Several reports of adult-onset immunodeficiency syndrome have been associated with anti-interferon-gamma (IFN-γ) autoantibodies (AIGAs). However, it is rare to find AIGAs with intracranial infections.

In this case study, we report a case of an AIGAs with intracranial infection and hand rashes considered Sweet’s syndrome. The patient presented to our hospital with a persistent cough, a fever that had been going on for 6 mo, and a rash that had been going on for a week. The patient started losing consciousness gradually on the fourth day after admission, with neck stiffness and weakened limb muscles. The upper lobe of the left lung had a high-density mass with no atypia and a few inflammatory cells in the interstitium. Brain magnetic resonance imaging and cerebrospinal fluid suggest intracranial infection. The pathology of the skin damage on the right upper extremity revealed an infectious lesion that was susceptible to Sweet’s disease. It has an anti-IFN-γ autoantibody titer of 1:2500. She was given empirical anti-non-tuberculous mycobacterial and antifungal treatments. The patient had no fever, obvious cough, headache, or rash on the hand. She got out of bed and took care of herself following hospitalization and discharge with medicine.

Adults with severe and recurrent infections of several organs should be considered for AIGAs if no other known risk factors exist. AIGAs are susceptible to subsequent intracranial infections and Sweet’s syndrome.

Adult-onset immunodeficiency syndrome associated with anti-interferon-gamma (IFN-γ) autoantibodies (AIGAs) has been discovered in Southeast Asia, including Thailand, Vietnamese, Japan, the Hong Kong Special Administrative Region of China, and Taiwan, since it was first reported in the Philippines in 2004[1-7].

The strong correlation between high-titer neutralizing antibodies to IFN-γ and this adult-onset immunodeficiency syndrome supports the critical function of IFN-γ in controlling many pathogens. Autoantibodies against IFN-γ have been linked to opportunistic infections, most frequently non-tuberculous mycobacterial (NTM) infections, and others, and can lead to immunodeficiency[1,8,9]. Thus, AIGAs may be viewed as a new form of late-onset immunodeficiency that confers a predisposition to some bacterial and fungal infections and severe mycobacterial illnesses.

Most patients have multiple organ involvement upon presentation; lymph nodes are the most often affected organ, followed by the skin, lungs, bones, blood, and joints[10]. The non-specific symptoms and rarity of this syndrome make it challenging to identify in the early stages of the disease. According to reports, 49%-57% of AIGAs had skin manifestations[11,12]. The skin manifestation of adult-onset immunodeficiency syndrome, known as Sweet’s syndrome, is frequently associated with AIGAs[13]. Acute febrile neutrophilic dermatosis, another name for Sweet’s syndrome, is a rare inflammatory condition. Its symptoms are acute onset dermal neutrophilic lesions, leukocytosis, and pyrexia. Sweet’s syndrome frequently appears as erythematous plaques and nodules and is most commonly seen in reactive dermatitis. We have reported a patient with intracranial infection accompanied by hand rashes who also had IFN-γ autoantibodies, a condition known as Sweet's syndrome.

AIGAs with intracranial infection and Sweet’s syndrome was the final diagnosis.

Ceftriaxone (1000 mg bid), amikacin (600 mg qd), azithromycin (500 mg b.i.d.), rifampicin (600 mg q.d.), ethambutol (1000 mg q.d.), and fluconazole (200 mg qd).

The patient had no fever, no obvious cough, no rash on the hand, and no headache after spending 20 d in the hospital before being discharged with medicine. The patient could get out of bed and care for herself because she was conscious. When she was seen again at the hospital two months later, all the signs were better than they had been. The patient continued receiving anti-mycobacterium therapy during future outpatient visits.

When a patient has multiple organ infections, typically from opportunistic infections without known immunosuppression, the diagnosis of adult-onset immunodeficiency syndrome associated with AIGAs should be considered. Since tests for established immunodeficiencies like human immunodeficiency virus are negative and antibodies to IFN-γ are strongly positive in this case, we gave the diagnosis of AIGAs some thought. Opportunistic infections, most frequently NTM infections and others, are linked to AIGAs[1-7]. Adult-onset immunodeficiency and NTM infection also showed a favorable additive interaction trend. We emphasize that even when culture results are negative, clinicians should be on the lookout for NTM infection in patients with AIGAs. Anti-IFN-γ was increased despite the lack of a confirmed NTM infection, and empirical anti-NTM treatment was successful in this case.

AIGAs damage multiple organs[10]. The lymphadenopathy, lungs, skin, and brain are the primary organs affected by this situation. CSF and brain MRI findings in this case led to the hypothesis of intracranial infection. Breakdown of the blood-brain barrier (BBB) is a common feature of many diseases of the central nervous system (CNS), including encephalitis. When the BBB is compromised in CNS diseases, there is a reduction in the transport of nutrients/oxygen, a quick influx of immune cells, and brain swelling that can exacerbate brain damage. According to a report, IFN-γ causes BBB leakage. In brain endothelial cells exposed to disease tissue lysate, IFN-γ is a barrier disruptor[14]. Through Rho kinase-mediated cytoskeletal contractions, IFN-γ reduces barrier properties in cultured brain endothelial cells, leading to junctional instability and cell-cell separations. We decided to use a medication that may penetrate the BBB to treat the intracranial infection present in this case.

In this instance, there was also skin damage. Skin pathologic or dermatologic examination findings supported the existence of Sweet’s syndrome. Neutrophilic dermatoses with negative microbial cultures were found by histopathology. Sweet’s syndrome is associated with adult-onset immunodeficiency, which includes lymphadenopathy, pustular lesions, and leukocytosis[15]. Clinicians should be aware of the possibility of an underlying adult-onset immunodeficiency since patients with Sweet’s syndrome have a specific clinical presentation that includes lymphadenopathy, pustular lesions, and leukocytosis.

In adults with severe and recurrent infections of multiple organs without other recognized risk factors, AIGAs should be considered. In AIGAs syndrome, the BBB may break down, leading to an intracranial infection. Sweet’s syndrome usually coexists with this syndrome.