gms | German Medical Science

Cancer patients especially those with hematologic malignancies are immunocompromised, not only by virtue of their disease condition but also by the immunosuppressive chemotherapy they receive. They are at great risk of all opportunistic infections, especially fungal. Mucomycosis is now emerging in an increasing incidence among neutropenic cancer patients. High incidence of suspicion is required for early diagnosis and prompt management without such, inevitable severe outcomes with disfigurement at its best and death at worst, will occur. Here we present a case of a child with Acute Myelogenous Leukemia (AML) who had vague GI symptoms followed by picture of intestinal obstruction and perforaion for which urgent exploration, resection and anastomosis were done. Pathology proved to be mucormycosis. The patient continued on systemic antifungal, both AML and mucor were controlled but the patient died later out of disease progression.

Case Report: 13 month old female patient was referred to our hospital as a case of acute leukemia. At presentation, she was febrile, pale, with multiple purpuric eruptions all over the body and had huge hepatosplenomgaly, causing mild to moderate reparatory distress. CBC was done and revealed TLC of 28.000, 54 % blasts, Hb 8.4 and platelets of 23.000, ESR 48 for 1^st hour and 86 for the 2^nd hour. Blood culture and sensitivity, CRP were drawn. Coagulation profile was tested PT 16 sec, PC 64 %, PTT 33 sec, fibrinogen 1.7mg/dl, Serum chemistries were generally slightly impaired except for LDH 1770 IU/L, uric acid was 6.2 mg/dl. Na 133 mmol/L, K 4.4 mmol/L, PO4 2.3 mg/dl. Her initial virology screening profile was positive for Hep A IgG and HepB sAb, while negative for rest of hepatitis B and C serologic markers and HIV. BMA was done and revealed infiltration with 70% blasts of acute myeloid leukemia (M0), immunophenotyping was done on bone marrow, blasts were positive for CD33, CD34, CD117, CD7, DR, CD11b, CD7, dim CD123 and negative for MPO, cCD3, T & B markers, & other myeloid markers tested (CD41, CD61, glycophorine A, CD14, CD64). Cytogenetic analysis by conventional karyotype showed translocation (5; 18), deletion of 12p and trisomy 19. Molecular characterization was negative for t (8,21) and inv 16 as well as for FLT3/ITD but the patient had CNS disease at presentation, that was confirmed by IPT on CSF blasts. Initial echocardiography was normal with FS% 40% and an EF% 72%.

The patient was admitted and was started on double antibiotics of cefepime and amikacin. Portacath was inseted and the patient was started on induction chemotherapy (ADE regimen: Ara-C Doxurubocin, and Etoposide) with twice weekly intrathecals.

Since start of induction, the patient was persistently febrile despite that serial blood culture and & sensitivity drawn every 48 hours: including those drawn from portacath, proved to be negative, and her CRP declined from > 200 at presentation till 78 at day 8 induction. Fever then was controlled and the patient was in quite good general condition for 5 days.

On Day 13 of induction, with secondary emergence of fever together with abdominal pain, distension and bilious vomiting, the patient was kept NPO, IV fluids were maintained with replacement of the losses and her antibiotics were shifted to meropenem and amphothericin B was added imperically. Fungal screening in the form of CT chest and abdomen was done and was normal apart from hepatosplenomegaly.

Fever and abdominal symptoms persisted for almost 1 week during which blood culture and sensitivity were drawn and CRP raised back to > 200. Finally peripheral and central blood cultures reveald staphylococcus aureus sensitive to Vancomcycin, Linezolid, clindamycin, and erythromycin and resistant to others. Vancomycin was started; fever was controlled 3 days later. 2 blood cultures were drawn to document blood clearance and the patient completed 14 days of vancomycin. At time of reevaluation, at Day 22 induction, BMA was done, was hypocellular with 1 % blasts. MRD was 0.18 %, denoting complete remission.

The patient became persistently febrile again, developed jaundice, edema, started to lose count TLC reached 300. Blood chemistries showed Bilirubin total 1.5mg/dl and direct 0.6 mg/dl were raised to 3.3mg/dl total and 1.3 mg/dl for direct bili. Mild hypoalbuminemia with albumin 2.5 g/l, PC 64 %, triglycerides: 64 ferritin: 5,600 were noted and raised the suspicion of secondary hemophagocytic lymphohistiocytosis. BMA was repeated confirmed the diagnosis and confirmed remission. The patient was started on dexamethazone. Fever was controlled for few days, blood count started to recover however abdominal symptoms were still present, repeat CT abdomen was done and was normal.

Fever redeveloped again, with positive central blood culture for staph. Aureus, portacath was removed and temporary central line was inserted instead. And the patient is continuing all through on broad spectrum antibiotics.

With full recovery of the count, the patient developed marked abdominal distension, pallor, tachycardia, hypotension and shock so she was transferred to ICU.

Urgent CXR, revealed bilateral lung infiltrates mounting to white lungs; air under the diaphragm was also noted. She was placed on mechanical ventilation and was sent to the OR for urgent surgical exploration that revealed perforated, necrotic gastric mucosa 3 tares were found. Excision and reanastomosis was done and specimens were sent to pathology.

Pathology report: The specimen consists of multiple fragments of thin membranous like tissue, green in color with focal hemorrhagic areas, measuring in aggregate 7x 7x2 cm. Microscopic examination showed non-viable necrotic muscular (stomach) wall and mesentery, with fungal organisms that are ribbon-like, wide angle, branching (confirmed by PAS, GMS). Organisms are invading the wall with evident thromboemboli. Collections of mucopurulent material with numerous neutrophils are present. Other Sections show stomach mucosa with reactive change and focal acute and chronic inflammation. Serosal surface and wall show mucopurulent inflammation and vessels show emboli of fungal organisms. Final Diagnosis: Fungal organisms morphologically compatible with mucor species, with evident angioinvasion.

The patient continued on amphothericin- B then was shifted to its liposomal form to avoid its nephrotoxic effect. She continued on antifungal therapy for more than three months. She had slow postoperative recovery, as her general condition did not permit the introduction of a second course of chemotherapy, it was held, and monthly BMA confirmed her continuous complete remission.

The patient was presented in the combined clinic, on the basis that she was in continuous complete remission for more than 4 months, that undermines the role for 2^nd course, the decision was made to place her under follow up.

1 year later, about one and half years from presentation, the patient relapsed with myeloid leukemia, for which she received another course of chemotherapy and died before confirmation of remission.

Conclusion: Immunocompromised cancer patients respond to the presence of fungal infection by vague symptoms. Many overlapping factors make the diagnosis of fungal infection difficult and delayed. The angioinvasive mucormycosis is highly aggressive with very high incidence of mortality. Early initiation of antifungal prophylaxis together with high index of suspicion are required for diagnosis. Neutropenic patients with prolonged antibiotic therapy are highly susciptible. Once diagnosed and better with clinical suspicion of angioinvasion, surgical debridement must be done hand in hand with antifungal treatment. Empiric antifungal prophylaxis is highly recommended for all AML patients.