What can cause abdominal tenderness in the right iliac fossa and hypogastric region, with pancytopenia, and what negative symptoms should be asked about?

Differential Diagnosis of Right Iliac Fossa and Hypogastric Tenderness with Pancytopenia

In a 42-year-old woman with pancytopenia and localized right iliac fossa/hypogastric tenderness on palpation, the most critical considerations are typhlitis (neutropenic enterocolitis), appendicitis, and infectious causes including hepatosplenic candidiasis or visceral leishmaniasis (kala-azar), with the pancytopenia itself suggesting an underlying hematologic disorder or infection that requires urgent evaluation.

Primary Differential Diagnoses

Infectious Causes Related to Pancytopenia

• Visceral leishmaniasis (kala-azar) is a documented cause of pancytopenia (9% of cases in one series) and can present with abdominal pain and hepatosplenomegaly 1
• Enteric fever causes pancytopenia in approximately 30% of pediatric cases and can present with right-sided abdominal pain 2
• Invasive fungal disease, particularly hepatosplenic candidiasis, typically develops after neutrophil recovery in patients with prolonged pancytopenia and presents with persistent fever, hepatosplenomegaly, and increased alkaline phosphatase 3
• Falciparum malaria is a treatable and reversible cause of pancytopenia that may present with abdominal symptoms 1

Appendicitis

• Acute appendicitis remains a critical consideration despite pancytopenia, as the classic presentation (periumbilical pain migrating to RLQ, fever, leukocytosis) occurs in only 50% of patients 3
• In patients with pancytopenia, the typical leukocytosis may be absent, making diagnosis more challenging 3
• CT abdomen/pelvis with IV contrast (without enteral contrast) has sensitivity 90-100% and specificity 94.8-100% for appendicitis diagnosis 3

Typhlitis (Neutropenic Enterocolitis)

• Right-sided abdominal pain in the setting of pancytopenia and neutropenia should raise immediate concern for typhlitis, a life-threatening condition affecting the cecum and right colon 3
• This condition occurs in critically ill patients with profound neutropenia and carries high mortality if not recognized early 3

Hematologic Causes

• Aplastic anemia is the most common cause of pancytopenia (20.72% of cases) and may present with hypocellular marrow 1
• Systemic lupus erythematosus (SLE) causes pancytopenia and can present with serositis including peritonitis 1
• Hypersplenism from chronic liver disease (11.71% of pancytopenia cases) can cause splenomegaly with referred pain to the right lower quadrant 1

Critical Negative Symptoms to Assess

Infection-Related Symptoms

• Fever pattern: Persistent fever despite broad-spectrum antibiotics suggests invasive fungal disease; recurring febrile episodes after initial defervescence are concerning for fungal infection 3
• Night sweats and weight loss: Suggest chronic infection (kala-azar, tuberculosis) or malignancy 1
• Rigors and high-grade fever: More typical of bacterial infections including enteric fever 2

Gastrointestinal Symptoms

• Nausea and vomiting: Present in 38-48% of elderly patients with appendicitis but absence does not exclude diagnosis 3
• Diarrhea: Particularly bloody diarrhea suggests typhlitis or infectious colitis; diarrhea with bacteremia after cardiopulmonary resuscitation suggests non-occlusive mesenteric ischemia 3
• Dysphagia or retrosternal burning: May indicate fungal esophagitis in immunocompromised patients with pancytopenia 3

Bleeding and Thrombocytopenic Symptoms

• Mucosal bleeding, petechiae, or purpura: Severe thrombocytopenia (platelets ≤20 × 10⁹/L) occurs in 25.2% of megaloblastic anemia patients and 45.1% have skin/mucosal bleeding 2
• Gastrointestinal bleeding: Passage of maroon or bright red blood suggests mesenteric ischemia, particularly in critically ill patients 3

Peritoneal Signs

• Absence of peritonitis signs: Only 5.3-14.5% of elderly patients with appendicitis show peritonitis, so absence does not exclude acute pathology 3
• Rebound tenderness and guarding: Present in 64.7% of patients over 65 with appendicitis 3
• Murphy's sign: Has sensitivity of only 48% in elderly patients, so negative sign does not exclude cholecystitis 3

Systemic and Constitutional Symptoms

• Prolonged fever without localizing signs: Suggests aplastic anemia, leukemia, or systemic infection 1
• Oral lesions or mucositis: Oral candidiasis may be difficult to distinguish from chemotherapy-induced mucositis 3
• Visual changes: Cotton wool spots suggest fungal endophthalmitis, which develops after neutrophil recovery in systemic candidiasis 3
• Headache or altered mental status: Cryptococcal meningoencephalitis can occur in hematologic malignancy patients 3

Medication and Exposure History

• Recent antibiotic use: Antibiotic-refractory fever in prolonged granulocytopenia suggests fungal infection 3
• Vasopressor use: Norepinephrine, epinephrine, vasopressin, and digoxin can worsen mesenteric ischemia in critically ill patients 3
• Drug-induced pancytopenia: Certain antibiotics and anti-HCV drugs can cause iatrogenic pancytopenia 4

Diagnostic Approach

Immediate Laboratory Evaluation

• Complete blood count with differential: Confirm pancytopenia severity and assess for leukemia or myelodysplastic syndrome 5
• C-reactive protein: Elevated in 94% of appendicitis cases and more sensitive than white blood cell count (P < 0.05) 6
• Metabolic panel: Assess for hyperkalemia and severe metabolic acidosis suggesting bowel infarction 3
• Liver function tests: Elevated alkaline phosphatase suggests hepatosplenic candidiasis 3

Imaging

• CT abdomen/pelvis with IV contrast is the most useful diagnostic modality with sensitivity 85.7-100% and specificity 94.8-100% for acute abdominal pathology 3
• CT can identify appendicitis, typhlitis, bowel ischemia, hepatosplenic lesions, and free fluid 3
• Ultrasound has limited sensitivity (51.8%) and specificity (81.4%) for appendicitis, particularly when the appendix is not visualized (45% of cases) 3

Specialized Testing Based on Clinical Suspicion

• Blood cultures: Essential before initiating antifungal therapy in suspected invasive fungal disease 3
• Bone marrow examination: Required to establish etiology of pancytopenia and exclude leukemia or aplastic anemia 5
• Serology for kala-azar: If endemic exposure and hepatosplenomegaly present 1

Clinical Pitfalls to Avoid

• Do not dismiss appendicitis based on absence of leukocytosis in a pancytopenic patient; CRP elevation may be the only laboratory abnormality 6
• Do not delay imaging for oral contrast administration; CT with IV contrast alone has equivalent diagnostic accuracy (sensitivity 90-100%, specificity 94.8-100%) without treatment delay 3
• Do not attribute all symptoms to pancytopenia; treatable causes like megaloblastic anemia, infections, and SLE are reversible and early diagnosis is life-saving 1
• Recognize that clinical signs may be attenuated in immunocompromised patients; unexplained abdominal distension may be the only sign of intestinal ischemia in 25% of ICU patients 3
• Obtain tissue diagnosis before initiating antifungal therapy when possible, as histological and cultural evidence provides the highest level of diagnostic certainty 3