Adult-onset Still’s disease (AOSD), which was first reported in 1887 [1], is defined as a systemic inflammatory disorder of unknown aetiology and is classified as a multigene autoinflammatory disease. So far, the etiology and pathogenesis of the disease remain unclear. The levels of serum interleukin (IL)-6, IL-8, IL-18, IL-1, tumor necrosis factor (TNF), interferon (IFN), soluble IL-2 receptor and macrophage colony-stimulating factor (M-CSF) are elevated, which results in fever, rash, arthralgia and increased ferritin levels in the blood. There is a positive correlation between the serological levels of IL-18 and the degree of disease activity [2]. Clinical manifestations of AOSD include the following: ① Onset: Fever and rash are the most common symptoms of onset, and fever, rash, and arthralgia are secondary symptoms. Body temperature can drop to normal levels spontaneously by the next morning without any anti-pyretic therapy. ② Transient erythema: Erythema can occur that varies with body temperature. It may be millet-like or accompanied by scratching, usually located on the face, trunk, and limbs, and can also manifest as maculopapules. ③ Arthritis: Almost all patients have joint pain, and about 90% of patients have arthritis. If the cartilage and bone of the involved joints have erosive damage, joint stiffness and deformity may occur in the later stages of the disease. Additionally, about 80% of patients present with muscle pain. ④ Pharynx pain: most patients have pharyngeal pain in the early stages of the disease, sometimes during the whole course of the disease, but which might be reduced after a fever. Pharynx swab-culture is negative and antibiotic treatment is ineffective. Moreover, pharynx pain can be improved with the primary treatment. Others: Some patients have peripheral lymph node enlargement, hepatosplenomegaly, abdominal pain, pleurisy, etc. In rare cases there might be kidney damage, central nervous system abnormality, and peripheral nerve damage. It is additionally not uncommon for a small number of patients to be seen with acute respiratory failure and congestive heart failure, as well as disseminated intravascular coagulation (DIC). The clinical manifestations of the patient we reported were in accordance with the above-mentioned criteria defined in ① through ④ above - and these were seen in addition to splenomegaly, and pleural effusions.

(1) Routine blood tests: in the active phase of the disease, the neutrophil count is elevated in more than 90% of patients, which could be associated with orthocytochrome anemia, with almost all patients presenting with a rapid increase in ESR. (2) The liver enzyme levels i.e., Alanine aminotransferase (ALT), and Aspartate aminotransferase (AST) increase slightly in some patients, especially in cases of fever. (3) Blood bacteria culture is negative. (4) Rheumatoid factor (RF) and antinuclear antibody (ANA) are negative, and only a few individuals show a slightly positive outcome with normal or high complement levels. (5) The level of serum ferritin (SF) is also significantly elevated, which is helpful for differential diagnosis. We found that the level of SF was positively correlated with the activity of the disease. (6) The leukocytes in the hydrothorax show inflammatory changes, in which neutrophils are increased predominantly. (7) The ESR is shown to increase. (8) Bone marrow examination shows infectious foci.

AOSD is a diagnosis of exclusion; however, there is no uniform diagnostic standard. At present, the Yamaguchi criteria are widely used [3]. The main indices of these criteria include the following: (1) Temperature at or above 39 ℃ that lasts for more than 1 week; (2) arthralgia that lasts for more than 2 weeks; (3) typical skin rash; and (4) WBC counts of up to or above 10.0 × 10${}^9$/L, including neutrophil counts of up to or above 0.80. Secondary indices include the following: (1) pharyngalgia; (2) lymph node enlargement and/or splenomegaly; (3) abnormal liver function; and (4) negative rheumatoid factor (RF) and antinuclear antibody (ANA) levels. The above indicators can be diagnosed as AOSD when more than five items are present (two or more of the main indicators are required), excluding infectious diseases (especially septicemia and infectious mononucleosis), malignant tumors (especially malignant lymphoma and leukemia) and other rheumatic diseases (especially multiple aneurysms, rheumatic vasculitis of extraganglial signs). Although the level of SF is associated with disease activity, it has not yet been included in the diagnostic criteria. On the basis of adding the Yamaguchi criteria and serum ferritin (i.e., levels above 1250 ug/L) as conditions for the diagnosis of AOSD, its specificity increases from 92.1% to 99.2% [4].

At present, treatments are divided into drug therapy and surgical treatment.

(1) Drug therapy: there is no radical cure for AOSD. Drug therapy can improve clinical symptoms; commonly used agents include non-steroidal anti-inflammatory drugs, glucocorticoids, anti-rheumatics such as methotrexate, gold preparations, azathioprim, and cyclosporine A. Still controversial are the use of some Chinese herbal preparations, and the use of intravenous injection of gamma globulins. Plasma exchange is also a treatment option for AOSD. In recent years, it has been reported that antagonists of IL-1, IL-6 and TNF-$\alpha$ have been used in the treatment of these patients. Reports suggest that the clinical symptoms of the patients can be relieved rapidly [5].

(2) Surgical treatment: patients with arthritis as the main manifestation should have regular X-rays taken of the involved joints. With joint erosion, destruction or deformity, the patients need to consider arthroplasty in the case of extensive joint damage, but is often prevented by early intervention with immune modulating medications.

Limited studies have shown that when AOSD presents in pregnancy, the onset is most likely to occur in the mid-trimester of pregnancy, next in early pregnancy, and even less likely post-partum. The risk of pregnancy complications and adverse pregnancy outcomes in patients with AOSD in relative remission are lower than those found in those patients without effective control of the disease. To some extent, AOSD affects pregnancy outcomes; the adverse outcomes of pregnancy include including preterm labor, fetal growth restriction (FGR), premature rupture of membranes, oligohydramnios, and preeclampsia [6]. However, based on few studies and case reports, little is actually known about the pregnancy outcome and neonatal outcome of AOSD patients with pregnancy, especially the impact of different medications during pregnancy on them. In particular, Anna Lin et al. [7] reported case of neonatal hemophagocytic syndrome associated with maternal AOSD for the first time in 2016. The infant they reported was seemingly normal apart from mild prematurity at birth. Later, the infant showed symptoms including high fever, hepatosplenomegaly, cytopenia, marked hyperferritinaemia, hypofibrinogenaemia, and fulfilled the diagnostic criteria of hemophagocytic syndrome. The author pointed out that the infants present with clinical features mimicking severe sepsis or pneumonia typically. However, they have negative microbial cultures and are unresponsive to anti-microbial agents. Although the exact mechanism cannot be fully elucidated, it is likely that the infants acquired secondary hemophagocytic syndrome via vertical transmission of factors from her mother with AOSD. Researchers thought that neonatologists should be reminded of the possibility of hemophagocytic syndrome for newborns with family history, symptoms such as fever, hepatosplenomegaly and cytopenia and no response to antimicrobial drugs. Isolation, prevention and corticosteroid treatment and chemotherapy are important treatment options [7].

Different patients show diversity and heterogeneity in the course of the disease. Most patients are prone to recurrent attacks after remission, and a few do not relapse after a single remission and have a tendency of self-limitation. Some patients exhibit the chronic persistent-activity type, which eventually appears as a chronic arthritis with accompanying cartilage and bone destruction similar to that seen in rheumatoid arthritis.

As described in the initial 1982 case report, AOSD can be triggered by pregnancy. We collected 31 cases of AOSD during pregnancy (Table 1), involving women aged 19–40 years (Median age = 28.5), with the majority of pregnant patients with AOSD occurring at 8 to 26 weeks of gestation and during the postnatal period. However, the case at our hospital was diagnosed for the first time at 33 weeks of gestation. In terms of symptoms and laboratory tests, the main manifestations were arthritis, arthromyalgia, fever, and pharyngitis, among other observations. The serum ferritin level was between 1311 and 40000 ng/mL. There may be some increased risk for adverse pregnancy outcomes, as shown in these few studies; the patient in the present report eventually gave birth prematurely. Of the 31 cases mentioned above, there were 11 cases of premature labor, 3 cases of premature rupture of the membranes, 6 cases of intrauterine fetal growth restriction, 2 cases of oligohydramnios, 1 case of neonatal death and 1 case of abortion. Of the 11 cases of premature labor, 10 were treated with steroids during pregnancy. The patient admitted to our hospital was also treated with steroids during pregnancy and delivered a premature baby at 36 weeks of pregnancy. The relationship between the occurrence of complications and the specific pathology of AOSD is unclear; it might be associated with steroid therapy and side-effect manifestations. However, recent studies have shown that high levels of IL-18 during pregnancy might provoke onset of potential diseases, leading to the occurrence of AOSD [20]. In terms of treatment regimen, most of the patients received hormonal therapy, two of them were treated with intravenous immunoglobulin, and there was no significant difference between monocyclic and polycyclic outcome [26]. In the future, AOSD pathophysiology and the application of targeted therapy may benefit patients and obtain a remarkable curative effect [23]. As mentioned earlier in the article, hemophagocytic syndrome may also be one of the manifestations of adverse neonatal outcomes. As we reported in this case, the neonates delivered by pregnant women with AOSD should be alert to the occurrence of hemophagocytic syndrome.

In conclusion, the diagnostic criteria of pregnancy complicated by AOSD remain unclear, and mainly depend on a diagnosis of exclusion. Due to a diverse clinical manifestation of AOSD, there is a high rate of clinical misdiagnosis. The literature both at home and abroad shows that the onset of AOSD is closely related to pregnancy, and that pregnancy is one of its predisposing factors. Its clinical manifestations are arthritis, arthromyalgia, fever, pharyngitis and so on, which involve multiple systems. There is no highly specific approach available in the laboratory examination and imaging for this disease. AOSD is a group of rare clinical syndromes, and at present, very little is known about the mechanism relating pregnancy to AOSD.

Finally, the prognosis for the pregnant woman and her fetus, as well as adequate follow-up of the pregnancy and post-natal period, collectively, present us with a great deal of uncertainty. A significant program of published clinical and basic research are still needed in order to reduce this uncertainty and strengthen a more specific differential diagnosis in the future.