Yellow urticaria in a patient with decompensated alcoholic cirrhosis triggered by intravenous albumin infusion: A case report

Abstract

BACKGROUND

Yellow urticaria (YU) is a rare urticarial subtype in which wheals turn distinctly yellow due to bilirubin depositing in the dermis. It surfaces exclusively in patients with significant hyperbilirubinemia. Worldwide, approximately 30 cases have appeared in the literature since its inaugural description in 1969.

CASE SUMMARY

Here is the first documented case of YU in Lebanon. A 70-year-old male with decompensated alcoholic liver cirrhosis (Child-Pugh Class C, score 11) developed an anaphylactoid reaction to intravenous (IV) human albumin infusion. The reaction produced dyspnea, hypotension (systolic blood pressure less than 90 mmHg) and urticarial plaques. Pre-existing hyperbilirubinemia (total bilirubin 10.5 mg/dL with a predominantly direct fraction of 7.2 mg/dL) rendered the wheals strikingly yellow. Management with IV hydrocortisone, topical emollients and antihistamines achieved complete lesion resolution within 24 hours despite persistent hyperbilirubinemia.

CONCLUSION

YU can arise in the setting of predominantly direct hyperbilirubinemia and can be precipitated by blood product infusions. The swift resolution confirms that the urticarial component follows its own natural timeline independently of the underlying hyperbilirubinemia.

Key Words: Albumin reaction; Anaphylaxis; Bilirubin; Cirrhosis; Hyperbilirubinemia; Yellow urticarial; Case report

Core Tip: Yellow urticaria (YU) is a rare urticarial subtype in which wheals appear yellow due to bilirubin deposition in the dermis during mast-cell degranulation, occurring exclusively in the context of hyperbilirubinemia. We report Lebanon’s first documented case: A 70-year-old male with decompensated alcoholic cirrhosis (Child-Pugh Class C) and predominantly direct hyperbilirubinemia who developed YU following an anaphylactoid reaction to intravenous albumin infusion. Lesions resolved within 24 hours despite persistent hyperbilirubinemia, confirming that urticaria and bilirubin elevation are independent co-existing conditions.

INTRODUCTION

Few dermatological findings stop a clinician in their tracks the way a genuinely yellow hive does. Urticaria itself is common enough: Pruritic wheals erupt suddenly accompanied by erythema and edema and then vanish without scarring within 24 hours[1,2]. Yellow urticaria (YU) is something else entirely. In this rare subtype, circulating bilirubin elevated by an underlying hepatic or biliary condition infiltrates the dermis precisely when mast-cell degranulation drives a surge in local vascular permeability[1,3]. The bilirubin binds avidly to dermal elastin fibers within the nascent wheal and imparts its unmistakable golden hue. Crucially, the yellow color is an epiphenomenon; the urticarial pathophysiology is identical to that of ordinary urticaria.

Since Clarke[4] first characterized the entity in 1969, roughly 30 cases have entered the global literature. Cirrhosis accounts for approximately 61.1% of reported cases followed by liver malignancy (16.7%) and viral hepatitis (5.6%)[5-8]. The most frequent triggers are pharmacological agents (32%) and infectious stimuli (16%) while 28% of cases remain idiopathic[5]. The present report introduces the first documented case of YU in Lebanon, arising in a patient with decompensated alcoholic cirrhosis in the context of an anaphylactoid reaction to intravenous (IV) human albumin infusion.

CASE PRESENTATION

Chief complaints

A 70-year-old male presented following a motor vehicle accident producing polytrauma including head injury and a fractured right hip. During hospitalization he developed an acute systemic reaction consisting of dyspnea, hemodynamic instability and pruritic yellow-colored urticarial plaques over the lower extremities and abdomen, occurring approximately 20-30 minutes after initiation of an IV human albumin infusion.

History of present illness

Intravenous human albumin was administered for hypoalbuminemia and ascites in the context of Child-Pugh Class C cirrhosis, a well-recognized indication for prevention of circulatory dysfunction and management of refractory ascites. This represented the patient’s first documented IV albumin exposure. Approximately 20 minutes to 30 minutes after infusion commencement (25% human albumin solution, 100 mL via peripheral IV catheter at roughly 1 mL/minute) an acute systemic reaction erupted: Dyspnea, hypotension (SBP less than 90 mmHg; mean arterial pressure (MAP) approximately 60 mmHg) and an urticarial skin rash consistent with anaphylactoid reaction. The infusion was immediately discontinued. Continuous hemodynamic monitoring documented a blood pressure nadir of 82/50 mmHg, heart rate 108 bpm, respiratory rate 24/minute and oxygen saturation of 93% on 2 L/minute nasal cannula.

Within hours of the reaction, well-demarcated raised pruritic yellow-colored plaques emerged across the lower extremities and lower abdomen (Figure 1). The characteristic yellow pigmentation was attributed to bilirubin deposition within the urticarial wheals facilitated by the underlying hyperbilirubinemia. Wheals initially clustered over the lower abdomen and bilateral lower extremities before extending to the inguinal and periumbilical regions over the ensuing 2 hours to 3 hours. At peak distribution approximately 10 to 15 discrete wheals were identified ranging from 2 cm to 7 cm in largest diameter. The patient reported severe pruritus rated 8/10 on the Numerical Rating Scale (NRS). No angioedema, mucosal involvement or bronchospasm occurred at any time point.

Figure 1 Yellow, raised, edematous urticarial plaques on the lower abdomen, lower extremities, and inguinal areas. A and B: The characteristic yellow coloration results from bilirubin deposition in the dermis during mast-cell-mediated wheal formation, in the context of significant underlying hyperbilirubinemia.

History of past illness

The patient carried established diagnoses of hypertension and paroxysmal atrial fibrillation. Apixaban 2.5 mg twice daily had been prescribed for stroke prophylaxis, initiated without prior formal hepatic function assessment, a clinical oversight recognized only in retrospect. A documented penicillin allergy was on record. No prior liver disease diagnosis had been formally established before this admission.

Personal and family history

The patient had a longstanding personal history of heavy ethanol consumption of roughly 80 g to 140 g per day (equivalent to approximately half to a full standard bottle of whiskey daily) sustained over 40 years alongside 60 pack-years of tobacco use. No family history of liver disease, hereditary cholestatic disorders, hypersensitivity conditions or autoimmune hepatic disease was elicited. No prior allergic reactions to blood products or colloid solutions had been documented.

Physical examination

On examination the patient was alert and oriented. Admission vital signs were: Blood pressure 95/60 mmHg (MAP 72 mmHg), heart rate 98 bpm, respiratory rate 18/minute, temperature 37.4 °C and oxygen saturation 96% on room air. Bilateral scleral icterus was evident. Generalized cutaneous jaundice spread across the trunk, abdomen and extremities, consistent with markedly elevated total bilirubin (10.5 mg/dL). The patient’s baseline integument was therefore already icteric before any urticarial lesion appeared, a point of direct relevance to the subsequent yellow discoloration of wheals. Abdominal examination revealed distension with shifting dullness consistent with ascites. No asterixis was present on initial assessment.

Laboratory examinations

Key laboratory findings told a compelling story. Total bilirubin stood at 10.5 mg/dL with the direct (conjugated) fraction dominating at 7.2 mg/dL (68.6% of total), pointing toward severe hepatocellular cholestasis rather than hemolytic disease. Hepatic synthetic function was severely compromised: Albumin 2.2 g/dL and international normalised ratio (INR) 1.9. Thrombocytopenia (platelets 98 × 10³/µL) and macrocytosis (mean corpuscular volume 105 fL) reflected portal hypertension-related hypersplenism and alcohol-related bone marrow suppression respectively. Viral hepatitis serologies (hepatitis B surface antigen and anti-hepatitis C virus) were negative. Apixaban was discontinued once decompensated cirrhosis was recognized. Complete laboratory results appear in Table 1.

Table 1 Laboratory results at admission.

Parameter	Value	Reference range	Interpretation
Liver function
Total bilirubin (mg/dL)	10.5	0.2-1.2	↑ markedly elevated
Direct bilirubin (mg/dL)	7.2	0-0.3	↑↑ predominantly direct
Indirect bilirubin (mg/dL)	3.3	0.2-0.9	↑ elevated
ALT (U/L)	68	7-56	↑ mildly elevated
AST (U/L)	95	10-40	↑ elevated
ALP (U/L)	210	44-147	↑ elevated
GGT (U/L)	320	8-61	↑↑ markedly elevated
Albumin (g/dL)	2.2	3.5-5.0	↓ low - hepatic synthetic failure
INR	1.9	0.8-1.1	↑ coagulopathy
PT (seconds)	22	11-13.5	↑ prolonged
Renal function & electrolytes
Creatinine (mg/dL)	1.3	0.7-1.3	Upper normal
BUN (mg/dL)	28	7-20	↑ mildly elevated
Sodium (mEq/L)	132	136-145	↓ hyponatremia
Potassium (mEq/L)	4.1	3.5-5.1	Normal
Complete blood count
Hemoglobin (g/dL)	10.2	13.5-17.5	↓ anemia
Platelets (× 103/µL)	98	150-400	↓ thrombocytopenia
MCV (fL)	105	80-100	↑ macrocytosis
Coagulation & inflammatory markers
aPTT (seconds)	42	25-35	↑ prolonged
Fibrinogen (mg/dL)	180	200-400	↓ low
CRP (mg/L)	48	< 5	↑↑ significantly elevated
Ammonia (µmol/L)	72	9-33	↑ elevated
HBsAg/anti-HCV	Negative	Negative	—

ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; aPTT: Activated partial thromboplastin time; AST: Aspartate aminotransferase; BUN: Blood urea nitrogen; CRP: C-reactive protein; GGT: Gamma-glutamyl transferase; INR: International normalised ratio; MCV: Mean corpuscular volume; HBsAg: Hepatitis B surface antigen; HCV: Hepatitis C virus; PT: Prothrombin time.

Imaging examinations

Abdominopelvic computed tomography confirmed an irregular hepatic contour, splenomegaly, portal hypertension and moderate ascites, consistent with established cirrhosis. The Child-Pugh score reached 11 (Class C) indicating severe hepatic impairment. Esophagogastroduodenoscopy could not be performed acutely due to hemodynamic instability so the status of esophageal varices was not formally assessed at admission, a clinical limitation acknowledged herein. Subsequent abdominal ultrasound performed during follow-up confirmed intrahepatic cholestasis with no biliary duct dilation, consistent with hepatocellular rather than obstructive cholestasis.

MULTIDISCIPLINARY EXPERT CONSULTATION

The patient was managed jointly by the intensive care unit team and the hepatology service. The intensive care unit (ICU) team directed hemodynamic resuscitation and pharmacological management of the anaphylactoid reaction. The hepatology service supervised management of decompensated cirrhosis including diuretic therapy for ascites, nutritional support, alcohol cessation counselling and monitoring for hepatic encephalopathy. Liver biopsy was deferred given the patient’s coagulopathy and clinical complexity. The diagnosis of YU was established on clinical grounds by the treating team without formal dermatology consultation.

FINAL DIAGNOSIS

YU triggered by an anaphylactoid reaction to IV human albumin infusion, occurring in the setting of decompensated alcoholic liver cirrhosis (Child-Pugh Class C, score 11) with predominantly direct (conjugated) hyperbilirubinemia (total bilirubin 10.5 mg/dL; direct fraction 7.2 mg/dL). The yellow discoloration of urticarial wheals was attributed to bilirubin deposition within the dermis during mast-cell-mediated increased vascular permeability against a background of significant pre-existing hyperbilirubinemia.

TREATMENT

The albumin infusion was immediately discontinued upon onset of the anaphylactoid reaction. Transient vasopressor support was initiated given the hemodynamic compromise. The ICU team administered IV hydrocortisone 250 mg as a single dose given the urgency of the hemodynamic situation followed subsequently by IV chlorpheniramine maleate 10 mg. Symptomatic skin care was provided with a topical emollient/hydrating cream. Intravenous albumin was permanently withheld for the remainder of the hospitalization and alternative management for hypoalbuminemia and ascites was employed. Concurrent management of decompensated cirrhosis included diuresis for ascites, nutritional supplementation and alcohol cessation counselling.

OUTCOME AND FOLLOW-UP

Urticarial lesions began subsiding approximately 4 hours to 6 hours after infusion cessation and pharmacological treatment and resolved completely by 24 hours. Pruritus correspondingly diminished from NRS 8/10 at peak to NRS 2/10 at 8 hours and 0/10 at 24 hours. All urticarial wheals resolved completely within 24 hours despite persistence of significant hyperbilirubinemia (total bilirubin remained above 8 mg/dL at 24-hour follow-up). At 48-hour follow-up no lesion recurrence was noted and hemodynamic parameters had returned to the patient’s admission baseline. Surveillance for hypersensitivity recurrence continued over subsequent hospital days without incident.

DISCUSSION

YU has a way of making itself unmistakably known. It announces significant hepatic or biliary disease through the skin and demands the clinician's attention. Its pathophysiology pivots on the simultaneous presence of two independent processes: Conventional urticaria arising from any trigger alongside significant hyperbilirubinemia. Mast-cell degranulation releases histamine and vasoactive mediators producing vasodilation and augmented capillary permeability in the superficial dermis. Plasma, along with the bilirubin it transports, extravasates into the interstitium where bilirubin binds tenaciously to elastin fibers within the wheal and produces the distinctive golden discoloration[1,3]. Worth emphasizing plainly: Elevated bilirubin does not cause urticaria. Rather, conventional urticaria occurring against a backdrop of hyperbilirubinemia produces yellow wheals.

This case contributes several noteworthy observations to the existing literature (summarized in Table 2). First, it constitutes Lebanon's inaugural documented case and, to our knowledge, the first case specifically triggered by an IV human albumin infusion. A conceptually analogous precedent does exist: Hardy et al[9] described YU following fresh frozen plasma transfusion in a patient with end-stage liver disease. Albumin-induced anaphylactoid urticaria in this context has not been previously reported. The implication is clear: Any urticarial trigger including blood products administered for legitimate therapeutic indications can precipitate YU in a hyperbilirubinemic patient.

Table 2 Summary of previously published cases of yellow urticaria.

Ref.	Year	Age/sex	Underlying condition	Peak bilirubin (mg/dL)	Urticaria trigger	Treatment
Clarke[4]	1969	Adult/male	Hepatic cirrhosis	Elevated (NR)	Idiopathic	Antihistamines
Nava Cruz et al[2]	2017	57 years/female	Biliary pancreatitis	8.4	Idiopathic	Antihistamines
Combalia et al[1]	2017	63 years/male	Cirrhosis	9.3	Drug	Antihistamines
Combalia et al[1]	2017	38 years/female	AIH/PBC overlap	7.8	Idiopathic	Antihistamines
Çakıcı et al[3]	2021	Adult/NR	Viral hepatitis B	5.9	Idiopathic	Antihistamines
Mendes et al[10]	2018	Adult/NR	ARV-induced liver injury	4.5	Drug (ARV)	Cessation + antihistamines
Hardy et al[9]	2022	67 years/male	End-stage liver disease	12.1	FFP transfusion	Antihistamines
Kalsi et al[6]	2024	Adult/NR	Acalabrutinib hepatotoxicity	6.8	Drug	Cessation + steroids
Toujani et al[8]	2023	33 years/female	AIH + PBC overlap	6.2	Idiopathic	Antihistamines
Gao et al[7]	2025	Adult/NR	Uncommon aetiology (NR)	NR	Idiopathic	Antihistamines
Present case	2025	70 years/male	Decompensated alcoholic cirrhosis (CPC 11)	10.5 (direct 7.2)	IV albumin (anaphylactoid)	IV hydrocortisone + chlorpheniramine + emollients

AIH: Autoimmune hepatitis; ARV: Antiretroviral; CPC: Child-Pugh Class; FFP: Fresh frozen plasma; NR: Not reported; PBC: Primary biliary cholangitis; IV: Intravenous.

Second, the predominantly direct (conjugated) hyperbilirubinemia in this case (68.6% of total) reflects severe hepatocellular cholestasis rather than hemolytic disease. Published cases do not consistently report bilirubin fractionation and that gap matters clinically. Both direct and indirect bilirubin circulate in plasma and can deposit in the skin; jaundice manifests regardless of which fraction predominates provided total bilirubin exceeds approximately 2 mg/dL to 3 mg/dL. YU has been documented in biliary pancreatitis, a condition producing cholestatic (direct) hyperbilirubinemia via extrahepatic bile duct obstruction without hepatocellular dysfunction[2]. This supports a key principle: It is the circulating bilirubin level rather than its fraction or mechanism that governs whether yellow discoloration of wheals occurs. In theory, states of severe indirect hyperbilirubinemia such as significant hemolysis could also yield YU if levels climb sufficiently high though no such case has yet appeared in print.

Third, the complete wheal resolution within 24 hours despite persistent hyperbilirubinemia is mechanistically illuminating. Urticarial wheals characteristically resolve within 24 hours because mast-cell mediator release is a self-limited process. The trigger here was a discrete anaphylactoid event; once the albumin infusion was halted and the immunological stimulus removed, the urticarial component abated along its expected natural timeline. Persistent hyperbilirubinemia is irrelevant to wheal duration because without a recurring urticarial trigger no new wheals form. This is distinct from residual yellow skin pigmentation reported in some cases, which can persist for a median of 4 days (range 2 days to 10 days) after wheal resolution due to ongoing bilirubin-elastin binding[5]. In the present case, residual pigmentation also cleared rapidly, possibly reflecting the anti-inflammatory efficacy of systemic corticosteroids.

Regarding pharmacological management: Second-generation H1 antihistamines are the recognized first-line therapy for urticaria and they remain the pharmacological cornerstone of YU treatment[5,10]. In anaphylaxis or severe systemic reactions, intramuscular epinephrine is the acute intervention of choice followed by IV corticosteroids and antihistamines. Here, IV hydrocortisone was administered first given the hemodynamic urgency and antihistamines followed, a clinically appropriate sequencing in a critically ill patient with concurrent anaphylaxis and urticaria. Long-term management requires addressing the underlying cause of hyperbilirubinemia though this does not directly influence the acute urticarial episode.

Hall’s stain (Hall’s bile salt stain) is the histochemical reference technique for confirming bilirubin deposition in the dermis, demonstrating characteristic olive-green bilirubin crystals in tissue biopsy specimens[1]. No biopsy was undertaken here given the clinical transparency of the presentation and the patient’s severe coagulopathy (INR 1.9, prothrombin time 22 seconds, activated partial thromboplastin time 42 seconds, fibrinogen 180 mg/dL, platelets 98 × 10³/µL), which posed unacceptable procedural hemorrhagic risk in an already critically ill patient. The absence of histological confirmation via Hall staining is a genuine methodological limitation that reduces the diagnostic grade of this case and must be stated plainly. Diagnosis rested on four clinical pillars: (1) Characteristic yellow-pigmented wheals superimposed on pre-existing jaundice; (2) A strict temporal relationship between albumin infusion and wheal onset; (3) Complete resolution within 24 hours following drug withdrawal and antihistamine therapy; and (4) The absence of any alternative dermatological explanation. Future cases in less coagulopathic patients should incorporate histological confirmation wherever feasible.

An important mechanistic question lingers: Was the hypersensitivity reaction directed against human albumin protein itself or against excipients in the commercial formulation? Standard 25% human albumin solutions contain stabilizing additives including sodium octanoate (caprylate; 0.08 mmol/mL) and sodium N-acetyltryptophanate (0.08 mmol/mL) and both have been implicated as independent allergens in documented hypersensitivity reactions. Without component-specific skin prick testing or intradermal testing to isolated albumin protein and individual excipients, the causal attribution remains unresolved. The distinction carries genuine clinical relevance: Patients sensitized specifically to caprylate or acetyltryptophanate excipients might potentially tolerate albumin formulations using alternative stabilizers whereas those sensitized to the albumin protein itself would require avoidance of all albumin products. This is acknowledged as a formal limitation of the causal chain.

Formal allergen verification via skin prick testing, intradermal testing or basophil activation testing was not performed during the acute admission given the patient’s critical hemodynamic status and active coagulopathy. Outpatient allergen testing following clinical stabilization would have provided stronger mechanistic evidence. Nevertheless the strict temporal correlation between infusion initiation and reaction onset (20 minutes to 30 minutes) combined with durable resolution upon infusion discontinuation constitutes strong circumstantial evidence for direct causality. The absence of prior albumin exposure makes a Type I immunoglobulin E (IgE)-mediated sensitization-dependent mechanism less probable as the primary pathway and points instead toward non-IgE-mediated mechanisms such as direct pharmacological mast-cell degranulation, complement activation (C3a/C5a) or excipient-mediated effects. Future clinical encounters with albumin hypersensitivity should include allergen verification where feasible to strengthen the evidentiary chain and guide safe management.

Finally, this case stands apart from most previously published cases (Table 2) in several respects: The severity of hepatic decompensation (Child-Pugh Class C, score 11), the polytrauma context, the complex anticoagulation scenario in undiagnosed cirrhosis and the ICU setting in which the diagnosis was established. Collectively these factors underscore that YU can surface in the most critically ill of patients and intensivists must maintain a high index of suspicion when encountering jaundiced skin lesions in the context of liver disease.

CONCLUSION

YU is rare but visually arresting. It represents the co-occurrence of conventional urticaria and significant hyperbilirubinemia. Bilirubin does not cause the urticaria; rather, it infiltrates the wheal during mast-cell degranulation and paints it gold. This case, Lebanon’s first documented instance, was triggered by an anaphylactoid reaction to IV albumin infusion in a patient with Child-Pugh Class C decompensated alcoholic cirrhosis and predominantly direct hyperbilirubinemia. Lesions resolved within 24 hours following allergen removal consistent with the natural history of an acute urticarial episode and entirely independent of the persistent hyperbilirubinemia. This case broadens the recognized spectrum of YU triggers to include IV albumin and reinforces that the condition can arise in any form of significant hyperbilirubinemia. Its recognition in critically ill patients demands a high index of clinical suspicion and should prompt systematic investigation of underlying hepatic or biliary pathology.