Gallstone disease in children: diagnosis and treatment

Gallstone disease in children is the formation of stones in the gallbladder and/or bile ducts, manifested by pain in the right hypochondrium, dyspepsia, obstructive jaundice, or acute pancreatitis. In recent years, the disease has been diagnosed more frequently, which is associated with rising obesity rates, the widespread use of certain medications, and improvements in ultrasound diagnostics. [1]

In terms of composition, pediatric stones are more often pigmented (due to hemolysis) or mixed, less often pure cholesterol, as in adults. Ultrasound of the abdominal cavity plays a key role in initial detection, while clarification of ductal lesions requires magnetic resonance cholangiopancreatography and, if necessary, therapeutic and diagnostic endoscopy. [2]

Management tactics vary from observation in asymptomatic cases to laparoscopic cholecystectomy in cases of pain or complications, and for common bile duct stones, from endoscopic papillosphincterotomy with stone extraction to laparoscopic removal of duct stones during surgery. The choice of strategy is based on standardized risk stratification. [3]

The most significant risk factors in children include sickle cell hemolytic anemia, hereditary spherocytosis, obesity, parenteral nutrition, ceftriaxone use, ileal diseases, and cystic fibrosis. Identifying the underlying factors determines relapse prevention and surgical indications. [4]

Code according to ICD-10 and ICD-11

In ICD-10, cholelithiasis is coded under class K80, specifying the location and complications. For example, K80.2 is for gallstones without cholecystitis, K80.5 is for bile duct stones without cholangitis, and K80.0 is for gallstones with acute cholecystitis. Correct coding is important for routing and selecting treatment strategies. [5]

In ICD-11, biliary tract stones are classified under DD93, detailing complications and localization, while acute infectious complications (cholecystitis and cholangitis) have separate codes. The transition to ICD-11 requires recording the presence of pancreatitis, cholestasis, and infection, as this changes the code and clinical guidelines. [6]

Table 1. Code examples

Clinical situation	ICD-10	ICD-11
Gallstones without cholecystitis	K80.2	DD93.00
Bile duct stones without cholangitis	K80.5	DD93.10
Acute calculous cholecystitis	K80.0	DD93.01
Gallstone pancreatitis	K85.1	DC40.3 with reference to the bile source

Epidemiology

The prevalence of gallstone disease in the pediatric population varies by region and age, typically remaining below 1%; however, rates increase during adolescence, particularly in the context of obesity and metabolic factors. The availability of ultrasound leads to a more frequent detection of asymptomatic forms. [7]

Children with obesity have a significantly higher risk of developing stones than their peers with normal body weight: according to modern observational data, the proportion of overweight and obesity among children with stone disease reaches 36% and 12%, respectively, which is significantly higher than control values. [8]

Certain cohorts demonstrate a high incidence of stones in hemolytic conditions: in children with sickle cell disease, the incidence of cholelithiasis can exceed 10% and increases with age, due to chronic hemolysis and pigment stone formation. This justifies early screening with ultrasound. [9]

The importance of drug-induced stones is also growing, especially with the use of ceftriaxone: cases of biliary sludge and stones in the gallbladder and common bile duct have been reported in children after a course of therapy, with the risk increasing with dose and duration. Most episodes are reversible upon discontinuation of the drug. [10]

Table 2. Epidemiological landmarks

Group	Risk or frequency assessment
General child population	usually <1%, higher in adolescence
Obesity	significant increase in risk compared to control
Sickle cell disease	double-digit percentages by the teens
Ceftriaxone therapy	transient sludge and stones in some patients

Reasons

In children, the causes of cholelithiasis are heterogeneous: hemolysis with increased formation of unconjugated bilirubin, dyskinesia associated with obesity and insulin resistance, inflammatory or resection lesions of the terminal ileum, prolonged parenteral nutrition, and drug effects. Understanding the etiology determines prevention and management. [11]

Ceftriaxone can form insoluble complexes with calcium in bile, causing sludge and stones in children, especially at high doses and over long periods. Discontinuation of the drug often leads to resolution of the findings, but if stones migrate into the bile ducts, intervention may be required. [12]

Obesity is associated with lithogenic bile, increased cholesterol saturation, and bladder hypomotility, which promote crystal precipitation and stone growth. Weight loss and dietary modification reduce the risk of recurrence after treatment. [13]

In hemolytic anemias, chronic hemolysis increases the bilirubin load, forming pigment stones even in young children. In these cohorts, the threshold for surgical treatment is lower due to the high rate of complications and relapses. [14]

Risk factors

Modifiable factors include obesity, physical inactivity, a high-calorie diet with excess saturated fat, long-term use of certain medications, and long-term parenteral nutrition. Their correction is the basis of primary and secondary prevention. [15]

Non-modifiable factors include hereditary hemolytic diseases, cystic fibrosis, congenital biliary tract anomalies, and terminal ileal diseases. In these groups, regular ultrasound examinations and early surgical consultation are indicated if symptoms develop.[16]

Medication-related factors include ceftriaxone and some hormonal medications in adolescents. If alternatives are available and there is a high risk of stone formation, other regimens are preferable, especially for long-term treatments. [17]

In children with sickle cell disease and hereditary spherocytosis, the risk of stones and complications is high, so even asymptomatic stones may be considered as an indication for elective cholecystectomy to prevent attacks and pancreatitis. The decision is made individually by a multidisciplinary team. [18]

Pathogenesis

Common mechanisms include bile supersaturation with cholesterol or bilirubin, gallbladder hypomotility, and crystal nucleation against a background of sludge. An imbalance between solubilization and precipitation promotes stone growth and migration into the ducts. [19]

In hemolysis, excess unconjugated bilirubin leads to the formation of calcium bilirubin pigment stones. These stones are prone to recurrence and migration, increasing the risk of choledocholithiasis and pancreatitis in children. [20]

Obesity increases cholesterol synthesis and reduces bile acid fraction, which increases bile lithogenicity; concurrently, gallbladder hypomotility increases crystallization time. Hormonal influences are added during adolescence. [21]

Ceftriaxone forms complex salts with calcium, which precipitate in bile and form sludge, which can serve as a matrix for stones; after discontinuation of the drug, the sludge usually resolves, but not always until the stones disappear. [22]

Symptoms

A classic attack of biliary pain is characterized by intense, progressive, and persistent pain in the right hypochondrium or epigastrium lasting more than 30 minutes, often accompanied by nausea and vomiting; the pain is not associated with defecation. In infants, the symptoms may be atypical and disguised as "colic." [23]

Choledocholithiasis is accompanied by jaundice, dark urine, acholic stools, and itching; signs of cholangitis, including fever, chills, and severe pain, are also possible. In some patients, the first manifestation is acute pancreatitis with severe pain and elevated amylase and lipase. [24]

Interictal complaints include heaviness after fatty foods, flatulence, unstable stool, and, in schoolchildren, decreased exercise tolerance due to recurring pain. Asymptomatic stones are often detected incidentally on ultrasound. [25]

In patients at risk for hemolysis, cystic fibrosis, and bowel disease, symptoms often debut as complications, which dictates a low threshold for referral to a surgeon and more active monitoring. [26]

Classification, forms and stages

Based on location, cholelithiasis is classified as gallstones, choledocholithiasis as common bile duct stones, and combined forms. Symptoms, risk of complications, and treatment strategies depend on location. [27]

Based on the clinical course, the disease is classified as asymptomatic, symptomatic uncomplicated, and complicated: acute calculous cholecystitis, cholangitis, and gallstone pancreatitis. This classification is important for determining the timing and extent of intervention. [28]

Stones are classified by composition: pigment, cholesterol, and mixed; in pediatrics, pigment stones predominate in hemolytic patients and mixed stones in adolescents with metabolic factors. This influences the effectiveness of dissolution therapy. [29]

According to the risk of intervention, patients are stratified into low, intermediate and high risk of choledocholithiasis based on clinical, laboratory and ultrasound features, which determines the sequence of imaging and the need for endoscopy. [30]

Complications and consequences

The most common complications are acute calculous cholecystitis, choledocholithiasis, acute biliary pancreatitis, and cholangitis. In children with hemolysis, complications occur more frequently and at an earlier age. [31]

Recurrent pain and hospitalizations impair quality of life, while missed school days and physical limitations impact the development of the child and family. Timely surgery, when indicated, reduces the burden of disease. [32]

Cholangitis carries a risk of systemic infection and requires urgent duct decompression and antibacterial therapy; delay leads to sepsis and multiple organ failure. Early recognition of warning signs is crucial. [33]

Gallstone pancreatitis in children requires coordination between a gastroenterologist, surgeon, and endoscopist; incorrect sequencing of interventions increases the risk of recurrence and complications, which justifies following clinical routes. [34]

When to see a doctor

Seek immediate medical attention if you experience severe pain in the right upper quadrant for more than 30 minutes, repeated vomiting, fever, yellowing of the skin or sclera, severe itching, acholic stools, or dark urine. These are signs of possible bile duct obstruction and infection. [35]

A routine consultation is required in cases of recurrent attacks of pain after fatty foods, episodes of transient jaundice, in families with hemolytic diseases, as well as in cases of stones detected by ultrasound - to assess the risk and discuss prevention. [36]

Children with sickle cell disease, hereditary spherocytosis, and cystic fibrosis are recommended to have regular ultrasound monitoring and early surgical consultation with any symptoms. [37]

After courses of ceftriaxone, if pain or discomfort in the right hypochondrium occurs, an assessment of the biliary system is indicated, since drug sludge can be complicated by migration into the ducts. [38]

Diagnostics

Initial evaluation includes clinical examination, complete blood count and biochemistry with liver function profile (bilirubin, alkaline phosphatase, gamma-glutamyl transferase, amylase and lipase), and abdominal ultrasound as a first-line test to detect stones and signs of cholecystitis.[39]

If stones in the common bile duct are suspected, magnetic resonance cholangiopancreatography is used as a non-invasive clarifying method; if there is a high probability of obstruction and clinical features of cholangitis, therapeutic and diagnostic endoscopy is performed to remove stones. [40]

Choledocholithiasis risk stratification is based on symptoms, laboratory parameters, and ultrasound signs of duct dilation and visible stones, which determines the appropriate imaging sequence and the timing of surgical consultation. Clinical pathways based on pain and cholestasis criteria are used. [41]

In children at risk, a targeted search is carried out for the causes of hemolysis, cystic fibrosis, ileal diseases, and drug factors - this affects the prognosis and recurrence of stone formation after treatment. [42]

Table 3. Minimum diagnostic set

Stage	What to do	For what
Laboratory	Bilirubin, alkaline phosphatase, gamma-glutamyl transferase, amylase, lipase	Evaluation of cholestasis and pancreatitis
1st line visualization	Ultrasound of the abdominal cavity	Detection of stones and signs of cholecystitis
Clarification of ducts	Magnetic resonance cholangiopancreatography	Finding stones in ducts without invasion
Treatment and diagnostic step	Endoscopic retrograde cholangiopancreatography when indicated	Removal of stones from the duct
Etiological search	Hemolysis tests, drug evaluation, and comorbidities	Relapse prevention

Differential diagnosis

Biliary pain is distinguished from functional dyspepsia and gastroduodenitis by its typical duration of more than 30 minutes, its independence from bowel movements, and its association with fatty foods. Ultrasound confirms the presence of stones and thickening of the wall due to inflammation. [43]

Mechanical jaundice is differentiated from hepatitis and hemolysis by the predominance of direct bilirubin and signs of obstruction on imaging. Magnetic resonance cholangiopancreatography helps distinguish stones from congenital duct cysts. [44]

Acute abdomen with right-sided pain requires the exclusion of appendicitis and lower lobe pneumonia, which is achieved through a combination of clinical, laboratory, ultrasound, and radiographic examination. In pancreatitis, lipase and ultrasound findings are used as a guide. [45]

In hemolytics, pain in the right hypochondrium and jaundice may have a multicomponent nature: hemolysis plus obstruction; parallel assessment by a hematologist and early communication with a surgeon are necessary to prevent recurrence. [46]

Table 4. Differential benchmarks

State	Key markers	Visualization	Tactics
Biliary pain	Prolonged pain >30 minutes, cholestasis	Stones on ultrasound	Surgeon's plan based on indications
Hepatitis	Cytolysis predominates	Without obstruction	Etiotropic therapy
Hemolysis	Indirect bilirubin ↑	There may be no stones	Treatment of hemolysis, bladder screening
Choledochal cyst	Cholestasis, infections	Dilation of ducts without stones	Surgical correction

Treatment

Asymptomatic gallstones in children without high-risk factors are often monitored clinically: dietary modification, weight management, and family education about signs of complications are recommended. Exceptions include patients with hemolysis and specific anatomical conditions where the risk of complications is high. [47]

In symptomatic, uncomplicated cases, laparoscopic cholecystectomy is the standard procedure. In children, the procedure has a low complication rate and a short hospital stay, while early mobilization and nutrition are included in accelerated recovery protocols. Preoperative antibiotics are not required unless there are signs of cholecystitis. [48]

For common bile duct stones, a stepwise approach is used: risk stratification, magnetic resonance cholangiopancreatography for intermediate risk, and therapeutic endoscopy for high risk or confirmed stone presence. Some centers perform simultaneous laparoscopic removal of duct stones during cholecystectomy. [49]

Acute calculous pancreatitis requires fluid therapy, pain relief, early enteral nutrition, and treatment of the underlying cause. The timing of cholecystectomy is determined after the inflammation has subsided to prevent recurrence; in cases of duct obstruction, early endoscopic decompression is preferred. [50]

Acute cholangitis is an emergency: in addition to empirical antibiotic therapy, rapid decompression of the bile ducts, most often endoscopic, is key. Delayed stone evacuation increases the risk of sepsis, so routes include expedited access to endoscopy. [51]

Ursodeoxycholic acid dissolution therapy in children has limited efficacy and is indicated selectively for small, uncomplicated cholesterol stones and biliary sludge, especially drug-induced, with mandatory dynamic monitoring. For pigment stones and severe symptoms, the method is ineffective. [52]

Extracorporeal lithotripsy is rarely used and is considered only in select centers and cases, given the availability of minimally invasive surgery and endoscopy. In pediatrics, preference is given to proven and widely available methods with a predictable safety profile. [53]

Children with sickle cell disease and hereditary spherocytosis are often recommended to undergo elective cholecystectomy even with minimal symptoms due to the high risk of complications and recurrence, especially with visualized stones and sludge. The decision is made in consultation with a hematologist and surgeon. [54]

Lifestyle modification is essential for everyone: normalizing body weight, limiting excessively fatty foods, adequate hydration, and physical activity reduce the risk of new stones and improve treatment outcomes. Families are given clear recommendations and signs requiring urgent attention. [55]

Antibiotics are not indicated for uncomplicated cholelithiasis. If signs of acute cholecystitis or cholangitis are present, antibacterial therapy is prescribed according to local protocols prior to decompression and surgery, with subsequent de-escalation. [56]

Table 5. Choice of treatment tactics

Scenario	The basic approach
Asymptomatic stones without high risk	Observation, lifestyle modification
Symptomatic bladder stones	Laparoscopic cholecystectomy
Suspected duct stones	Risk stratification, magnetic resonance cholangiopancreatography, endoscopy as indicated
Acute pancreatitis due to stones	Support, early nutrition, relief of obstruction, elective cholecystectomy
Hemolytic diseases	Low threshold for elective cholecystectomy

Prevention

Primary prevention includes maintaining a normal body weight, a diet that limits excess saturated fats and sugars, adequate physical activity, and hydration. These measures reduce bile lithogenicity and the risk of stone formation. [57]

Rational pharmacotherapy suggests caution when prescribing ceftriaxone for long periods, especially in children with additional risk factors; monitoring is used and alternatives are selected if necessary. [58]

In children with hemolytic anemia, regular ultrasound examinations are recommended for early detection of sludge and stones and planning of treatment before complications develop. Interdisciplinary monitoring reduces the risk of emergency situations. [59]

Following an episode and treatment, it is important to educate the family about the signs of recurrence and complications, as well as support long-term lifestyle modification to prevent new stones.[60]

Forecast

The prognosis for symptomatic cases after laparoscopic cholecystectomy is favorable; most children quickly return to normal activity. Proper timing and routes of the procedure reduce the risk of rehospitalization. [61]

In choledocholithiasis, modern endoscopic and laparoscopic technologies provide a high rate of complete sanitation with a low incidence of serious complications, provided the algorithms are followed. An experienced team is required. [62]

In hemolytic patients, early elective surgery improves quality of life and reduces the incidence of acute pancreatitis and cholangitis; without intervention, the risk of recurrent episodes remains high. [63]

In drug-induced forms, the prognosis is favorable with discontinuation of the causative drug and correction of factors; in some children, sludge and small stones regress, but if they migrate into the ducts, active treatment is required. [64]

FAQ

Does this disease occur in children or only in adolescents?
It can occur at any age, including in infants with hemolysis and parenteral nutrition, but is more often diagnosed in adolescents, especially in those with obesity. [65]

Is it always necessary to remove the gallbladder if stones are found?
No. Asymptomatic gallstones are often observed in children without high-risk factors. Surgery is indicated for pain, complications, and in certain risk groups, such as hemolysis. [66]

Will ursodeoxycholic acid help dissolve stones?
It sometimes helps with small cholesterol stones and sludge, but its effectiveness is limited, and it's of little use for pigment stones; the decision is made by a doctor based on the composition of the stones and symptoms. [67]

What are the dangers of common bile duct stones?
They cause cholestasis, cholangitis, and pancreatitis; the standard treatment is endoscopic stone removal or a combined laparoscopic technique, depending on the center's route. [68]

Why might sludge or stones appear after taking an antibiotic?
Ceftriaxone forms salts with calcium that precipitate in bile; in most children, the changes are reversible after discontinuation, but sometimes the stones migrate and require intervention. [69]