Leishmaniamajor simulating vasculitis

Introduction

Leishmaniasis is a vector-borne disease caused by Leishmania species. The clinical spectrum is broad, ranging from cutaneous to mucocutaneous and visceral forms; manifestations depend on the infecting species and host immune response.¹ Cutaneous leishmaniasis accounts for the majority of cases, with an estimated incidence of 0.7 to 1 million cases annually in nearly 100 endemic countries.² In Israel, leishmaniasis is primarily cutaneous, with Leishmania major responsible for >80% of cases, especially in southern regions.³ Here, we report the case of a patient with L. major infection misdiagnosed as vasculitis, initially treated with corticosteroids and azathioprine, with subsequent complications and a delayed diagnosis.

Case report

A 75-year-old man presented to the dermatology department at the Sheba Medical Center, Israel, with nonpruritic, painless ulcerations on his hands and shins that had developed over 5 months. His medical history included atrial fibrillation and benign prostatic hyperplasia, treated with apixaban, bisoprolol, and tadalafil.

The patient reported a prior diagnosis of vasculitis based on clinical findings and a skin biopsy at an external center, which revealed a dermal inflammatory infiltrate in angiocentric pattern and surrounding postcapillary venules and tiny foci of fibrin seen in wall of vessels, features that are compatible with vasculitis involving small dermal vessels. Subsequently, he was treated with high-dose systemic steroids, followed by azathioprine, without improvement. Later, the patient developed an acute confusional state, attributed to steroid-induced psychosis, prompting steroid tapering, and referral for further evaluation.

On admission, physical examination was notable for deep-seated ulcers primarily on the lower limbs, featuring black eschar, yellow granulation tissue, serous exudate, well-demarcated erythematous margins, foul odor, and marked tenderness without evidence of systemic manifestations (Fig 1, A). In addition, purpuric macules were noted on the patient’s right shin.

Fig 1.

A, Deep-seated ulcers with black eschar and well-demarcated erythematous margins on the anteromedial aspects of the left thigh and shin. B, Purpuric lesion of the right shin, punch biopsy site is marked. C, Evolution of previous purpuric lesions on the right shin to deep ulcers similar to the initial presentation. D, Black eschar centers resolution and progression to yellow granulation tissue, serous exudate, and residual marginal necrotic foci.

Laboratory test results revealed elevated inflammatory markers; antinuclear antibody was positive, yielding a titer of 1:1,280 in a speckled pattern, and a slightly increased rheumatoid factor value of 32 IU/mL, with the rest of the autoimmune profile being negative. Serologies for human immunodeficiency virus, syphilis, human herpesvirus 6, adenovirus, and West Nile virus were also negative.

Punch biopsies from both purpuric and ulcerative lesions on the right shin and left thigh (Fig 1, A) revealed leishmaniasis with many Leishman-Donovan bodies (Fig 2). Real-time polymerase chain reaction test confirmed L. major as the etiologic parasite; the test was repeated, yielding the same result. However, parasite load was not quantified.

Fig 2.

A punch biopsy of a purpuric lesion in the shin. A, Superficial section. B, C, D, deep sections. A, Biopsy showed perivascular infiltrates and extravasation of erythrocytes. B, A lymphohistiocytic infiltrate can be discerned. Multiple Leishman-Donovan bodies are seen, signaled by a black arrow (C), which are more noticeable on the positive Giemsa stain, indicating Leishmania infection (D). (A-C, Hematoxylin-eosin stain; original magnifications: A, ×5; B, ×20; C, ×40; D, Giemsa stain; original magnification: D, ×40).

On further inquiry, the patient reported travel to the south region of Israel—a region endemic for leishmaniasis—and having suffered multiple insect bites. He received 10 doses of meglumine antimoniate (Glucantime), totaling 12,600 mg, without significant clinical improvement. Lesions biopsied earlier evolved from purpuric macules to ulcers over approximately 1 month (Fig 1, C).

Due to ongoing cognitive decline, a comprehensive neurologic evaluation to rule out neuroleishmaniasis was done including head computed tomography, magnetic resonance imaging, electroencephalogram, and repeat lumbar punctures that did not identify central nervous system involvement. Thus, the patient’s cognitive decline was ultimately attributed to deconditioning. Nevertheless, treatment was escalated to liposomal amphotericin B (AmBisome) for suspected central nervous system involvement. He received approximately 3 mg/kg/day intravenously, aiming for a total target dose of 20 mg/kg and received 5 doses of 200 mg, 1 dose per day, with 2 additional doses planned on days 14 and 21 after the start of treatment.

Adjunctive wound care included daily cleansing, sulfamylon cream for exudative lesions, and silverae dressings for dry wounds. Despite some improvement in skin ulcers (Fig 1, D), he did not recover to his premorbid baseline.

Discussion

Cutaneous leishmaniasis is recognized as a "great imitator," with cases misdiagnosed in documented cases, sometimes as pyoderma gangrenosum or psoriasis.4, 5, 6 To the best of our knowledge, this is a special case report in which L. major presented as purpuric lesions and was diagnosed initially as vasculitis.

In our patient, despite the lack of laboratory confirmation, neuroleishmaniasis was clinically suspected. The patient’s lack of response to first-line antimonial therapy necessitated transition to liposomal amphotericin B, chosen for its superior central nervous system penetration.^7,8

Leishmaniasis is a disease in which the outcome depends heavily on host immunity, particularly effective cell-mediated immune responses.² Immunosuppressive therapy, such as corticosteroids, anti-tumor necrosis factor-α, and blockers of other cytokines may enhance the risk of atypical, disseminated, and more severe cutaneous leishmaniasis presentations, by blocking important immunologic functions and mediators.⁹ In this case, it is plausible that the immunosuppression led to disease progression and resistance to therapy.

Insufficient clinical response to Glucantime, an antimonial therapy, may be attributed to resistance of Leishmania strains to specific therapies. For instance, Bahrami et al¹⁰ reported that antimony-resistant Leishmania tropica clinical isolates showed overexpression of iron superoxide dismutase A and B genes, supporting a mechanism in which enhanced antioxidant defense and detoxification of antimony-induced oxidative stress contribute to parasite drug resistance.

This case underscores the necessity of including infectious etiologies in the differential diagnosis of chronic ulcerative skin lesions, particularly in patients with suggestive epidemiological exposures, which should be specifically addressed. Prior immunosuppression may be an aggravating factor. Biopsy and polymerase chain reaction study should be performed, as early recognition of leishmaniasis can prevent delayed treatment and avoid the systemic complications of unnecessary immunosuppression.

Conflicts of interest

None disclosed.