Q:

7/6/2017
70 year-old man, fibrose retro peritoneal 10 years ago well treated with prednisone. Atypical rheumatoid arthritis concerning the feet only: pain and swelling well controlled only with prednisone 5 mg and dexa tresortil (indocid+dexamethasone) one capsule every day for 4 years. Two 2 years ago there was a presence of bilateral foot ulcers 2, 3 every side very painful with no healing looking like pyoderma gangrenosum. The lab results: positives for SR - CRP- ANA- RF. I would like to have clarifications concerning this case. The following medicine did not improve the situation: dapsone - cortisone- sulfalazine - plaquenil.

A:

It would be helpful in a case this complex to have some specifics related to the laboratory results. Rheumatoid arthritis affecting only the feet is unlikely and I suspect there is another cause of the foot pain. The development of foot ulcers raises the possibilities of neuropathy and vasculitis. The retroperitoneal fibrosis is likely related to the current problems. The differential diagnosis includes IgG4 disease, carcinoid, histocytoses, drug therapy (methysergide, bromocriptine, ergotamine, methyldopa, hydralazine, beta blockers, etanercept), aortitis, amyloidosis. The ulcers suggest vasculitis including large vessel disease with ischemia as well as small vessel disease.

I suggest you confirm vascular flow to the lower extremities. I would consider a biopsy unless the lesions are classic for pyoderma gangrenosum.

I would suggest antineutrophil cytoplasmic antibody testing, measuring IgG4, hypercoagulability particularly antiphospholipid testing, cryoglobulins, immunofixation for monoclonal gammopathy, urine for protein, evaluation for inflammatory bowel disease.

Treatment choices will hinge on the results of the above. If pyoderma gangrenosum is confirmed without vasculitis then I would consider topical calcineurin inhibitors, systemic corticosteroids 1-2 mg/kg possibly with azathioprine or mycophenolate mofetil, systemic calcineurin inhibitors (cyclosporine 4-5 mg/kg), infliximab therapy (5 mg/kg initially, 2 weeks later, 4 weeks later and every 6-8 weeks if response observed).

I have provided some references related to the therapies.

Comparison of the two most commonly used treatments for pyoderma gangrenosum: results of the STOP GAP randomized control trial.
Ormerod AD, Thomas KS, Craig FE, Mitchell E, Greenlaw N, Norrie J, Mason JM, Walton S, Johnston GA, Williams HC, UK Dermatology Clinical Trials Network’s STOP GAP Team
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BMJ. 2015;350:h2958. Epub 2015 Jun 12.

OBJECTIVE: To determine whether ciclosporin is superior to prednisolone for the treatment of pyoderma gangrenosum, a painful, ulcerating skin disease with a poor evidence base for management.

DESIGN: Multicentre, parallel group, observer blind, randomised controlled trial.

SETTING: 39 UK hospitals, recruiting from June 2009 to November 2012.

PARTICIPANTS: 121 patients (73 women, mean age 54 years) with clinician diagnosed pyoderma gangrenosum. Clinical diagnosis was revised in nine participants after randomisation, leaving 112 participants in the analysis set (59 ciclosporin; 53 prednisolone).

INTERVENTION: Oral prednisolone 0.75 mg/kg/day compared with ciclosporin 4 mg/kg/day, to a maximum dose of 75 and 400 mg/day, respectively.

MAIN OUTCOME MEASURES: The primary outcome was speed of healing over six weeks, captured using digital images and assessed by blinded investigators. Secondary outcomes were time to healing, global treatment response, resolution of inflammation, self-reported pain, quality of life, number of treatment failures, adverse reactions, and time to recurrence. Outcomes were assessed at baseline and six weeks and when the ulcer had healed (to a maximum of six months).

RESULTS: Of the 112 participants, 108 had complete primary outcome data at baseline and six weeks (57 ciclosporin; 51 prednisolone). Groups were balanced at baseline. The mean (SD) speed of healing at six weeks was -0.21 (1.00) cm(2)/day in the ciclosporin group compared with -0.14 (0.42) cm(2)/day in the prednisolone group. The adjusted mean difference showed no between group difference (0.003 cm(2)/day, 95% confidence interval -0.20 to 0.21; P=0.97). By six months, ulcers had healed in 28/59 (47%) participants in the ciclosporin group compared with 25/53 (47%) in the prednisolone group. In those with healed ulcers, eight (30%) receiving ciclosporin and seven (28%) receiving prednisolone had a recurrence. Adverse reactions were similar for the two groups (68% ciclosporin and 66% prednisolone), but serious adverse reactions, especially infections, were more common in the prednisolone group.

CONCLUSION: Prednisolone and ciclosporin did not differ across a range of objective and patient reported outcomes. Treatment decisions for individual patients may be guided by the different side effect profiles of the two drugs and patient preference.

Infliximab for treatment of pyoderma gangrenosum associated with inflammatory bowel disease.
Regueiro M, Valentine J, Plevy S, Fleisher MR, Lichtenstein GR. Am J Gastroenterol. 2003;98(8):1821.

OBJECTIVES: Pyoderma gangrenosum is an immune-mediated inflammatory condition characterized by ulcerative skin lesions affecting 1-2% of patients with inflammatory bowel disease (IBD). Treatment includes wound care, antibiotics, corticosteroids, and immunomodulators. However, response to therapy varies, and many patients with pyoderma gangrenosum have disease that is refractory to these agents. The aim of this study was to assess the response of medically refractory pyoderma gangrenosum to infliximab.

METHODS: This was a multicenter retrospective study of patients with IBD and medically refractory pyoderma gangrenosum treated with infliximab. Data collected included the following: baseline demographics; duration of IBD; history of bowel resection; duration of skin lesions; number, size, and location of pyoderma gangrenosum lesions; prior medications; dose and number of infliximab infusions; bowel activity before and after infliximab; pyoderma gangrenosum activity before and after infliximab therapy; time to response and time to healing of pyoderma gangrenosum lesions; recurrence of pyoderma gangrenosum after infliximab; corticosteroid taper; and adverse reactions to infliximab.

RESULTS: There were 13 patients with moderate to severe pyoderma gangrenosum and IBD treated with infliximab. All patients demonstrated complete healing of the skin lesions. Three patients had a complete response to induction infliximab therapy and did not require additional treatment. Ten patients responded to induction infliximab and have maintained pyoderma gangrenosum healing with infusions every 4-12 wk. All patients receiving corticosteroids were able to discontinue them completely after institution of infliximab treatment. Infliximab was well tolerated; the only treatment-related adverse events were sunburn in one patient and an infusion reaction in another.

CONCLUSIONS: Infliximab is a safe and effective treatment for IBD-associated pyoderma gangrenosum

Treatment of idiopathic pyoderma gangrenosum with infliximab: induction dosing regimen or on-demand therapy?
Adişen E, OztaşM, Gürer MA
Dermatology. 2008;216(2):163-5. Epub 2008 Jan 23.

Pyoderma gangrenosum is an ulcerative skin disease of unknown origin. Recently tumor necrosis factor alpha inhibitors have been gaining attention in the treatment of recalcitrant pyoderma gangrenosum. However, there is a lack of an optimal dosing strategy in the published literature about the treatment of idiopathic pyoderma gangrenosum, and this is responsible for substantially different treatment strategies. Therefore, it is necessary to report experiences in this patient population in order to develop an optimal dosing strategy and to clarify whether regularly scheduled or on-demand therapy is suitable for idiopathic pyoderma gangrenosum. Herein we report a recalcitrant case of an idiopathic pyoderma gangrenosum treated successfully with a dosing regimen similar to the one that has been used in psoriasis. By doing so, we were capable of controlling the disease and improving the quality of life in our patient.

I hope this information is of help to you and your patient.

All my best.
Dennis K. Ledford, MD, FAAAAI

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