1 Introduction

The introduction of biological therapy in treating Crohn's disease has changed the management of severe Crohn's and affected its outcome. However, with the used of biologics many adverse effects have been encountered. These adverse effects include infections, which may become severe enough and lead to stopping the medication. We are reporting a case of Crohn's disease treated with biological therapy, presented with a persistent skin lesion that was treated as pyoderma gangrenosum and turned out to be a cutaneous leishmaniasis.

2 Case report

A 55-year-old Libyan lady with 7-year history of Crohn's disease presented with painful swelling of 18 months duration, the swelling was located over the pubic area with multiple persistent ulcerations and it was discharging pus. The skin lesion initially arises on the left side of the pubic area then it progresses to involve parts of the labia majora. This lesion was developed while she was on infliximab 400 mg intravenous infusion every 8 weeks and azathioprine 125 mg/day, and mesalamine 4 g per day.

Swab for culture and sensitivity revealed a klebsiella infection that was sensitive to amikacin. For that reason, she was treated with a 2 weeks course of intravenous amikacin with no improvement in her skin condition. Later on, the diagnosis of pyoderma gangrenosum was suggested and slow tapered systemic steroid was initiated, the patient did not report any improvement. At that time, we decided to send her for a skin biopsy. Biopsy of the lesion showed psoriasiform epidermal hyperplasia (defined as epidermal hyperplasia with elongation of rete ridges in a regular manner), the upper dermis showed a scar tissue formation with perivascular lympho-plasmacytic infiltrate (defined as mono/polymorphonuclear cells around at least 50% of the circumference of a vessel wall). The lower derms contained mixed inflammatory infiltrate containing the Donovan bodies, which are multiple rounded pink structures that were positive with Giemsa stain located inside the macrophages, in close relation with the Russel bodies, which are eosinophilic spherical or globular cytoplasmic inclusions that located in the rough endoplasmic reticulum. Taking this picture put the diagnosis of cutaneous leishmaniasis on the top of our list. Back to her social history she lives in Benghazi, Libya, she is a teacher and a mother of 4 sons and a daughter. In addition, her blood tests including complete blood count, coagulation profile, liver function, kidney function, iron, ferritin, C-reactive protein, erythrocyte sedimentation rate, total proteins were all normal. Abdominal ultrasound scan and chest X-ray were normal. Unfortunately, serological antibodies and PCR for Leishmania DNA were not available for further confirmation. However; the Infliximab was withheld and the patient received oral voriconazole 200 mg per day for 30 days along with intralesional infiltrations of pentavalent antimonials and cryotherapy leading to complete resolution of the clinical picture and left only mild residual scars (Figs. 1, 2).

Fig. 1
figure 1

Swollen multiple ulcerated lesions located over the pubic area, with diffuse erythema and induration

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Fig. 2
figure 2

The same lesion after treatment with anti-leishmania drugs

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3 Discussion

Leishmaniasis is a vector-borne infectious disease caused by parasites of the genus leishmania, there are three clinical forms of the disease: visceral, cutaneous and mucocutaneous leishmaniasis. More than 20 species of Leishmania parasite are responsible for the disease. The infection is transmitted by the female sandflies. This disease is endemic in the Mediterranean region, which includes the northern parts of Libya [1].

Clinical presentation ranges from mild cutaneous disease to a life threatening visceral form. However, the clinical presentation can be quite variable and challenging especially in the immunosuppressed patient since the clinical findings are depending particularly on the host immunity rather than the parasite itself, making misdiagnosis with other skin infections, inflammatory or malignant conditions a common problem in the clinical practice [2, 3].

One of the risk factors to get an overt disease is to have an immune suppressive states, such as those who are on immunosuppressive medications. Antitumor necrosis factor (TNF) alpha are one of the immune suppressive medications that used to treat inflammatory bowel disease and these drugs have been associated with increased risk for infections as well as the reactivation of some latent infections including leishmaniasis [4].

Recently many cases of leishmaniasis have been reported in patients being treated with biological therapy, and these reports included cutaneous, mucocutaneous and visceral involvement. However, cases of cutaneous leishmaniasis in a Crohn's disease patient treated with biological therapy are still few [1,2,3,4,5].

The diagnosis of leishmaniasis can be very tricky, since the confirmation of the diagnosis is based on the visualization of the Leishmania parasite using the microscopic examination of Giemsa-stained specimens. In addition, culture and PCR of the parasite DNA are used for species identification.

Screening for latent Leishmania infection in asymptomatic patients prior to prescribing biological therapy maybe indicated in the endemic areas, especially in those with a known immunosuppressive state [2,3,4].

According to a survey on asymptomatic Leishmania infection in inflammatory bowel disease patients receiving biological therapy, the prevalence of Leishmania asymptomatic infection was similar to that in healthy populations at the same endemic area. Furthermore, in those living in an endemic area a positive serological test alone might not be enough to initiate treatment. Unlike the recommendation on preventing mycobacterium tuberculosis, the current guidelines for anti-TNF-alpha therapy do not recommend preventing leishmaniasis [5]. However, many case reports have been reported on leishmania opportunistic infection among those treated with anti-TNF-alpha, particularly with infliximab and adalimumab, most of them were 1–3 years after initiation of therapy [5, 6].

Atypical clinical presentations of the disease were observed in patients receiving anti-TNF who lived in the endemic areas, in addition; atypical histological pictures were also reported, that include larger and multiple lesions with smaller number of parasites. In these cases the confirmation of the disease was achieved by checking serological testing, skin PCR testing and the response to anti- leishmania treatment [3, 5, 7, 8].

In our case, the lack of the serological or PCR testing, the good response after holding the biological therapy and starting the anti- leishmania medications made us confirm the diagnosis of cutaneous leishmaniasis.

It is not very unusual for Crohn's disease patients to be presented with skin manifestation such as pyoderma gangrenousum or metastatic Crohn's which may minic cutaneous leishmaniasis. However, cutaneous leishmaniasis should be considered in case of persistent ulcerated skin lesion in a patient under treatment with biological therapy.

In conclusion, with the increased use of the anti-TNF medications for the treatment of inflammatory bowel disease in areas where leishmaniasis is an endemic disease; physicians should consider cutaneous leishmaniasis as a possible cause of unresponsive skin ulceration in patients with Crohn's disease being treating with biological therapy.