Case Reports in Hematology of antiretroviral l therapy (ART) during the last decade of the twentieth century, according to a large multisite US HIV-infected outpatient cohort, IRIS occurred in 10.6% of patients who responded to eﬀective ART and contributed to increased mortality [2]. In another study, Shelburne et al. found the incidence of IRIS of any type to be 32% in patients during ART [3]. IRIS is also observed in non-HIV immunocompromised patients as solid organ transplantation recipients, postpar- tum period, tumor necrosis factor (TNF) antagonist recipi- ents, and as in our case hosts during neutrophil recovery after chemotherapy [4]. Risk factors for IRIS in HIV patients include low CD4 and high viral load at the time of eﬀective ART initiation or resumption [2], duration of immunodeﬁciency, velocity and extent of immune recovery, and genetic susceptibility (distinct HLA types and polymorphisms in cytokine genes) [5]. Patients with hematological malignancies after high- dose chemotherapy develop immune reconstitution due to recovery of the innate immunity [6], the most crucial risk factor for IRIS in this category is the velocity of recovery of neutrophil count [7], the latter one was clearly observed in our patient as his ANC increased 10-folds within four days (from 1100 cell/µL on day 18 to 11,500 cell/µL on day 22 post chemotherapy), and GCSF was only discontinued when it reached 8,000 cell/µL. This demonstrates the importance to understand the balance between GCSF beneﬁts to restore immunity versus the potential harm in developing IRIS during neutrophil recovery. 2.3. Clinical Manifestation. Presentation of IRIS usually correlates with the organ involved by the opportunistic infec- tion; manifestations include fever, skin nodules, ocular lesions, bone and joint involvement, liver lesions, bladder lesions, and lung inﬁltrates. Pulmonary IRIS in particular was thoroughly described, especially in the setting of TB infection, symptoms can range from cough, wheezes, worsening chest X-ray to respiratory failure [8, 9], and acute respiratory distress syndrome [10, 11]. IRIS presenting as ARDS was ﬁrst reported by Goldsack et al. [10] in an HIV patient with pulmonary tuberculosis. Wikman et al. [11] described a non-HIV patient who suﬀered from ARDS as a manifestation of IRIS secondary to pulmonary TB; in our patient, ARDS was a systemic manifes- tation of IRIS secondary to streptococcus viridans septicemia rather than an exaggerated response against a pulmonary in- fection. In patients recovering from neutropenia, IRIS tends to happen up to 15 days after the resolution neutropenia (mean of 2 days) [8]; in our patient, the clinical and radiological deteriorations were noticed on the ﬁrst day of neutropenia resolution, whereas HIV-associated IRIS appears to develop 8–150 days (mean of 33 days) after starting ART [12]. 2.4. Diagnosis. Diagnosis of IRIS is not straightforward as there are no universal clinical criteria or diagnostic tests to conﬁrm it. In our case, we initially attributed the ARDS to 3 sepsis but when we noticed the initial relative response, the strong temporal relationship between deterioration and the neutrophil recovery, the negative BAL culture, and repeatedly negative blood cultures, we decided to make the diagnosis. Clinical deterioration in similar cases can also be due to progression of the current opportunistic infection, failure of therapy, a new infection, or drug interaction. Diﬀerent studies provided a number of diﬀerent clinical criteria to help diagnose IRIS. In general, these criteria include the following [8]: (1) temporal association between neutrophil recovery and clinical deterioration; (2) robust microbiologic response (no evidence of wors- ening infection); (3) subsequent resolution without antimicrobial modiﬁ- cation; (4) improved outcome after immunomodulation using medications like steroids. Whether ARDS in our patient was solely caused by IRIS or the combined eﬀect of septic shock and IRIS might never be known. 2.5. Management. Treatment of IRIS in the setting of recov- ery from neutropenia is diﬃcult as it largely depends on case reports, even in HIV-associated IRIS, there is only one randomized placebo-controlled trial of prednisone for the treatment of paradoxical TB-IRIS [13]. In this trial which included 110 participants, Meintjes et al. found signiﬁcant improvement in symptoms and quality of life in patients who received prednisone compared to those who received placebo, and it is interesting that the timeline for chest X- ray improvement was 2–4 weeks exactly like our patient. Prednisone dose was 1.5 mg/kg/day for two weeks followed by half the dose for another two weeks. As was seen in our patient, it is also important to withdraw GCSF when IRIS is suspected. 3. Conclusion Immune reconstitution inﬂammatory syndrome is associ- ated with increased morbidity and mortality; it can be a medical mystery as it depends largely on high suspicion and ruling out other etiologies. A consensus about clinical criteria or a diagnostic laboratory test is needed to help diagnosing this disease, and more randomized controlled trials are needed to conﬁrm the role of steroids. References [1] S. T. Chambers, W. A. Hendrickse, and C. Record, “Paradoxi- cal expansion of intracranial tuberculomas during chemother- apy,” The Lancet, vol. 2, no. 8396, pp. 181–183, 1984. [2] R. M. Novak, J. T. Richardson, K. Buchacz et al., “Immune reconstitution inﬂammatory syndrome: Incidence and impli- cations for mortality,” AIDS, vol. 26, no. 6, pp. 721–730, 2012. [3] S. A. Shelburne, F. Visnegarwala, J. Darcourt et al., “Incidence and risk factors for immune reconstitution inﬂammatory