种细胞因子（如TNF-α、IL-1α、IL-1β、IL-8、IL-17和IL-25等）分泌的异常亦在PG的发病中起着关键作用。本文就近年来PG发病机制中可能存在的遗传易感因素、免疫异常方面的研究进展作一综述。     

Treatment of a relapsing facial pyoderma gangrenosum (malignant pyoderma)

A case of rapidly relapsing pyoderma gangrenosum (PG) of the left preauricular area with no undermined borders is described. This might be considered a case of malignant pyoderma (PM), a rare variety of PG. Five months after complete healing obtained with systemic corticosteroids, the preauricular lesion of PG relapsed. As retreatment with oral methylprednisolone induced glucose intolerance and high arterial pressure, sulfa drugs were initially employed with a transitory recovery of the skin lesion. A successive prolonged course with minocycline induced a new complete resolution. To date, at six months' follow‐up, the patient is relapse‐free. This case confirms that sulfa drugs and minocycline may also be considered alternative therapies in PM. PM is a variety of PG characterized by specific morphological features, a higher tendency to relapse, and poor responsiveness to treatment.     

Direct immunofluorescence in pyoderma gangrenosum

Direct immunofluorescence was done in fifty-one cases of pyoderma gangrenosum. Biopsy specimens were taken from the peripheral erythematous zone of the lesion. In thirty-one cases (61%), there was positive immunofluorescence, with perivascular deposition of immune reactants being the most frequent pattern (twenty-seven cases). These findings support a vasculitic pathogenesis of pyoderma gangrenosum.     

Granulomatous pyoderma gangrenosum: two unusual cases showing necrotizing granulomatous inflammation

We present two cases of pyoderma gangrenosum (PG) with unusual histopathological findings. The main histopathological feature of PG is usually massive neutrophilic infiltration; the neutrophil is thus the cytologic hallmark of PG. The occurrence of vasculitis is controversial. In our patients, in contrast, biopsy specimens revealed extensive granulomatous inflammation with massive tissue necrosis throughout the entire dermis and subcutaneous tissue and vascular involvement simulating many other granulomatous diseases. However, there was no evidence of systemic disease. Our cases may therefore represent a histopathologically distinct subset of PG.     

坏疽性脓皮病11例临床分析报告

报告１１例坏疽性脓皮病，均有不同程度皮肤损害，伴发热等全身症状和其它脏器累及，其中以肺部累及较为突出。对本病的治疗应在了解全身病情的基础上以全身使用皮质类固醇激素为主，控制剂量相当于强地松０．５￣１ｍｇ（ｋｇ．ｄ），必要时辅助应用免疫抑制剂，及时处理并发症。全身用抗生素只有辅助作用，局部治疗有利于控制感染和促进皮损愈合。     

Infliximab for peristomal pyoderma gangrenosum

Peristomal pyoderma gangrenosum (PPG) is a variant of pyoderma gangrenosum (PG) that is more refractory to treatment. It is a cause of severe morbidity and poses a therapeutic challenge for the clinician. Infliximab (Remicade(R); Centocor, Malvern, PA, USA) is a chimeric monoclonal antibody directed against tumour necrosis factor-alpha that has been proven to be effective in the treatment of inflammatory bowel disease (IBD) and rheumatoid arthritis. Currently, very few reports exist documenting its use in the treatment of PG and none in the treatment of PPG. We describe our experience of treating three patients with IBD-associated PPG with infliximab. All patients tolerated the drug without significant side-effects. Two patients with PPG recovered completely following the administration of infliximab, and one patient had a partial response to the drug. We conclude that infliximab appears to be a safe and effective therapeutic alternative in patients with PPG.     

An interesting case of pyoderma gangrenosum with immature hystiocytoid neutrophils

We present a unique case of a 36‐year‐old male who developed more than 20 pyoderma gangrenosum (PG) ulcers showing on histopathology a dense inflammatory infiltrate composed of histiocytoid mononuclear immature cells with a strong positivity for myeloperoxidase and Leder stain, suggesting a myeloid lineage in the absence of a concomitant myeloproliferative disorder. Histiocytoid Sweet syndrome (SS) is now recognized as a histological subtype of SS. Although PG and SS belong to the spectrum of neutrophilic diseases, to the best of our knowledge, this is the first case of a “Histiocytoid pyoderma gangrenosum” encompassing immature granulocytes in the absence of leukemia cutis.     

Genital pyoderma gangrenosum: Report of two cases and published work review of Japanese cases

Pyoderma gangrenosum is an ulcerative skin disorder showing characteristic non‐infectious ulcers and affects the lower extremities in approximately 70% of cases. Pyoderma gangrenosum is commonly associated with systemic diseases such as inflammatory bowel disease, rheumatoid arthritis and hematological malignancies. Herein, we report two cases of Japanese patients diagnosed with genital pyoderma gangrenosum. Case 1 was a 74‐year‐old woman without associated systemic complications, whose skin lesion resembled a squamous cell carcinoma and was limited to the vulva. Case 2 is an 89‐year‐old man, who suffered from myelodysplastic syndrome and acute myeloid leukemia, and presented with penile and leg ulcers mimicking pressure sores. Both cases responded well to systemic steroids. We review 13 genital pyoderma gangrenosum cases (76.9% male; aged 30–89 years) from 1996 to 2012 in Japan, including 11 previously reported cases and the present study's two cases. Four of the 13 genital pyoderma gangrenosum cases had associated systemic diseases and their skin lesions spread to the extragenital areas. Eight of the remaining nine genitalia‐localized pyoderma gangrenosum cases had no associated systemic diseases. In conclusion, genital pyoderma gangrenosum is rare and may be misdiagnosed. It should therefore be considered in cases of refractory genital ulcers. In addition, genitalia‐localized pyoderma gangrenosum tends to be without systemic complications.     

Pathergic pyoderma gangrenosum in a venous ulcer

A 74-year-old woman was referred to our department in December 1999 for a pyoderma gangrenosum (PG) arising at the edges of chronic leg ulcer. The history was positive for benign monoclonal gammopathy, ischemic hypertensive cardiopathy, polyarthrosis and venous lower leg deficiency. Monoclonal gammopathy of IgA Kappa type was diagnosed 10 years before with a continued benign nature. In 1990 a post traumatic PG of the left leg was diagnosed and a therapy with Cyclosporine A was started with healing of the lesion. In June 1999, 6 months before the hospitalization, a typical venous ulcer of the right leg appeared and was treated with bed-rest, compression bandaging and topical desloughing therapy. In the last month, after a minor surgical debridement of the wound, the lesion developed pustules evolving into a painful, necrotic ulcer with ragged, purple-red, undetermined borders (Fig. 1). A relapse of PG was suspected. Histological examination was consistent with pyoderma gangrenosum and showed massive neutrophilic infiltration, hemorrhage and necrosis of the overlying epidermis. Wound culture was negative. Other laboratory examinations only showed IgA = 8.15 g/L. Investigation of other underlying medical conditions were normal or negative. The venous leg ulcer gradually healed with antiseptic and compression-bandage therapy. After a 4-month course of topical steroid therapy with good results, the PG recurred also involving the proximal area of the leg. Methylprednisolone 50 mg/day was started. Healing began 10 days later and 2 months later the wound healed and epithelialized. Steroid was reduce to 5 mg daily for 4 months. No recurrence was seen when the drug was stopped.     

Penile pyoderma gangrenosum

We present a case of penile pyoderma gangrenosum (PG) that responded dramatically to an 8-week course of prednisone and has not recurred over a 6-month period. Although quite uncommon, penile PG should be a diagnostic consideration in any patient with non-healing ulcerative lesions of the penis. A correct diagnosis in this situation precludes unnecessary or harmful therapeutic interventions and leads to proper management.     

Sarcoidosis and pyoderma gangrenosum: an exceptional association. The role of trauma and immunosuppressive agents

The coexistence of sarcoidosis and pyoderma gangrenosum has rarely been reported. We have found only three cases in our review of the literature. Herein, we report a new case and discuss the role of trauma and immunosuppression in the development of PG, and the efficacy of cyclosporin A in PG and sarcoidosis.     

Treatment of pyoderma gangrenosum

Critical to the proper management of pyoderma gangrenosum are correct diagnosis, identification and treatment of any underlying disorder, and the proper choice of topical and systemic therapy. Many agents are available for the treatment of pyoderma gangrenosum. We review the current therapeutic options, their efficacy and side effects, and we offer some guidelines for their proper selection.     

Pediatric facial pyoderma gangrenosum preceding the diagnosis of inflammatory bowel disease

We describe two adolescent patients with pyoderma gangrenosum (PG) involving the face. Subsequent gastrointestinal evaluation revealed microscopic bowel inflammation suggestive of inflammatory bowel disease. While PG is rarely localized to the face, this brief report reveals two cases of pediatric facial PG and suggests a correlation between facial PG and microscopic colitis.     

浅表性大疱型坏疽性脓皮病

报告1例浅表性大疱型坏疽性脓皮病。患者女，58岁。四肢红斑、水疱、溃疡伴疼痛9d入院。组织病理表现为表皮内有一大脓疱，脓疱两侧表皮内有较多中性粒细胞侵入，两侧表皮有明显细胞间及细胞内水肿，真皮浅层及中层有弥漫性中性粒细胞浸润，有明显核尘，核碎裂，真皮胶原纤维间水肿，皮下组织有部分区域出血。类似于典型坏疽性脓皮病，但是在真皮中的位置更表浅。给予小剂量糖皮质激素，米诺环素，雷公藤多苷治疗，2个月后痊愈。     

Paraneoplastic pyoderma gangrenosum in solid organ malignancy: a literature review

Pyoderma gangrenosum (PG) is a rare destructive, ulcerative, and inflammatory cutaneous disease. PG can be associated with inflammatory bowel disease (IBD), arthritis, autoinflammatory syndromes, and hematological malignancies. Multiple reports in the literature have found an association between PG and solid organ tumors. This article provides a summary and review of PG in patients with solid organ malignancies. We performed a PubMed search using the terms pyoderma gangrenosum, paraneoplastic pyoderma gangrenosum, cancer, malignancy, tumor, and solid organ malignancy. Out of 529 papers screened, 19 relevant cases were included that reported patients above the age of 12 years old with antecedent, coincident, or subsequent occurrence of PG in association with a solid organ malignancy. The most common malignancies associated with PG were found in the breast (n = 6, 31.6%). In a majority of the cases, the site of PG was found to be the lower extremities (n = 12, 63.2%). Almost all cases were presented with ulcerative PG subtype (n = 18, 94.7%). Moreover, 78.9% of cases (n = 15) were reported to have PG prior to tumor diagnosis. PG lesions resolved in 100% of patients after either tumor or PG-specific treatment. We identified a strong temporal relationship between ulcerative PG and its associated solid organ malignancy. Other associations with breast cancer and lower extremity location exist but are not as strong.     

Management of pyoderma gangrenosum

The management of pyoderma gangrenosum (PG) requires a structured approach to establishing diagnosis of the disease and assessment of the patient. Clinical management of active PG lesions should be carried out in coordination with other specialists (such as nurses and pain managers) and often necessitates a flexible, innovate attitude to therapy, because the needs of individual patients may vary widely. Although there is no single successful treatment for this disease, certain types of PG lesions are recognized to respond more readily to accepted therapies than others. We outline guidelines to the management of the patient with PG and discuss alternative therapies.     

Resolution of chronic recurrent pyoderma gangrenosum with latent tuberculosis treatment

We present a 14‐year‐old male with chronic, recurrent pyoderma gangrenosum that resolved after treatment of latent tuberculosis. As pyoderma gangrenosum often occurs secondary to underlying diseases, we describe latent tuberculosis as a possible trigger for pyoderma gangrenosum.     

Deposits of complement and immunoglobulins in vessel walls in pyoderma gangrenosum

Previous immunofluorescence studies on pyoderma gangrenosum (PG) proved negative. Biopsies from the ulcer edge of 8 patients with PG were examined by immunofluorescence microscopy. Deposits of complement C3 were seen in the vessel walls of all samples, IgM in three and IgA in one. Granular deposits of C3 were seen at the dermal--epidermal junction in 2 patients. Biopsies from clinically normal skin of 6 of the patients were negative. It is suggested that deposition of immune complexes in the dermal vessel walls may play a role in the pathogenesis of PG.     

Rare association of pyoderma gangrenosum and palmoplantar pustulosis: A case report and review of the previous works

Pyoderma gangrenosum is a rare inflammatory, ulcerative skin disease that mainly involves the lower extremities. It frequently occurs in association with systemic diseases such as inflammatory bowel disease, myeloproliferative disorders and rheumatoid arthritis. Palmoplantar pustulosis is also an inflammatory dermatosis characterized by recurrent sterile pustules localized on the palms and soles. These two dermatoses are histologically characterized by neutrophilic infiltration into the lesional skin. Co‐occurrence of pyoderma gangrenosum and palmoplantar pustulosis in a single patient is extremely rare. We report a case of pyoderma gangrenosum occurred in a patient with palmoplantar pustulosis, with a review of the previously reported cases. A 68‐year‐old Japanese woman with a 10‐year history of palmoplantar pustulosis developed a skin ulcer on the left lower leg. The ulcer was diagnosed as pyoderma gangrenosum based on the clinical and histological findings, and rapidly improved in response to oral prednisolone. In addition to our case, five cases with palmoplantar pustulosis who developed pyoderma gangrenosum have been reported. These cases were thought to have some characteristics in common, such as marked female predominance, no association with inflammatory bowel disease and myeloproliferative disorders, and good response to less aggressive therapy. The co‐occurrence of pyoderma gangrenosum and palmoplantar pustulosis in our case may have an etiological link, rather than being a coincidental complication.