Pyoderma gangrenosum adverse event with Rituximab use: A postmarketing pharmacovigilance analysis

Rituximab is a monoclonal antibody that is used for the treatment of certain malignancies and autoimmune conditions. Pyoderma gangrenosum is a rare painful ulcer that can be fatal in some cases and can also reoccur after treatment. The objective of this paper was to analyze whether a statistically significant signal exists between Rituximab and pyoderma gangrenosum in the Food and Drug Administration Adverse Event Reporting System (FAERS). A disproportionality analysis was carried out on cases from January 1, 2004 to March 31, 2019 in the FAERS. Frequentist methods of relative reporting ratio, reporting odds ratio (ROR), and proportional reporting ratio (PRR) and the Bayesian‐based IC₀₂₅ metric were used in order to assess the adverse event signal. Thirty‐two cases were found in FAERS in which the drug Rituximab was administered and pyoderma gangrenosum was reported as an adverse event. The lower 95% CI of the information component was 0.97, the lower 95% CI of ROR was 2.18, the PRR was 3.09 and Chi‐squared was 42.16, which indicates a statistically significant signal. The signal is supported by six case reports in the literature that describe a total of 14 patients who developed pyoderma gangrenosum after Rituximab administration. When administering Rituximab, clinicians should monitor for the occurrence of symptoms representing pyoderma gangrenosum.     

Efficacy and safety of etanercept for postoperative pyoderma gangrenosum after infliximab serum sickness

Non‐peristomal postoperative pyoderma gangrenosum (PPG) is a rare subtype of pyoderma gangrenosum that occurs in the early postoperative period at surgical incisions, most commonly after breast surgery. Early diagnosis and treatment is essential to prevent severe scaring. TNF‐alpha inhibitor infliximab was reported to be efficient in treatment of PPG refractory to systemic corticosteroids. However infliximab can be not well tolerated. We report the first case of etanercept efficacy in post‐plastic breast surgery pyoderma gangrenosum after infliximab serum sickness.     

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.     

Concurrent Hidradenitis Suppurativa,Inflammatory Acne,Dissecting Cellulitis of the Scalp,and Pyoderma Gangrenosum in a 16‐Year‐Old Boy

We report the case of a 16‐year‐old boy who presented to our clinic with concomitant hidradenitis suppurativa, inflammatory acne, dissecting cellulitis of the scalp, and pyoderma gangrenosum. Recent reports describe the co‐occurrence of pyoderma gangrenosum, acne, and hidradenitis suppurativa. This case further expands the spectrum of concomitant pyoderma gangrenosum and dissecting cellulitis of the scalp.     

Pulmonary nodules and nodular scleritis in a teenager with superficial granulomatous pyoderma gangrenosum

Superficial granulomatous pyoderma gangrenosum, a rare variant of pyoderma gangrenosum, has been considered to be the most benign form of the disease. We present the case of a 15‐year‐old boy with pulmonary involvement and nodular scleritis associated with this unusual type of pyoderma gangrenosum and discuss its differential diagnosis.     

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.     

Pyoderma gangrenosum and adrenocortical carcinoma

Systemic disorders that have been associated with pyoderma gangrenosum include inflammatory bowel disease, rheumatoid arthritis, paraproteinemias, and hematologic malignancies. We report the case of a 55-year-old woman with pyoderma gangrenosum, IgA monoclonal gammopathy, and a cortisol-secreting adrenocortical carcinoma. Review of the literature revealed one previous case of pyoderma gangrenosum associated with a solid tumor; at autopsy, a carcinoid tumor and an adrenocortical adenoma were found. Our patient's rapid improvement after the carcinoma was resected and her subsequent disease-free course suggests that the two conditions were related. This case suggests that evaluation for underlying malignancy should be considered in patients with pyoderma gangrenosum.     

Pyoderma gangrenosum with pulmonary involvement?

Pyoderma gangrenosum is a rare, painful, noninfectious, ulcerative, reactive neutrophilic skin condition. It is characterized by ulcers that can spread quickly showing undermined violaceous borders. Since there is no single diagnostic test, early diagnosis is always challenging. The aggressive nature of classical pyoderma gangrenosum may become apparent only with time. Pulmonary involvement of pyoderma gangrenosum maybe underreported. We describe a case of classical pyoderma gangrenosum in a 65-year-old man with pulmonary involvement, who presented with a painful fluctuate nodule and ulcer with mucopurulent and hemorrhagic exudates, and with a monoclonal gammopathy, IgA type. One month later the ulcer and hemoptysis all disappeared after treatment with glucocorticosteroids. The pulmonary manifestations of pyoderma gangrenosum were also reviewed.     

Portable negative‐pressure wound therapy for pyoderma gangrenosum: Report of two cases

Pyoderma gangrenosum is a chronic non‐infectious neutrophilic dermatosis that causes undermining ulcers. Topical therapies for the deep ulcers of pyoderma gangrenosum have not been established. To investigate whether negative‐pressure wound therapy is effective for a pyoderma gangrenosum ulcer, we used the PICO single use negative‐pressure wound therapy system (Smith & Nephew, London, UK) for two pyoderma gangrenosum patients. In these cases, the ulcers decreased in size and necrolytic tissue was removed notably. Moreover, there were no secondary infections nor was there Koebner phenomena. Our cases suggest that portable negative‐pressure wound therapy can be a treatment option for deep, intractable ulcers caused by pyoderma gangrenosum. Because portable negative‐pressure wound therapy devices afford increased mobility to patients, they can give the patient a better quality of life than standard negative‐pressure wound therapy systems do.     

Pyoderma gangrenosum as an early revelator of acute leukemia

Bullous pyoderma gangrenosum is an atypical, more superficial variety of the classical pyoderma and is often associated with myeloproliferative disorders. We present the case of a patient who presented initially with subcutaneous nodules and who developed bullous lesions afterwards. Histological evaluation showed the presence of neutrophilic infiltrates in both lesions. A few months after the diagnosis of bullous pyoderma gangrenosum, an underlying leukemia was revealed. Our case illustrates the importance of regular blood and bone marrow examinations in patients with atypical bullous pyoderma gangrenosum, resulting in a rapid diagnosis of the underlying disease.     

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.     

Superficial granulomatous pyoderma treated with intravenous immunoglobulin

Superficial granulomatous pyoderma is a rare variant of pyoderma gangrenosum. The superficial ulceration and vegetative margins are clinically distinctive; the suppurative and granulomatous histology is characteristic, though not pathognomonic. The condition is said to be relatively benign and more responsive to treatment than classic pyoderma gangrenosum, though published evidence of this is not always convincing. We present a case of superficial granulomatous pyoderma that was unusually aggressive, but that underwent dramatic and lasting resolution after intravenous immunoglobulin therapy.     

Superficial granulomatous pyoderma: a case in an 11-year-old girl and review of the literature

Superficial granulomatous pyoderma is a rare entity thought to be a variant of pyoderma gangrenosum and is often mistaken for classic pyoderma gangrenosum. Superficial granulomatous pyoderma has mainly been described in adults. We describe a case of Superficial granulomatous pyoderma in an 11-year-old girl and present a review of the literature. Superficial granulomatous pyoderma maintains clinical and histopathologic characteristics distinct from classic pyoderma gangrenosum and has a more favorable prognosis. It is often responsive to conservative treatment.     

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.     

Psoriasis vulgaris als Trigger eines superfiziellen multilokulären Pyoderma gangraenosum?

We report on a 60-year-old man with psoriasis vulgaris who had developed disseminated ulcerations of different sizes over the complete integument over a period of 3 months. The initial examination revealed approximately 150 clearly defined ulcerations, which were mostly reported to be painless. The histopathology report of a biopsy taken from the border area of an ulceration showed a nonspecific inflammation with a predominantly neutrophilic infiltrate. In the synopsis of all results, after excluding relevant differential diagnoses, we diagnosed a superficial multilocular pyoderma gangrenosum that had possibly developed in the areas of the preexisting psoriasis vulgaris. Reports of superficial multilocular pyoderma gangrenosum, a variation of pyoderma gangrenosum, are extremely rare. This condition is characterised by multiple superficial, chronically persistent ulcerations. These ulcerations are often described as indolent and usually develop from a pustule in the area of a preexisting condition or trauma. Up to now, psoriasis vulgaris has seldom been described as a trigger for pyoderma gangrenosum. The treatment is very difficult and is based on local and/or systemic immunosuppression. In this patient's case, considerable improvement was attained with a topical polyhexanide gel in combination with moist wound therapy, with no systemic immunosuppression. Our case report underscores that physicians should keep in mind the rare variation of superficial multilocular pyoderma gangrenosum in the differential diagnosis of multiple disseminated, painless ulcerations over the complete integument in patients with psoriasis vulgaris.     

Familial ulcerative pyoderma gangrenosum: a report of 2 kindred

Pyoderma gangrenosum is a rare, chronic ulcerative skin disease. It is a diagnosis of exclusion, after ruling out other causes of cutaneous ulceration. The etiology of pyoderma gangrenosum is poorly understood but is likely multifactorial. We describe 2 families affected by ulcerative pyoderma gangrenosum. This familial clustering suggests a possible genetic role in the development of pyoderma gangrenosum in some cases.     

Tumor necrosis factor-alpha inhibitors and acne fulminans: Friend or foe?

Acne fulminans (AF) is an uncommon variant of inflammatory acne with abrupt eruption of painful nodules, pustules, and hemorrhagic ulcerations, often associated with systemic symptoms. Paradoxical adverse reactions to tumor necrosis (TNF)-alpha inhibitors have been reported, and rare cutaneous complications include pyoderma gangrenosum, Sweet syndrome-like hypersensitivity eruptions, and pustular folliculitis. We report an unusual case of AF in a patient with Crohn disease that worsened with doses of adalimumab, which is considered a second-line treatment for AF. This case highlights that acneiform eruptions may be an underreported paradoxical adverse reaction to anti-TNF alpha therapy.     

Pyoderma gangrenosum or cutaneous lymphoma: a difficult clinical diagnosis

Pyoderma gangrenosum is frequently associated with an underlying condition such as ulcerative colitis or a myeloproliferative syndrome. However, lymphoproliferative malignancies have only rarely been seen concurrently with pyoderma gangrenosum. We present the case of a patient with small lymphocytic lymphoma who noted a slowly enlarging skin ulcer that was clinically consistent with pyoderma gangrenosum. Examination of a biopsy specimen showed infiltration of the skin with lymphoma cells as well as deeper necrotic material and thrombosis of vessels that were infiltrated by lymphoma. This case illustrates the difficulty of differentiating pyoderma gangrenosum from cutaneous lymphoma clinically.     

Pyoderma gangrenosum in a patient with bullous systemic lupus erythematosus

We report a 55-year-old woman with bullous systemic lupus erythematosus, who later developed pyoderma gangrenosum (PG). Dapsone was effective for the eruption of bullous bullous systemic lupus erythematosus but not for pyoderma gangrenosum. Cyclosporine was effective for the skin lesions of pyoderma gangrenosum. This is the first reported case of PG associated with bullous systemic lupus erythematosus.     

Autoinflammatory syndromes associated with hidradenitis suppurativa and/or acne

Autoinflammatory syndromes associated with hidradenitis suppurativa (HS) and/or acne are rare but potentially debilitating disorders if not diagnosed and treated correctly. They share a common pathogenesis involving a dysregulated innate immune system with abnormal interleukin (IL)‐1 signaling leading to sterile neutrophilic inflammation. The clinical features are recurrent episodes of fever, painful arthritis, and skin lesions consistent with HS, acne, and pyoderma gangrenosum (PG) accompanied by elevated systemic inflammatory markers in blood. So far, several clinically different syndromes have been reported in the literature including pyoderma gangrenosum, acne, and pyogenic arthritis (PAPA), pyoderma gangrenosum, acne, and hidradenitis suppurativa (PASH), pyoderma gangrenosum, acne, and spondyloarthritis (PASS), pyoderma gangrenosum, acne, pyogenic arthritis, and hidradenitis suppurativa (PAPASH), psoriatic arthritis, pyoderma gangrenosum, acne, and hidradenitis suppurativa (PsAPASH), and pyoderma gangrenosum, acne, and ulcerative colitis (PAC). The rarity of the syndromes complicates the establishment of evidence‐based treatment guidelines. Furthermore, treatment can be challenging due to lack of response to standard treatment modalities. Therefore, it is important to increase the awareness about these diseases in order to optimize disease management and ultimately improve the quality of life of patients.