Disseminated Yersinia enterocolitica infection associated to Sweet’s syndrome

Abstract

We report the case of a young woman sough care for disseminated form of Yersinia enterocolitica infection (pseudoappendicitis with mesenteric lymph node, arthralgia, glomerulonephritis and hepatitis) diagnosed on Western Blot method for the detection of Yersinia antibodies. The patient also presented a rare concomitant cutaneous manifestation, as Sweet’s syndrome, confirmed histologically. Neutrophilic dermatosis is an exceptional skin features among post-infectious autoimmune disorders when encountering Yersinia enterocolitica infection in clinical practice.

Introduction

Yersiniosis is a zoonotic disease caused by Yersinia enterocolitica, a gram-negative bacillus shaped bacterium [1]. This infection is due to human transmission via the fecal-oral route after eating raw or undercooked pork contaminated with Y. enterocolitica bacteria [2]. Several cases of Yersinia transmission by an infected household pet and transfused blood products have been reported [1].

Two predominant clinical features were described in this disease: acute yersiniosis with predominance of gastrointestinal (GI) symptoms (diarrhea, nausea, vomiting and abdominal pain) and pseudoappendicitis presentation (right lower quadrant abdominal pain and fever in addition to the GI symptoms). Extra intestinal manifestations including reactive arthritis, myocarditis, and glomerulonephritis were less often reported. In some rare cases, it can caused cutaneous manifestations such as erythema nodosum [3] and exceptionally Sweet’s syndrome (SS) [3,4,5].

SS also called acute febrile neutrophilic dermatosis is an inflammatory, non-infectious skin reaction characterized clinically by tender, erythematous papules and/or plaques and/or pustules and/or nodules commonly appearing on the upper limbs, trunk, head, and neck.

We report herein the case of a young woman presented with SS confirmed histologically, nine days after onset of symptoms of Y. enterocolitica with disseminated presentation: pseudoappendicitis with mesenteric lymph node, glomerulonephritis, arthralgia, and hepatitis.

Observation

A 39-year-old woman presented to our hospital with a four days history of GI symptoms such as watery diarrhea without recurrences, abdominal pain in the right hypochondrium and psoitis. She also described a pain syndrome with frontal headache, myalgia, arthralgia without arthritis, associated to dry cough and fever (measured at 38 °C at admission). Abdominal examination revealed moderate splenomegaly and a right mesenteric lymph node (elastic, mobile, and painful) without fistula or abscess.

The patient had no medical past history or current treatment. She didn’t report any recent travel. She was non-smoker, no alcohol misusers, and no drug user.

Laboratory findings showed moderate thrombopenia of 145,000 platelets/µL (normal range 150,000–450,000 /µL) with hepatic cytolysis; aspartate aminotransferase (AST) of 140U/L (normal range 10–40 U/L), alanine aminotransferase (ALT) of 259 U/L (normal range 7–40 U/L), C-reactive protein (CRP) was high at 101 mg/L (normal range < 5 mg/L). Urinary test strip revealed hematuria and proteinuria suggesting glomerulonephritis. Abdomino-pelvic computed tomography (CT) had initially excluded appendicitis and revealed external iliac adenomegaly with splenomegaly.

Empiric treatment was started with antimicrobial drugs as intravenous (IV) ceftriaxone (1 g/day) for one week associated to azithromycin (500 mg/day) orally for 5 days. Further investigations included Toxoplasma gondii, Cytomegalovirus, Epstein-Barr virus, hepatitis A, C, E, HIV, hantavirus, Treponema pallidum and Brucella spp. serologies which were negative. The QuantiFERON-TB Gold test and peripheral blood cultures were also negative. Stool culture was not performed in absence of diarrhea during the hospitalization. Western Blot (WB) method for the detection of Yersinia antibodies (Euroimmun^®) confirms the presence of antibodies YopD and YopE (Table 1).Y. entorocolitica infection was diagnosed and the treatment was maintained. The clinical evolution was favorable at day 3 of azithromycin and twenty-four hours after ceftriaxone IV introduction. However, CRP level continued to increase at 162 mg/L (normal range < 5 mg/L). On day 5 of hospitalization, the patient presented two types of dermatological manifestations; (i) itching skin rash with papular lesions on upper limbs and chest with started on lower limbs, (Fig. 1A and B), with negative Nikolsky sign and (ii) pretibial erythema nodosum with nodules.

Fig. 1

A Multiple papular lesions on an erythematous and painful eruption with no ulcerative lesions, neither involvement of mucous membranes on upper limbs, B erythema nodosum lesions, C Light microscopy using hematoxylin and eosin stain (HES) x10, and x20 (D) showed a diffuse interstitial dermal neutrophils infiltrate, massive edema of dermal papillae, spongiosis with no necrotic keratinocytes, no interface dermatitis

Table 1 Results of the detection of anti- Yersinia enterocolitica antibodies using the western blot method on admission and follow-up after treatment

A skin biopsy of papular lesion performed showeda spongiotic dermatitis associated with necrotic keratinocytes and accompanied by a diffuse and dense neutrophilic inflammatory infiltrate, with few lymphocytes and histiocytes.

. The papillary dermis showed a massive edema; the superficial and middle dermis contains a very dense interstitial infammatory infiltrate rich in neutrophilic polynuclear accompanied by a few lymphocytes and histocytes, which confirm the diagnosis of SS (Fig. 1C and D). Beta-HCG dosage, rheumatoid factor and Ac-anti CCP were negative. Colonoscopy found a festonned adenoma resected. Position Emission Tomography (PET) imaging did not identify hypermetabolic site. Detection for CALR/CSF3R/ETNK1/JAK2/MPL/SETBP1/SF3B1 mutation was also negative. We decided to not use any anti-inflammatory steroids. Clinical and biological evolution was favorable; all symptoms disappeared with normalization of platelet count, liver function tests, and CRP normalization at day 21 (CRP at 3 mg/L).

Discussion

We reported here a typical case of GI yersinosis symptoms with diarrhea and abdominal pain, lymphadenopathy and hepatonephritis, associated to scarce cutaneous manifestations. The diagnosis was based on WB results with evident correlation of antibodies against Yersinia proteins and acute yersiniosis.Negative Brucella spp. serology, leads to eliminate false positives [6]. Y. enterocolitica infection has also been associated with Hashimoto thyroiditis and Graves Disease, which are also considered as autoimmune diseases [7].

Cutaneous lesions in Y. enterocolitica infection are infrequent and unspecific, except erythema nodosum [3]. SS is a rare manifestation of Y. entorocolitica disease. Histologically, SS is characterized by dense neutrophilic infiltrate in the dermis, such as our patient histological examination. To our best knowledge, only few cases had been reported in medical literature (Table 2). Several other agents with GI features are associated to SS including Salmonella spp., Helicobacter pylori and Campylobacter spp [8]. Most cases of SS are idiopathic, but this syndrome can also occur as a paraneoplasic manifestation, following drug/vaccine administration, associated with pregnancy, and in inflammatory diseases [9]. In our case, the SS rash appeared nine days after first symptoms, which is in line to literature data around seven to fifteen days. Cephalosporins are not described in literature as underlying causes of SS among antimicrobial drugs. SS is currently treated with systemic steroids or colchicine, as first line regimen. Spontaneous resolutions are also observed, such as in our patient [9].

Table 2 Review of literature: previous cases description of Sweet’s syndrome as manifestation of Yersinia Entorocolitica infection

Another clinical particularity was the disseminated and invasive presentation of yersiniosis in our case, with abdominal, respiratory and joint symptoms associated with glomerulonephritis and hepatitis. Disseminated forms are habitually observed in elderly people living with diabetes mellitus, cirrhosis, and hemochromatosis. In our case, peripheral blood cultures were all negative. Transthoracic echocardiogram ruled out acute endocarditis and colonoscopy didn’t identify ulcerative colitis.

Concerning the treatment, patients with isolated enteritis did not require antibiotic treatment. Whereas, in severe illness patients, trimethoprim, doxycycline and chloramphenicol were equally effective in vitro between 7 and 28 days [10]. Cefuroxime, ceftazidimide, piperacillin and gentamicin have hid in vitro susceptibility [11]. In our case, a short treatment of 5 days with IV ceftriaxone was enough to treat a Y. enterocolitica disseminated infection without bacteriemia. Finally, This case report will provide readers valuable insight into this rarely encountered autoimmune sequelae of Y. enterocolitica infections.