What is the real culprit behind the severe headache?

*For medical professionals' reference only, read excellent case analysis Idiopathic hypereosinophilic syndrome (IHES) is a group of unexplained persistent hyperplasia of eosinophils accompanied by multiple organ damage.

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Clinically, IHES is rare
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Then it is even rarer to have cryptococcal eosinophilic meningitis after its treatment.
Let's look at the case together! Medical records male, 54 years old, the main reason for this hospitalization was "headache for 1 month, aggravation for 5 days", no special personal and family history
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▌ History of present illness: 2019-1-24: due to chest tightness, shortness of breath for 1 month, and leukocyte elevation for 8 days, he was hospitalized in the hematology department of our hospital.
The highest absolute EO count was 24.
93 X109/L.
After intravenous injection of methylprednisolone 80 mg, 1/day, after 2 consecutive days, the white blood cells decreased to 17.
16 X109/L, the EO ratio decreased to 20.
90%, and the EO absolute count decreased to 3.
58.
X109/L
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Discharge diagnosis: IHES
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2020-10-30: Due to intermittent chest tightness and shortness of breath for more than 1 year, the chest pain aggravated for 1 day and was diagnosed as acute extensive anterior myocardial infarction in the Department of Cardiology of our hospital.
93.
64X109/L, the highest EO ratio was 83.
80%, and the highest absolute EO count was 78.
49X109/L.
After intravenous injection of methylprednisolone 80mg, combined with hydroxyurea 0.
5g, 3/day, after 13 consecutive days, the white blood cells decreased to 33.
12X109/L, EO ratio dropped to 26.
80%, EO absolute count dropped to 25.
42X109/L
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The discharge diagnosis was: IHES.
After discharge, oral imatinib and cyclophosphamide were continued
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2021-9-24: Due to headache for 1 month, aggravated for 5 days in the neurology department of our hospital
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The patient developed severe headache one month ago, and developed fever half a month ago, with a body temperature of up to 38.
5°C.
The fever subsided after symptomatic treatment in the local hospital
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5 days ago when I was working, the headache was aggravated, and it was on the back of my neck
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After analgesic treatment, the pain was not relieved, accompanied by nausea and vomiting, so he came to our department for treatment
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▌ The physical examination on admission was uncooperative, the muscle strength and muscle tone of the limbs were normal, and the deep and superficial reflexes of the bilateral limbs were elicited normally
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Feeling, lack of cooperation
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The neck was rigid, the distance between the chin and the sternum was 4 cm, and both Kernig's and Brudzinski's signs were positive
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The pain score is 10 points
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▌ Auxiliary examination of head MRA showed changes in cerebral atherosclerosis
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Brain CT showed no obvious abnormality, and brain MRI and enhanced scan + DWI + SWI + MRV showed no abnormality
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Blood routine: WBC 20.
37×109/L, EO ratio 25.
1%, EO absolute count 5.
11×109/L, C-reactive protein concentration 42.
78 mg/L
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The results of fungal D-glucan test and Aspergillus immune test were normal
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On the fourth day of hospitalization, a lumbar puncture was performed, and the cerebrospinal fluid was transparent and colorless
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The results of the CSF analysis are shown in the following table: Table 1 The CSF report is shown in Figure 1 (AB), and the cerebrospinal fluid ink staining (see Figure 1C) shows Cryptococcal infection
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Figure 1 Bacterial culture: infected with Cryptococcus neoformans, sensitive to flucytosine, amphotericin B (AmB), fluconazole, itraconazole, and voriconazole
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Second-generation sequencing of cerebrospinal fluid: presence of Cryptococcus neoformans complex group, no mycobacteria
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Gram staining, acid-fast staining and cerebrospinal fluid pathological smear analysis showed no abnormal results
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According to the medical history and auxiliary examination results, the patient was diagnosed as cryptococcal meningitis (CM) combined with eosinophilic meningitis (EM)
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During the treatment and follow-up treatment, intravenous fluconazole 800 mg, intrathecal injection of AmB 0.
2 mg antifungal therapy, and intravenous injection of mannitol 30 g q6h were given to reduce intracranial pressure
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After drug treatment, the patient's headache improved significantly
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Following the opinions of the patient and his family, he was transferred to a specialized hospital for further treatment on September 28, 2021, and received AmB and voriconazole for 5 weeks, and was discharged from the specialized hospital on November 2, 2021
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Although EO has disappeared in the cerebrospinal fluid, a small amount of Cryptococcus still exists
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At follow-up in January 2022, the patient reported that the headaches were still intermittent
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Discussion Because this patient suffers from IHES, long-term oral immunosuppressive agents after discharge from the hospital are prone to opportunistic infections.
According to the results of cerebrospinal fluid test, the patient was diagnosed with CM combined with EM.
After antifungal treatment, the headache was relieved, CM improved, EM was cured, and CM developed after IHES.
Cases with EM have not yet been reported
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Therefore, it is considered that the patient's EM is caused by Cryptococcus infection, and CM is the most common fungal infection in the central nervous system, which is caused by Cryptococcus neoformans infection
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▌ Mechanism Cryptococcus neoformans is widely distributed in nature and is an opportunistic pathogen that causes disease when the host immunity is low
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Cryptococcus neoformans central nervous system infection can occur in isolation, but is more common in diseases such as human immunodeficiency virus (HIV), lymphoma, and hematological disorders, such as the presence of IHES in patients
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Initially, it often infects the skin and mucous membranes and invades the human body through the upper respiratory tract
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▌ Clinical manifestations (1) Fever, progressive headache, mental and neurological symptoms (confusion, irritability, disorientation, behavior changes, lethargy, etc.
); (2) Intracranial hypertension is often more obvious, headache, nausea and vomiting are more obvious Severe; (3) The progression of the disease may involve cranial nerves (oculomotor nerve, abducens nerve, optic nerve, etc.
), and cranial nerve palsy (manifested as hearing abnormalities or deafness, re-examination, limited eye abduction, etc.
) and papilledema, Brain parenchymal involvement may present clinical manifestations such as motor, sensory disturbance, brain dysfunction, seizures, and dementia
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▌ Auxiliary examination (1) Cerebrospinal fluid examination: pressure often increases, lymphocyte count increases, protein content increases, sugar content decreases, and the detection of Cryptococcus by ink staining can confirm the diagnosis; (2) head CT and MRI can help diagnose hydrocephalus, Chest X-ray may have pneumonia-like and lung space-occupying changes
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▌ Treatment 1.
Mannitol lowers intracranial pressure and corrects water and electrolyte imbalances; 2.
Antifungal therapy: IDSA recommends AmB (0.
7-1.
0 mg·kg-1) as the first choice for induction in the 2010 revised guidelines for the treatment of cryptococcosis [1].
·d-1) Combined with flucytosine (100mg·kg-1·d-1), the course of treatment was 4 weeks, and after entering the consolidation phase, fluconazole (600-800mg/d) was used
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If the renal function is normal, the recommended dose of fluconazole is 800 mg/d.
Studies have shown that [2] for non-HIV/AIDS-related CM, high-dose fluconazole (600-800 mg/d) has better efficacy, and can be combined with flucytosine (100mg·kg-1·d-1 is taken in 4 divided doses); for patients with renal insufficiency, the recommended dose of fluconazole is 400mg/d
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In addition, in 2016, the German Society of Hematology recommended in the guidelines for central nervous system infections [3] that AmB lipid preparations are the first choice for the treatment of hematological diseases complicated by CM, mainly due to the large adverse reactions of AmB in patients with blood diseases, but domestic clinical studies have shown that Low-dose AmB is well tolerated, so AmB is still recommended as the first choice, and adverse reactions should be closely monitored
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▌ Prognosis The disease is often aggravated progressively, with poor prognosis and high mortality rate.
Complications and neurological sequelae are also common in the treatment, and the condition is repeatedly relieved and aggravated within a few years
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Summary: In conclusion, IHES is a heterogeneous group of diseases with atypical symptoms and signs, and the diagnosis is mainly based on exclusion
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At the same time, tissue and organ damage caused by pathogenic mechanisms such as thrombosis cannot be ignored
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References: [1] Zhou Yingjie, Li Guanghui, Perfect JR, et al.
Clinical practice guidelines for the management of cryptococcosis: 2010 update of the American Society of Infectious Diseases [J].
Chinese Journal of Infection and Chemotherapy, 2010, 10(03): 161- 166.
[2]Iyer KR,Revie NM,Fu C,et al.
Treatment strategies for cryptococcal infection:challenges,advances and future outlook[J].
Nat Rev Microbiol,2021,19(7):454-466.
[3 ]Maziarz EK,Perfect J R.
Cryptococcosis[J].
Infect Dis Clin North Am,2016,30(1):179-206.