To the Editor,
Reactive haemophagocytic syndrome or secondary haemophagocytic lymphohistiocytosis (HLH) is a disorder of the mononuclear phagocyte system characterised by generalised, ineffective and uncontrolled histiocytic proliferation that leads to cell damage and multiple organ dysfunction with haemophagocytosis. The first description of secondary forms of this disease was by Risdall et al,1 who in 1979 described a syndrome characterised by a proliferation of histiocytes with haemophagocytic activity, associated with a viral infection. This syndrome was later described in association with infections of all types and with non-infectious diseases such as rheumatoid arthritis, lupus, leukaemia, lymphomas, myelodysplastic syndromes and carcinomas.
Its pathogenesis is still unclear, although there are several hypotheses. The development of this syndrome is likely to be due to an immunological disorder that results in uncontrolled T-lymphocyte activation,2 causing hypercytokinaemia, and consequently, excessive macrophage activation.
It is diagnosed according to the criteria in HLH-20043 and the treatment focuses on the infectious process, as well as on the use of gamma globulin and immunosuppression.4
We describe the case of a patient aged 42 years with a history of type 1 diabetes, diabetic nephropathy, and chronic renal failure who underwent a kidney-pancreas transplant (October 2010). The patient’s maintenance immunosuppressants are deltisone B, everolimus, and tacrolimus (FK) in addition to prophylaxis with valgancyclovir and trimethoprim/sulfamethoxazole (TMS). The patient experienced fever, vomiting and odynophagia for 2 weeks, and was treated with oral antibiotics. Fever, asthenia and dehydration persisted, so the patient was hospitalised. Laboratory analyses revealed pancytopoenia and renal and pancreatic dysfunction; the patient received subcutaneous insulin but not haemodialysis. Blood and urine cultures were performed, as well as a PCR (polymerase chain reaction) test for cytomegalovirus (CMV), and empirical treatment with ceftriaxone and ciprofloxacin was administered. Twenty-four hours after admission, the haemodynamic state had deteriorated severely and the patient was moved to intensive care, where all immunosuppressants except for corticosteroids were discontinued. Antibiotic coverage was increased through vancomycin, imipenem, fluconazole and ganciclovir. Seven days after admission, the patient was still feverish with positive cultures for common microbes and fungi and a negative PCR for CMV. We ordered PCR for parvovirus B19 due to the persistent pancytopoenia. The physical examination showed cutaneous and mucosal pallor, asthenia, adynamia and splenomegaly. The laboratory results were as follows: Hb: 8.6mg/dl, leukocytes: 900mm3, triglycerides: 317mg/dl; ferritin >1500mcg/l. In light of suspected haemophagocytic syndrome (5 criteria met), we performed a bone marrow biopsy, which revealed histiocytes with haemophagocytosis. The patient was treated with high doses of gamma globulin (400mg/kg) during 5 days. In the end, PCR was positive for parvovirus B19.
All of the patient’s low values improved (haematocrit 28%; Hb 9.4g/dl; leukocytes 1900mm3; platelets 203 000mm3) and immunosuppressant treatment was resumed. Pancreatic function remained weak, and the nephrology department found the renal function to be so severely affected that the patient needed haemodialysis. A kidney biopsy puncture was performed which yielded insufficient material.
At 30 days of hospitalisation, the patient was once again feverish with a headache; lumbar puncture revealed normal cerebrospinal fluid, acid-alcohol resistant bacilli (AARB) negative; PCR for CMV, herpes simplex virus, Epstein-Barr virus, cryptococcal antigenaemia all negative; adenosine deaminase at the upper cut-off level; cerebral MRI showed no lesions. The thoracic radiography showed bilateral interstitial and alveolar infiltrates, which was confirmed by thoracic CT as bilateral radiodense infiltrates; fibrobronchoscopy with bronchoalveolar lavage was performed; negative for AARB and positive for pneumocystitis carinii (PCP) when TMS treatment began. Due to the persistent fever and the lack of culture isolation in a case with pulmonary lesions, empirical treatment with isoniazid, rifampicin, ethambutol and liposomal amphotericin was administered. Another kidney biopsy puncture was performed, but graft bleeding ensued and the patient had to go to the surgical ward. Doctors decided to extirpate both grafts, and observed mesenteric adenopathies and abundant purulent matter. This matter tested AARB (+) under direct examination, and therefore antibiotic and antifungal treatments were suspended, with the patient continuing tuberculosis treatment. Final culture was positive for tuberculosis. Patient’s fever subsided and overall condition improved; he returned to his home city and is monitored by his local haemodialysis centre.
Haemophagocytic syndrome that reacts to associated infections is a severe and potentially fatal condition. Immunosuppressed patients who present with a fever and haematological abnormalities (cytopoenias) should be screened for haemophagocytosis as early diagnosis enables proper treatment and a favourable prognosis.
[P1]Las unidades son diferentes en word y pdf
