The Unusual Suspect - Herpes Zoster as the Culprit for Severe Abdominal Pain. A Case Report

Abstract

Reactivation of herpes zoster leading to disseminated and visceral organ involvement is an uncommon phenomenon and almost always associated with immunocompromised patients. Visceral herpes zoster is a challenging diagnosis to make as patients typically present with severe abdominal pain which precedes the typical rash of herpes zoster. We describe the case of a 68-year-old female who presented to the emergency department with abdominal pain and was subsequently diagnosed with disseminated herpes zoster and found to have underlying monoclonal gammopathy.

1. Introduction

Herpes zoster, also known as shingles, is caused by reactivation of latent varicella zoster virus (VZV) in the sensory ganglia. Herpes zoster rash typically manifests as clusters of painful vesicular rash affecting one side of the thoracic dermatome or on the face that does not cross the midline.1 Patients can experience prodromal sensory phenomena, nonspecific headache, photophobia, or malaise several days before the rash appears. The vesicular rash will progress for 3–5 days then gradually scabs over in 2–4 weeks.2 Disseminated VZV is defined by; generalized cutaneous eruptions in 2 or more continuous dermatomes; 20 or more cutaneous lesions outside of primary affected dermatome; or visceral organ involvement.1 Disseminated VZV infection poses a challenging and rare diagnostic dilemma, often only considered after the characteristic rash manifests days later. Through the case described below, we aim to shed light on the typical presentation of this uncommon disease. Here we report a case, where a painful gastrointestinal disorder (“enteric zoster”) was the initial presentation of the disseminated VZV infection, in a patient who was later found to have underlying monoclonal gammopathy.

2. Case presentation

A 68-year-old female presented to the emergency department with crampy lower abdominal pain, subjective fever, non-bloody non-bilious emesis, and severe non-bloody watery diarrhea for a duration of 2 days. She was initially treated symptomatically for viral gastroenteritis and discharged the same day. However, she later re-presented due to persistent severe abdominal pain. Medical history was notable for suspected chronic pancreatitis, peptic ulcer disease, congestive heart failure, chronic obstructive pulmonary disease, opioid use disorder (in remission) and hypertension. The patient’s home medications included, atorvastatin, albuterol-ipratropium, budesonide-formoterol, buprenorphine-naloxone, furosemide, nifedipine, omeprazole and ondansetron. The patient denied any sick contacts, denied any travel history or change in diet and denied any recent antibiotic use. The patient had no known diagnosis of HIV, diabetes or active malignancy, however, was not up to date with age-appropriate cancer screening and was not currently taking any immunosuppressive medication.

On presentation to the emergency department, the patient was afebrile and hemodynamically stable. Initial abdominal examination demonstrated diffuse pain across the lower abdominal quadrants with absence of any signs of an acute abdomen and no notable rash. Laboratory work was notable for acute kidney injury with serum creatinine of 1.94 mg/dL which was increased from a baseline creatinine of 0.7 mg/dL (reference range 0.5–0.8 mg/dL), alongside leukocytosis of 19.7 k/uL (reference range 4.00–10.80 k/uL) with neutrophilic predominance of 90 % (reference range 45–75 %), with normal liver function tests and normal serum lipase. Computed tomography (CT) imaging of the abdomen revealed wall thickening within the terminal ileum and ascending colon suggesting terminal ileitis and ascending colitis (Fig. 1). Stool studies were sent, and the patient was started on ciprofloxacin and metronidazole for presumed bacterial colitis. Her diarrhea resolved prior to antibiotic administration and infectious stool workup was negative.

Fig. 1.

CT with contrast of abdomen and pelvis revealed wall thickening in a terminal ileal loop of small bowel within the pelvis, suggested terminal ileitis.

On day 2 of hospital stay, the patient developed acute neuropathic pain in her left lower extremity which she described as an ‘electric shock’ and severe hyperesthesia over her left ilioinguinal region with light palpation causing excruciating pain alongside associated weakness in left sided hip flexion. Magnetic resonance imaging (MRI) of the spine showed no acute cord compression or other abnormality. Gabapentin 200 mg twice daily was started for the neuropathic pain. The patient had persistent abdominal pain with left lower extremity neuropathy and on day 3 of hospitalization developed acute encephalopathy of unclear etiology, tremor, neck stiffness and headache. CT imaging of the head was unremarkable for any acute event, and spot electroencephalogram was negative for seizure activity however, demonstrated diffuse slowing in keeping with encephalopathy. Lumbar puncture was not available.

Acute encephalopathy resolved upon discontinuation of gabapentin and on day 8 of hospitalization the patient developed a vesicular burning painful rash affecting multiple dermatomes (C3, T11-12, S1-2) on her left side with the rash not crossing the midline. Serum VZV PCR (Polymerase Chain Reaction) was positive confirming the diagnosis of disseminated VZV infection, the patient was managed with a 10-day course of Valacyclovir 1g tablets three times a day with resolution of the rash. The patient was also managed for post herpetic neuralgia with gabapentin.

Given her renal injury, polyuria, hyponatremia, and mild proteinuria alongside developing disseminated VZV infection, malignancy workup was undertaken including serum electrophoresis, which demonstrated an IgG-Lambda monoclonal protein on immunosubtraction study, Ig G 1687, with k/L ratio 1.67, indicating an underlying diagnosis of monoclonal gammopathy. HIV infection was excluded.

3. Discussion

This case highlights two key learning points, firstly the complex nature and diagnostic challenges of disseminated VZV, this patient suffered from abdominal pain, acute encephalopathy, and primary motor neuropathy, all of which were likely related to disseminated VZV infection, but all of which preceded the characteristic rash associated with VZV. Secondly, the importance of searching for underlying malignancy in disseminated VZV.

Herpes zoster is normally uncomplicated, self-limiting, and easily preventable by routine vaccination. 1 However, in a small proportion of the population, typically immunocompromised patients, reactivation of VZV is not simply a benign infection and can lead to multiple complications ranging from post herpetic neuralgia to disseminated VZV, visceral involvement, pneumonia, encephalitis and in some extreme cases death.2

Visceral VZV infection is a challenging diagnosis to establish. Just as in the case reported above, patients typically present with gastrointestinal symptoms including abdominal pain typically refractory to analgesia which in some cases can mimic an acute abdomen,3–6 alongside other symptoms including nausea, vomiting and diarrhea.4 The diagnosis is challenging. Firstly, in most cases of visceral VZV, abdominal pain and visceral signs precede the characteristic rash.7 Secondly, given the vast range of differential diagnosis for abdominal pain alongside commonly unremarkable radiologic imaging in cases of visceral VZV, the diagnosis is typically only arrived at once dermatologic signs are present,4 as in the case above.

Some reported cases of visceral VZV have documented isolated CT findings of peri-arterial adipose tissue stranding around the superior mesenteric vein and celiac arteries,7–9 although peri-arterial fat stranding can be seen in several etiologies, in the right clinical setting this could provide a useful diagnostic clue for the consideration of visceral VZV. In the case mentioned above, CT imaging demonstrated inflammation of the gastrointestinal tract with no evidence of fat stranding. It is unclear the significance of this finding in the overall case. Given the negative infectious stool workup and exclusion of other differentials, the colitis could have been the early sign of visceral involvement of VZV. One case series has hypothesized the role of positive VZV PCR in serum and feces as a way of detecting visceral VZV in the absence of cutaneous involvement,10 however this requires early clinical suspicion of visceral VZV.

VZV encephalitis is a rare complication of disseminated VZV infection, occurring in only 0.1–0.2 % of such cases.11 Advanced age is recognized as the most significant risk factor.12 In the case presented, the patient exhibited altered mental status and encephalopathy which was attributed to acute illness encephalopathy vs adverse side effects to gabapentin, given its quick resolution prior to treatment with valacyclovir. However, due to the absence of an MRI brain imaging and lumbar puncture with cerebrospinal fluid analysis, a definitive diagnosis of VZV encephalitis could not be excluded.

Disseminated VZV infection mainly affects immunocompromised patients, in particular transplant patients and patients with hematologic malignancies, 4 although there have been a few isolated cases reported in an immunocompetent host.13 In the above-described case, given the strong correlation between immunocompromised host and developing disseminated VZV, along with the association of disseminated VZV as a predictor of underlying malignancy.14 Further workup was undertaken which revealed underlying monoclonal gammopathy in this patient. Unfortunately, upon discharge the patient was lost to follow up and further medical workup of the etiology of the patient’s monoclonal gammopathy alongside age-appropriate cancer screening could not be achieved.

4. Conclusions

The presenting case depicted an unusual clinical course of disseminated herpes zoster. It started from enteric zoster, along with primary motor neuropathy and dysautonomia, and suspected meningeal involvement prior to skin manifestations. Prodromal symptoms in herpes zoster can be various and lead to misdiagnosis. Hence, it is crucial for clinicians to recognize the uncommon presentations of common diseases and consider hypothesis beyond the usual suspects. Further research and case reporting are essential to educate medical providers about the disease patterns associated with disseminated VZV. Additionally, this case underscores the importance for clinical practitioners to diligently investigate potential underlying malignancies when encountering an immunocompetent patient exhibiting disseminated herpes zoster.