Fever + skin rash + swollen lymph nodes, it is this kind of acute and critical illness!

Only for medical professionals to read and refer to common clinical symptoms, rare but high mortality diseases! Seeing a doctor with fever, things are not simple
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A 3-year-old child came to the emergency room .

 The chief complaint was "Fever at night for 10 days"
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 There is no specific clinical manifestation
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The indirect emergency doctors were calm and began to inquire carefully about the medical history
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 The parents complained that the child was healthy before then
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Along with fever and rash, there is also pain in the knees, ankles, and hips
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The parents denied other symptoms such as conjunctivitis, oral mucosal changes, swelling of hands and feet, rhinorrhea, coughing, difficulty breathing, abdominal pain, vomiting or diarrhea
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 "Have you been in contact with anyone with similar symptoms?" The most likely nature is an infectious disease, the doctor thought
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 "No no
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" The parents shook their heads
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 "Have you traveled recently? Have you ever gone abroad?" Ye Youshi needs to be ruled out routinely
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 "No
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" Parents waved his hand
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 "Do you have pets at home?" Allergic diseases go one
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 "Neither
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" Denied Sanlian
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In the next consultation, the parents stated that there was no family history of related symptoms and that the child had a healthy brother
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Fever + rash + swollen lymph nodes, what do you think of? Then proceed to the physical examination
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 The child is feverish, irritable, and the cervical lymph nodes are enlarged and palpable
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Swollen knees and ankles, unwilling to bear weight
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The whole abdomen is tender, and the liver and spleen are slightly enlarged
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An erythema rash can be seen on the abdominal wall, showing Koebner phenomenon
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 TipsKoebner phenomenon: Typical skin lesions are flat raised papules from rice grains to soybeans, round or oval, smooth and hard on the surface, normal skin color or light brown, and often appear suddenly, in large numbers and dense, and the skin lesions can be scratched after scratching.
Arranged in a string of beads, that is, auto-inoculation reaction or Koebner phenomenon
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The appearance of the rash is similar to the following picture: Figure 1: Erythema rash on the abdominal wall.
Fever + rash + swollen lymph nodes.
There are still three clinical symptoms with no specificity at all
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The receiving doctor touched his chin, and the n kinds of diseases that might correspond to him quickly flashed through his mind
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Auxiliary tests and inspections must be perfected to further confirm the diagnosis
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Kawasaki disease? The truth may not be so plain.
As the laboratory results are reported one by one, the cause of the child's disease seems to gradually become clear
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 White blood cells (WBC) increased, platelets (PLT) increased, complete blood count increased, hemoglobin (Hb) decreased; erythrocyte sedimentation rate (ESR) increased; C-reactive protein (CRP) increased; alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) was elevated; blood cultures, respiratory virus tests, and other infectious tests were all negative; echocardiography results were normal; abdominal ultrasound revealed liver and splenomegaly
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The clear laboratory and special examination results greatly reduce the range of possible causes
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After careful analysis, the doctor made a diagnosis of "incomplete Kawasaki disease (iKD)"
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 Tips Kawasaki disease (KD), also known as mucocutaneous lymphatic syndrome (MCLS), is a type of acute, self-limiting vasculitis that occurs mostly in infants under 5 years of age
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The clinical manifestations of KD are diverse, and some children do not have all the clinical features or the clinical features appear late, and there are certain difficulties in early diagnosis, which is called iKD
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According to the iKD part of the diagnostic criteria issued by the American Heart Association (AHA) in 2004, fever ≥ 5 days, with 2 or 3 clinical features, and CRP ≥ 30 mg/L and (or) ESR ≥ 40 mm/h, in line with the following 3 Those with laboratory indicators and above can be diagnosed: ①Albumin (ALB)≤30 g/L; ②Anemia; ③Elevated ALT; ④PLT≥450×109/L after one week of fever; ⑤Peripheral blood WBC≥15×109 /L, mainly neutrophils; ⑥Urine routine WBC≥10/HP
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 The clinical manifestations of iKD are not typical, and there are no specific laboratory diagnostic indicators.
The misdiagnosis rate is high.
It is very easy to be misdiagnosed as a common cold, leading to miss the best treatment period
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Okay, according to the above criteria, our 3-year-old child is clearly qualified for iKD diagnosis
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Hurry up and get treatment in accordance with iKD! The doctor issued a medical order and gave the child an intravenous injection of immunoglobulin (IVIG) at 2g/kg and oral aspirin
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This is the standard treatment for iKD.
IVIG improves inflammation and autoimmune response.
While aspirin is antipyretic and analgesic, it inhibits platelet aggregation and reduces the cardiovascular risk of iKD
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 Theoretically speaking, the timely and corrective treatment of iKD patients should have significant effects in a short period of time.

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However, after more than 36 hours of treatment, our child still has nocturnal fever
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 Is the dose not enough? The doctor frowned and prescribed another dose of IVIG
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 However, although the child is still in a fever, follow-up laboratory indicators found that his laboratory examination results seem to have improved, and WBC, PLT and ESR are all declining
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 Observe and see again, the doctor breathed a sigh of relief
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Suddenly, what was the cause of the disease.
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As the treatment progressed, unexpected situations appeared
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 The child’s cell counts did not stabilize after reaching normal levels
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Within 24 hours, the WBC, PLT, and Hb of the child decreased progressively, and the anemia became more and more serious
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The level of transaminase also deteriorated rapidly, with ferritin levels> 10000 ng/L
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What's more, the fibrinogen level began to decrease, and the prothrombin time and partial thrombin time began to prolong, indicating that the persistent inflammation or the unknown primary disease is affecting the coagulation function of the child
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The child became lethargic, the rash worsened, and the high fever persisted
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At this point, iKD's diagnosis seems a bit untenable
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 The doctor once again brainstormed the patient's medical history and examination data
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Persistent fever and rash, lymphadenopathy, hepatosplenomegaly, lethargy, pancytopenia, decreased ESR, liver damage, abnormal blood coagulation, and ferritin levels.
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The doctor's heavy lenses reflected the light and flashed in his mind.
There was a glimmer of light
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 Inject methylprednisolone and anakinra intravenously! Within 48 hours of starting treatment, the child's fever symptoms began to decrease, and the laboratory test results gradually improved
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After several days of treatment, the child was discharged from the hospital and went home to continue taking prednisone and anakinra
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MAS, how about a group of phenomena with stories? Are your judgments correct? The true diagnosis of this child is macrophage activation syndrome (MAS)
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 MAS is a serious and potentially fatal immune phenomenon characterized by excessive activation and proliferation of macrophages and T cells
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It is closely related to hemophagocytic lymphohistiocytosis (HLH).
The two are similar diagnoses.
HLH is often caused by genetic factors or certain malignant tumors
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MAS is usually described as a secondary HLH that often occurs in patients with underlying rheumatism
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 MAS is most common in patients with systemic juvenile idiopathic arthritis (SoJIA), but it is also associated with many other rheumatic diseases, such as systemic lupus erythematosus and KD
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 The characteristic laboratory results of MAS patients include low cell counts, decreased ESR, and fibrinogen, accompanied by liver damage, coagulopathy, and elevated ferritin levels
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The clinical manifestations are bleeding, hepatosplenomegaly, persistent fever and rash, lethargy, seizures, coma and even death
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 Fever patients with known or suspected SoJIA, ferritin level ≥684 ng/L, meet 2 of the following criteria, meet MAS: PLT≤181×109/LAST>48 U/L triglyceride>156 mg/dL Fibrinogen ≤ 360 mg/dLMAS is related to many rheumatism, but it is most closely related to SoJIA
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SoJIA, formerly known as Still disease, is an autoinflammatory disease characterized by arthritis and extra-articular manifestations, including fever, rash, lymphadenopathy, and serositis
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The typical rash of SoJIA is described as an "easy to fade orange-red rash" and presents the Koebner phenomenon
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SoJIA can occur in any age group.
In patients 18 years and older, SoJIA is also known as "adult-onset static disease"
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There are too many similar diseases in SoJIA, stupid and unclear? SoJIA needs to be differentiated from primary HLH, KD, infection and malignant tumors
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Patients diagnosed with SoJIA must have fever for at least 2 weeks and arthritis for at least 6 weeks
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However, for individuals with characteristic manifestations, a preliminary diagnosis can be made and treatment can be initiated
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MAS can occur at any point in the course of SoJIA patients.
It can occur at the initial onset, or it can be triggered during the treatment phase
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 Differentiation from primary HLH: MAS is a secondary HLH.
Compared with primary HLH, the latter patients are younger (age of onset ≤ 1.
6 years), and the reduction of neutropenia, anemia, and PLT is more obvious.
The reduction in fibrinogen levels is more pronounced, and the possibility of spleen enlargement is higher
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 Differentiation from KD: Although MAS may occur in patients with KD, as the disease progresses, clinicians should consider that the underlying diagnosis may actually be SoJIA
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Due to many common features, SoJIA and KD are usually difficult to distinguish
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Clinically, it can be distinguished by the following clues: 1.
Fever pattern: KD patients often have persistent fever, while SoJIA patients usually have night fever
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2.
Lymph nodes and liver and spleen changes: SoJIA patients usually have more extensive lymph nodes and hepatosplenomegaly and are more likely to have hepatosplenomegaly.
These two characteristics are not common in KD patients
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3.
Conjunctival and mucosal changes: Conjunctivitis and oral mucosal changes, which are diagnostic criteria for KD, are not common in SoJIA patients
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Differentiation from infectious diseases including sepsis: Acute MAS has many of the same characteristics as sepsis, and the potential source of infection must be excluded before diagnosis or treatment of MAS
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In this case, the child underwent further tests, including blood, urine and cerebrospinal fluid cultures, virological tests, bone marrow biopsy, and his infection test was negative
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 Differentiation from malignant tumors: MAS may also behave similarly to hematological malignancies
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In some cases, a bone marrow biopsy is required to rule out underlying cancer
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In this case, the blood, urine and cerebrospinal fluid examinations and bone marrow biopsy of the child did not show any signs of malignancy
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 MAS, a critical illness that cannot be underestimated! Regardless of whether the cause is SoJIA or other diseases, MAS is an acute and critical illness that must be identified and treated early to prevent serious or fatal sequelae
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The initial treatment of MAS usually includes intravenous methylprednisone pulse therapy (30 mg/kg/dose) followed by oral prednisone
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In patients who do not fully respond to steroids, the efficacy of cyclosporin A and anakinra (a recombinant interleukin-1 receptor antagonist) has been fully clinically proven
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 Etoposide is the main treatment for primary HLH, but it is not commonly used in MAS except for refractory cases
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 In this case, the child received intravenous methylprednisolone (30 mg/kg/dose) and anakinra (100 mg/day) for 3 days
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After returning home from the hospital, he continued to take prednisone and anakinra
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In the subsequent follow-up, although the child's systemic symptoms were relieved, some of his joints developed persistent arthritis during the weaning period
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So far, the child’s final diagnosis was SoJIA, which manifested as MAS, which was initially misdiagnosed as iKD
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The above is today's case sharing
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SoJIA, which is manifested as MAS, is a common clinical symptom, a rare disease with a high mortality rate.
I hope to bring some enlightenment to your clinical diagnosis and treatment~References: 1.
https://reference.
medscape.
com/viewarticle/9224152 .
Singh S, Agarwal S, Bhattad S, Gupta A, Suri D, Rawat A, et al.
Kawasaki disease in infants below 6 months: a clinical conundrum? Int J Rheum Dis.
2016;19:924–8.
3.
Zheng Jiehua.
Intravenous Efficacy of gamma globulin in the treatment of children with incomplete Kawasaki disease and typical Kawasaki disease.
Chinese Medical Science, No.
11, 2019, 204-2064.
Minoia F, Davì S, Horne A, et al.
Clinical features, treatment, and outcome of macrophage activation syndrome complicating systemic juvenile idiopathic arthritis: a multinational, multicenter study of 362 patients.
Arthritis Rheumatol.
2014;66:3160.
Source5.
Ravelli A, Minoia F, Davì S, et al.
2016 Classification criteria for macrophage activation syndrome complicating systemic juvenile idiopathic arthritis.
Ann Rheum Dis.
2016;75:481-489.
Source of this article: Pediatrics channel of the medical community Author of this article: He Shaou Editor: Cassette The medical community strives to be accurate and reliable when the content of its publication is approved, but it is not about the timeliness of the published content and the quoted materials (if any) Make any promises and guarantees for accuracy and completeness, and assume no responsibility for the outdated content and the possible inaccuracy or incompleteness of the cited information.

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