57-year-old male patient with no history of importance, beginning two months prior to admission with general malaise, myalgia, pleuritic left chest pain and coughing with green phlegm; he went to the family physician who initially treated him with amoxicillin and ibuprofen and saw some improvement. The patient continued presenting the symptoms as well as fever without chills and constitutional syndrome, losing 10kg, so he decided to visit a private clinic (PC).

While in the PC, antibiotics (amoxicillin/clavulanic acid and levofloxacin) were started, and an associated infectious process ruled out (blood, urine, cerebrospinal fluid cultures and serology were negative for virus and bacteria). He progressed unfavorably with persistent fever, lymphadenopathy and splenomegaly with laboratory tests showing pancytopenia, hyperferritinemia, elevated liver enzymes and renal failure, all progressive, so for these reasons he was transferred to our hospitals hematology department.

At our hospital treatment with antibiotics was continued but no remission of fever was seen, with progressive worsening of pancytopenia, renal failure and hepatitis; hypertriglyceridemia was also added. Biopsy of a lymph node showed no signs of malignancy and a BM biopsy evidenced only showed macrophages was performed. LHH of uncertain etiology was diagnosed. Treatment was initiated with immunoglobulin and high-dose corticosteroids with improvement seen at the beginning. Subsequently the patient presented antinuclear antibody 1/640 with a homogeneous pattern and high titer anti-DNA, so the patient was sent to rheumatology.

After assessment by rheumatology and reviewing the patients medical history, we documented urine sediment with hematuria, pyuria, proteinuria and granular casts, hypocomplementemia, a direct Coombs test without evidence of hemolysis and a pericardial effusion seen on an echocardiogram performed at the PC. The diagnosis of HS secondary to SLE was reached and the patient was transferred to the department of rheumatology.

During admission in rheumatology, intermittent arthritis, facial erythema, oral ulcers, proteinuria 2.4g/day and persistent pancytopenia was seen, so cyclosporine 3mg/kg/day was added, with improvement. Renal biopsy was performed before discharge, showing glomerulonephritis stage iii.

16-year-old male patient who began two months prior to admission with a constitutional syndrome with loss of 13kg, night sweats, afternoon fever, severe asthenia and rash on the chest, seen by the Infectious Diseases Unit, receiving empirical treatment with tetracycline without improvement.

On admission, the patient was feverish and had cervical lymphadenopathy. Initially tuberculosis was ruled out and the possibility of a lymphoproliferative disorder considered, so a BM and a lymph node biopsy were performed with negative results. The patient presented positive serology for Rickettsia which was interpreted as a false positive, and positive serology for Leishmania (IgG 1/256); amphotericin B was installed for 5 days at 3mg/kg/day, with improvement at the beginning, but leading to elevated pancreatic enzymes, therefore obliging its suspension due to secondary pancreatitis. Furthermore, during admission, ANA >1/1280, anti-DNA >600, positive anti-ENA, anti-Scl70 and anti-histones were seen, so an evaluation by Rheumatology was sought. Treatment was initiated with corticosteroids 1mg/kg/day for suspected connective tissue disease, with initial improvement and remission of fever.

In spite of amphotericin B suspension and continuing with corticosteroids, the patient presented abdominal pain, vomiting, worsening of pancreatic enzymes levels, fever and a generalized seizure. We performed a cranial CT with contrast which was normal and an abdominal CT with contrast, showing splenic infarcts, hepatomegaly, increased abdominal lymphadenopathy and free peritoneal fluid in the Douglas recess, so we decided to transfer the patient to Intensive Care Medicine (ICM). While in the Infectious Diseases Unit the patient presented anemia, leukopenia, lymphopenia, acute hepatitis and hypocomplementemia, the BM biopsy reported a slightly hypercellular marrow without evidence of infiltration and increased macrophages with some phagocytosis but not regarded as hemophagocytic; he was also treated with antibiotic, ceftriaxone and piperacillin–tazobactam.

While in ICM we began cyclosporine 3mg/kg/day for suspected SLE or SHSH, with improvement at the beginning. The general examination on admission revealed generalized muscle atrophy, mobile painless lymphadenopathy, oral ulcers, swollen abdomen but no resistance, macules on the trunk and livedo reticularis on the skin of the lower extremities, as well as anuria. The laboratory studies showed worsening of the data described, with further hyperferritinemia and elevated LDH. Blood cultures, stool cultures, urine and cerebrospinal fluid cultures were negative and he was serologically negative for viruses and bacteria, presenting negative DNA for Leishmania.

HS secondary to SLE complicated with multiple organ dysfunction syndrome was diagnosed. Treatment with antibiotics, corticosteroids, cyclosporine, and immunoglobulins was continued and anakinra was added. The outcome was favorable, with complete neurological recovery and progressive decrease of the analytical parameters. Later, during his stay in ICM he presented sinus tachycardia and bradyarrhythmias attributed to cardiotoxicity due to cyclosporine, which was suspended.

Regarding HS, he progressed well, but then presented specific bacterial peritonitis which required antibiotics and suspension of anakinra. The patient was discharged from ICM and sent home due to improvement, but was readmitted within 7 days for worsening of the infection, requiring four surgical peritoneal lavages, discharged from General Surgery and subsequently discharged from the hospital.

Both patients had prolonged fever unresponsive to broad-spectrum antibiotics. During admission, any associated infectious process was discarded. Both patients met 7 of the 9 criteria for LHH. The 2 tests that were not met were quantifying natural killer cells and sIL-2 receptor, tests that are not performed at our center.

The authors state that no experiments were performed on persons or animals for this study.

The authors state that they have followed their workplace protocols regarding the publication of patient data and all patients included in the study have received enough information and have given their written informed consent to participate in the study.

The authors state that they have obtained informed consent from patients and/or subjects referred to in this article. This document is in the possession of the corresponding author.