A CASE REPORT ON WUNDERLICH SYNDROME IN A 32-YEAR-OLD MALE: DIAGNOSTIC AND CLINICAL CHALLENGES

Acute abdominal discomfort can be quite challenging to diagnose accurately especially when pressed with time and when the most common causes do not fit the clinical picture. At all times, a clinician should be able to determine conditions that herald an urgent intervention and those that do not. Severity of pain does not necessarily translate to the severity of underlying condition. There are times when the most agonizing acute abdomen do not demand an operative management. However, there are also instances when even the mildest of abdominal pain will compel immediate action and invasive intervention as seen in life-threatening conditions such as the case of spontaneous renal hemorrhage or Wunderlich Syndrome.

Wunderlich syndrome is a severe and rare condition manifested by an acute onset of spontaneous renal hemorrhage into the pararenal, perirenal or subcapsular spaces in the absence of inciting trauma. According to a study by Parmar, et al., classic symptom complex of flank mass, flank pain and hypovolemic shock makes up for the Lenk triad seen in less than a quarter of patients. More than two thirds of the patients manifest with flank pain as the primary symptom. Given acute flank pain as the universal presenting symptom, the most appropriate to be performed in the emergency department would be an abdominal CT scan. The underlying etiology varies with most cases attributed to renal neoplasms (60-65%), a plethora of renal vascular diseases (20- 30%) and renal infections, cystic disease, coagulation disorders among many others. From a study by Cubillos et. al., Wunderlich syndrome has been described more than a century ago with only 165 cases reported worldwide from 1985 to 1999, reduced further to 102 cases between 2000 and 2016, and eventually to 41 cases between 2016 and 2022, reflecting its rarity. 4 In the Philippines, only one (1) has been documented yet.

Although infrequently reported, it is important for clinicians to have a high index of suspicion for spontaneous renal hemorrhage as this presents with insignificant symptomatology but should be managed critically. Once established, conservative measures must be done to stabilize the patient. Identification of cause should be sought further to decide whether to pursue surgical intervention. At times, renal arterial embolization can be an option if urgent nephrectomy is not required. In this study, a case of Wunderlich syndrome in a young adult presenting with sudden right flank pain, who developed anemia is described. After immediate conservative management, clinicians successfully prevented hemodynamic instability resulting to favorable outcome. This report highlights the prompt diagnosis, optimal management and further elaborate the disease entity.

Case

A 32-year-old hypertensive male presented at the emergency department with a complaint of sudden onset of right flank pain without previous trauma or anticoagulant use. The pain was constant and severe with associated vomiting of previously ingested food and anorexia. The patient denied history of fever, gross hematuria and symptoms of urinary tract infection. On admission, patient was afebrile, displaying moist mucous membranes with a blood pressure of 140/100 mmHg, heart rate of 90 bpm and oxygen saturation of 98% at room air with respiratory rate of 22 breaths per minute. Abdomen was soft but with noted tenderness on the right periumbilical to right lower quadrant area, positive right kidney punch sign and no palpable mass. As patient is a known hypertensive, he is maintained on amlodipine 5mg once a day. He has no past surgical history, no known bleeding disorder and no prior use of anticoagulant therapy or any other medication.

At the emergency room, blood tests showed leukocytosis with neutrophilic predominance (hemoglobin of 16.6 g/dL WBC 13.4k cells/uL, neutrophil 85%) on complete blood count, creatinine was normal at 1.1mg/dL and lipase was negative. Urinalysis showed proteinuria (2+), trace glucosuria and large hematuria with corresponding RBC of 184.86 cells/HPF. At this time, the main considerations were nephrolithiasis and acute appendicitis. Ultrasound was initially requested however, due to unavailability at the time of presentation, CT scan of the whole abdomen was taken instead. Abdominal CT scan with contrast was done revealing (1) significant right perirenal hematoma formation encapsulating the right kidney, approximately measuring 8.4 x 4.8 x 13.6 cm, 53 HU, with active bleeding from a branch of the inferior polar artery of the right kidney; and (2) Small amount of hematoma (extension) at the right subhepatic region and along the right paracolic gutter (figure 1). With the diagnosis of Wunderlich Syndrome (spontaneous renal hemorrhage), the patient was then immediately treated with aggressive volume resuscitation with crystalloids, a broad-spectrum IV antibiotic with Ceftriaxone 1g every 24 hours and pain medications for symptomatic relief. Blood typing was done in preparation for possible blood transfusion. Bleeding parameters were also taken (APTT, prothrombin time, clotting time and bleeding time) which came out normal. On the next day, blood pressure range had declined from 140/100 to 120/80 mmHg-100/70mmHg. Serial CBC showed a normocytic normochromic anemia with a significant drop in hemoglobin from 16.6 g/dL to 9.3 g/dL. Transfusion of two (2) units packed RBC was done which raised the hemoglobin to 11.4 g/dL.

Since there was no clear renal mass or cystic disease on imaging and no hemodynamic instability, surgical management was excluded. Vascular specialist and interventional radiologist were called in where patient underwent right renal angiogram showing hypodense area at the right inferior pole of the right kidney suggesting an area of hematoma formation with no extravasation to suggest active bleeding at the time of the procedure or pseudoaneurysm (figure . Catheterization and embolization were subsequently done with post embolization angiogram showing occlusion of the branches of the right inferior polar artery.

After the procedure, the patient was transferred to cardiac care unit where patient’s systolic blood pressure remained stable at 120-130mmHg. His hemoglobin level was steady at 12.3g/dL with normal renal function (creatinine 1.1mg/dL with an eGFR of 91mL/min/1.73m2) and complete resolution of microscopic hematuria.

Patient was subsequently transferred to the ward. However, he developed high grade fever while on Ceftriaxone. CBC, urinalysis and chest x-rays were repeated and were normal. Perirenal abscess formation was considered at this time and Ceftriaxone was shifted to Meropenem pending blood culture results. Despite escalating the antibiotics, the patient was persistently febrile and was then referred to a urologist for evaluation who agreed with the consideration of perirenal abscess and possible nephrectomy was contemplated. On hospital day 6, repeat CT scan of the whole abdomen with contrast was ordered but due to financial limitations, the patient opted to go home and continue with oral antibiotic Cefixime to complete 2 weeks.

One week after discharge, CBC was done showing no further decline of hemoglobin and a follow up abdominal ultrasound showed right perinephric hematoma measuring 11.3 cm x 9.5 cm x 4.1 cm with an estimated volume of 231.51 mL with complete resolution of the pateint’s fever. During the second follow up (one month after discharge), repeat ultrasound revealed a significant decrease in size of the previously noted right perirenal hematoma at this time measuring 6.2 x 2.9 x 6.6cm with an estimated volume of 64 mL. Overall, the patient had improved well-being.

Discussion

Wunderlich Syndrome (WS) is a rare but potentially fatal condition. This condition is more common in men and appears at an average age of 46 years, with most cases occurring between ages 30 and 60 years old. It usually occurs as an acute entity, but it presents less often in a more subtle but progressive manner. Given the rarity of WS and its life-threatening nature, it is important for a physician to recognize this entity since it is usually confused with other diseases, such as renal stones.

The most common manifestation of WS is flank or abdominal pain seen in 67% of patients, followed by hematuria, either microscopic or gross (40%), a flank mass, and hypovolemic shock (27%), which may all occur in concert or in isolation. The characteristic Lenk triad of flank mass, a flank pain, and hypovolemic shock is appreciated in only an estimated 20% of patients with WS. Proposed theories for developing WS include increased renal vein pressure, changes in intralesional tumor pressure due to blocked vasculature, necrosis and the damage of inherent tumor vasculature. 

Most cases of WS have neoplastic and vascular causes. Angiomyolipomas and renal cell carcinomas (RCCs) are the most common benign and malignant neoplasms seen to have increased probability to cause WS. These are followed by pseudoaneurysms and rupture of renal artery aneurysms, vascular malformations, and vasculitis syndromes, including polyarteritis nodosa, as the second most common etiology. Acquired and hereditary renal cystic diseases, pregnancy, kidney failure, and iatrogenic causes (e.g. systemic anticoagulation) predispose patients to WS. Renal infections, calculus disease, and coagulation disorders are rare causes of WS. 

The diagnosis can be complex, as it can mimic some acute abdominal pathologies. Ultrasound is highly sensitive and valuable for its rapid identification, but its findings must be confirmed with a CT scan. Ultrasound is often useful as a follow-up examination to assess the evolution of the hematoma as it may not allow identification of the cause in most patients with WS. On the other hand, contrast-enhanced CT scan provides additional information beyond that found with ultrasound techniques. It allows dynamic assessment of blood flow in perfused tissues. In addition, MRI may be performed to detect causes of WS in patients with whom the initial or follow-up CT scan did not yield source of bleeding. If the CT scan and MRI are unclear regarding etiology, angiogram is the next recommended approach. Catheter angiography helps to detect the source of bleeding and to identify the vascular causes of WS. Super-selective renovascular catheterization and embolization have increasingly been used as the first-line treatment for prompt control of life-threatening WS and avoidance of radical surgery. If radiological investigations fail to identify the cause, surgical exploration and biopsy is recommended.

There are several management recommendations, which depend on the presence of active bleeding and the patient’s general hemodynamic status. In cases of hemodynamic instability, an urgent radical nephrectomy or hemostasis by interventional radiology should be performed. When active extravasation is detected on imaging, angiography and embolization are the preferred approach, with partial or radical nephrectomy reserved for neoplastic causes or refractory bleeding. However, if hemodynamically stable as described in the case, recent studies suggest an initial trial of conservative therapy with hydration, pain management, blood product replacement, and volume resuscitation with intravenous fluids; if there is concern for an infectious etiology, appropriate antibiotic therapy should be started which had also been given to the patient above. Selective arterial embolization is another method to control active bleeding, and many authors recommend it as the definitive therapy. Serial CT scans should be performed to monitor bleeding afterwards. Nevertheless, nephrectomy is still the first-line approach.

Among the plethora of causes responsible for left flank pain, Wunderlich Syndrome, although rare, needs due consideration while ruling out the common differentials. In most patients, the etiology cannot be detected using imaging technique alone. The timing and choice of diagnostic imaging is important, as it helps guide treatment by identifying the cause of the disease. However, if the patient is in shock or has life-threatening symptoms, imaging may be delayed until the patient's condition has stabilized. Conservative management with follow-up imaging is a good approach to avoid unnecessary surgery. By delving into this rare occurence and its characteristics and clinical outcomes, the goal is to shed insights on the complexities and subtleties of a dreaded complication, a relatively benign condition that can rise.