What are the differential diagnoses and initial investigation plan for a 50‑year‑old adult presenting with multiple eruptive dermatofibromas, weight loss, night sweats, left lower quadrant abdominal pain, and constipation?

Differential Diagnoses and Investigation Plan

Primary Differential Diagnoses

The constellation of multiple eruptive dermatofibromas with constitutional symptoms (weight loss, night sweats) and gastrointestinal manifestations in a 50-year-old strongly suggests an underlying systemic autoimmune or lymphoproliferative disorder, with systemic lupus erythematosus, inflammatory bowel disease, and lymphoma being the most critical diagnoses to exclude.

Most Likely Diagnoses to Investigate

• Systemic Lupus Erythematosus (SLE): Multiple dermatofibromas are strongly associated with SLE, with more than half of reported cases of multiple dermatofibromas occurring in patients with this condition 1, 2. The combination of constitutional symptoms (weight loss, night sweats) with dermatologic findings makes this a priority diagnosis 3.

• Inflammatory Bowel Disease (Crohn's Disease): The left lower quadrant pain and constipation, combined with constitutional symptoms (weight loss, night sweats), are classic presentations of IBD 4, 5. Night sweats specifically are documented as a symptom of IBD complications 4.

• Intestinal Lymphoma: The combination of multiple dermatofibromas (suggesting immune dysregulation), constitutional B symptoms (weight loss, night sweats), and gastrointestinal symptoms raises concern for lymphoproliferative disorders 4. Intestinal lymphoma presents with diarrhea, abdominal pain, fever, weight loss, and signs of obstruction 4.

• HIV Infection: Approximately one-third of multiple dermatofibroma cases are associated with HIV infection 1, 2. The immunosuppressed state and constitutional symptoms warrant screening 6.

• Hematologic Malignancy: Multiple eruptive dermatofibromas are associated with hematologic malignancies in 9.4% of cases, and these conditions present with night sweats and weight loss 1.

Investigation Plan

Immediate Laboratory Workup

Initial blood work must include complete blood count with differential, comprehensive metabolic panel, liver function tests, erythrocyte sedimentation rate, and C-reactive protein to assess for anemia, inflammatory markers, and organ dysfunction 5, 7.

• Complete blood count: Assess for anemia (common in IBD and malignancy), leukopenia (SLE), or lymphocytosis (lymphoma) 5.
• Inflammatory markers: CRP is more sensitive than ESR for detecting active inflammation in IBD 5. Elevated inflammatory markers suggest chronic inflammatory disease 7.
• Comprehensive metabolic panel and liver function tests: Essential for baseline assessment and to evaluate for hepatic involvement 5.

Autoimmune Screening

• Antinuclear antibody (ANA) panel: Screen for SLE with reflex to anti-dsDNA, anti-Smith, anti-Ro/SSA, and anti-La/SSB antibodies 3.
• Complement levels (C3, C4): Low levels suggest active SLE 3.
• Anti-Saccharomyces cerevisiae antibodies (ASCA): Positive in Crohn's disease 4.

Infectious Disease Screening

• HIV antibody test with confirmatory testing: Essential given the strong association between HIV and multiple dermatofibromas 1, 2.
• Tuberculosis screening: Interferon-gamma release assay (QuantiFERON-Gold) to exclude tuberculosis, which presents with night sweats, weight loss, and abdominal pain 4.
• Stool studies: Bacterial culture, Clostridium difficile toxin assay, and ova/parasites to exclude infectious colitis 4, 8, 5.

Gastrointestinal-Specific Testing

Fecal calprotectin is essential, with values >250 μg/g triggering urgent gastroenterology referral and ileocolonoscopy 5, 7.

• Fecal calprotectin: Values <100 μg/g suggest lower relapse probability, 100-200 μg/g warrant repeat testing, and >250 μg/g require endoscopic evaluation 5.
• Celiac serology: Tissue transglutaminase IgA with total IgA to exclude celiac disease as a cause of weight loss and gastrointestinal symptoms 7.

Imaging Studies

CT abdomen/pelvis with IV contrast is the gold standard for evaluating complications, achieving 95% sensitivity/specificity for identifying abscesses, strictures, fistulae, or masses 5.

• CT abdomen/pelvis with IV contrast: Evaluate for lymphadenopathy (lymphoma, tuberculosis), bowel wall thickening (IBD, lymphoma), abscesses, or masses 5.
• Chest X-ray: Screen for pulmonary tuberculosis or lymphoma given night sweats and constitutional symptoms 4.

Endoscopic Evaluation

Colonoscopy with terminal ileal intubation and multiple segmental biopsies is the reference standard for IBD diagnosis and can identify lymphoma or other mucosal pathology 5, 7.

• Ileocolonoscopy with biopsies: Obtain multiple biopsies from different colonic segments and terminal ileum, stored in separate containers to map inflammation distribution 5. Diagnostic accuracy increases from 66% to 92% with segmental biopsies versus random sampling 5.
• Biopsy even normal-appearing mucosa: Microscopic colitis can present with normal endoscopic appearance but significant histologic inflammation 8, 7.
• Look for specific features: Granulomas (Crohn's disease, tuberculosis), monoclonal T-cell populations (lymphoma), or crypt architecture distortion (IBD) 4, 5.

Dermatologic Evaluation

• Skin biopsy of dermatofibromas: Confirm diagnosis and exclude other fibrohistiocytic lesions 1.
• Dermatology consultation: Multiple eruptive dermatofibromas warrant workup for underlying immune dysregulation 6.

Critical Pitfalls to Avoid

• Do not rely on CRP alone: Approximately 15-20% of patients with active IBD have normal CRP levels 7.
• Do not defer colonoscopy based on intermediate calprotectin values: If clinical suspicion is high based on symptoms (weight loss, night sweats, abdominal pain), proceed with endoscopy regardless 7.
• Do not perform colonoscopy in severe colitis without experienced endoscopist: Higher perforation risk requires specialist involvement 7.
• Do not dismiss multiple dermatofibromas as benign: This finding represents immune dysregulation and mandates systemic workup 6, 2.

Algorithmic Approach

1. Immediate laboratory workup: CBC, CMP, LFTs, ESR, CRP, HIV, ANA panel, fecal calprotectin 5, 7.
2. If fecal calprotectin >250 μg/g OR constitutional symptoms present: Urgent CT abdomen/pelvis and gastroenterology referral 5, 7.
3. If inflammatory markers elevated OR imaging shows bowel pathology: Proceed to ileocolonoscopy with multiple biopsies 5, 7.
4. If ANA positive: Complete lupus workup with complement levels and specific antibodies 3.
5. If HIV positive OR tuberculosis screening positive: Infectious disease consultation for directed therapy 4, 1.
6. If lymphadenopathy or masses on imaging: Hematology consultation and consider PET scan for lymphoma staging 4.