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Treatment of oral ranula in HIV-positive patient

Published:April 05, 2020DOI:https://doi.org/10.1016/j.anl.2020.02.009

      Abstract

      HIV-associated salivary gland disease refers to the pathology in head and neck lesions such as ranula, salivary gland swelling, xerostomia, and benign lymphoepithelial cysts in the parotid gland. Here, we present a unique case of the ranula patient with HIV infection treated with OK-423 sclerotherapy. Case report: The patient was a 42-year-old Japanese male with a few months history of oral floor swelling. Computed tomography (CT) showed a low-density area limited within the right floor of the mouth. Magnetic resonance imaging (MRI) revealed a distinct T2-high intensity area localized on the same location. The puncture fluid was bloody mucus, and the cytology was no malignancy. We diagnosed a simple ranula. He was, however, found to be HIV-antibody positive at the examination before treatment by chance. He was referred to the department of infectious diseases and definitively diagnosed HIV infection by western blot. We chose OK-432 sclerotherapy because of its minimally invasive and the risk of HIV infecting medical staff. Two times OK-432 injection made the lesion disappear. Conclusion: The case indicated that OK-432 sclerotherapy could be effective for ranula related to HIV.

      Keywords

      1. Introduction

      During the AIDS (acquired immunodeficiency syndrome) pandemic, pathologies in head and neck lesions were reported in more than half of patients positive for HIV (human immunodeficiency virus) and in about 80% of patients with AIDS [
      • Mourad W.F.
      • Young R.
      • Kabarriti R.
      • Blakaj D.M.
      • Shourbaji R.A.
      • Glanzman J.
      • et al.
      25-Year follow-up of HIV-positive patients with benign lymphoepithelial cysts of the parotid glands: a retrospective review.
      ,
      • Burger-Calderon R.
      • Ramsey K.J.
      • Dolittle-Hall J.M.
      • Seaman W.T.
      • Jeffers-Francis L.K.
      • Tesfu D.
      • et al.
      Distinct BK polyomavirus non-coding control region (NCCR) variants in oral fluids of HIV- associated Salivary gland disease patients.
      . The salivary glands and the oral cavity were common sites of anatomical lesions as clinical manifestations of HIV infection, including salivary gland swelling, xerostomia, benign lymphoepithelial cysts in the parotid gland, and ranula. These are called “HIV-associated salivary gland diseases” [
      • Ebrahim S.
      • Singh B.
      • Ramklass S.S
      HIV-associated salivary gland enlargement: a clinical review.
      ,
      • Meer S
      Human immunodeficiency virus and salivary gland pathology: an update.
      .
      Surgery is generally used to treat ranula. However, non-surgical approaches, such as OK-432 sclerotherapy, have proved effective for HIV-negative ranula patients [
      • Ohta N.
      • Fukase S.
      • Ishida A.
      • Aoyagi M.
      • Suzuki Y
      Treatments of various otolaryngological cystic diseases by OK-4321.
      ,
      • Fukase S.
      • Inamura K.
      • Ohta N.
      • Aoyagi M
      Treatment of Ranula with intracystic injection of the streptococcal preparation Ok-432.
      ,
      • Kono M.
      • Takafumi S.
      • Harutsugi A.
      • On H.
      • Watanabe M.
      • Chikazu D
      Evaluation of OK-432 injection therapy as possible primary treatment of intraoral ranula.
      ,
      • Roh J.-L.
      Primary treatment of ranula with intracystic injection of OK-432.
      ,
      • Ohta N.
      • Fukase S.
      • Kusano Y.
      • Saito Y.
      • Tateda Y.
      • Ishida Y.
      • et al.
      Treatment of auricular hematomas by OK-432.
      ]. Here, we report a unique case of OK-432 sclerotherapy for ranula considered to be associated with HIV.

      2. Case report

      A 42-year-old Japanese male was admitted to our department with a few months’ history of oral floor swelling. Right sublingual swelling with a soft palpation and a bluish color was observed (Fig. 1). There were no other lesions or symptoms in the head or neck, including parotid or submandibular gland swelling or xerostomia. He had been treated for anemia and syphilis, but the details were unknown. Computed tomography (CT) showed lesions of a low-density area in the right oral floor (Fig. 2). Magnetic resonance imaging (MRI) also revealed a well defined lesion within the floor of the mouth on the right side with a lower intensity than brain parenchyma on T1-weighted imaging and a higher intensity on T2-weighted imaging (Fig. 2). Contrary to our expectation, the fluid within the punctured lesion was bloody mucus (Fig. 3), with a non-malignant cytology. These findings were consistent with the right simple ranula, and there was no evidence of its extending into the neck. The serological data showed serum WBC 7400/µL, RBC 3 620 000/µL, Hb 11.2 g/dL, Plt 234 000/µL, AST 27 IU/L, ALT 22 IU/L, LDH 222 IU/L, BUN 29 g/dL, Cre 1.04 mg/dL, HbA1c 6.6%, ProGRP 155.8 pg/mL (baseline 0–81), NSE 13.7 ng/mL (baseline 0–16.3), HBs-Ag < 0.05 IU/mL, HCV-Ab < 1.0 S/CO, and HIV-Ag/Ab positive.
      Fig 1
      Fig. 1The oral floor at the first visit: right sublingual bluish swelling with a soft palpation.
      Fig 2
      Fig. 2Computed tomography (CT) and magnetic resonance imaging (MRI) findings. CT showed a low-intensity area on the right floor of the mouth. MRI revealed higher intensity by T2-weighted imaging and lower intensity by T1-weighted imaging than brain parenchyma. Both indicated that the lesion was a cyst localized within the right oral floor, namely a simple ranula.
      Fig 3
      Fig. 3The lesion puncture fluid. Bloody mucus might be a characteristic observation of ranula associated with HIV.
      Before treatment, the patient was referred to the division of infectious diseases on suspicion of HIV infection and was found to have a history consistent with high-risk activity. He was positive for HIV antibody by western blot and was diagnosed with HIV infection.
      We chose OK-432 sclerotherapy because it is minimally invasive and minimizes the risk to medical staff of HIV infection. We punctured the cyst with an 18 G needle, aspirated 5 mL of bloody mucus, and injected OK-432 solution (5.0 KE/2 mL) through the needle. Following treatment, the patient had a mild inflammation and tenderness around the right oral floor and a fever that lasted for a few days. Three months after the injection, the ranula was reduced but not eliminated, so a second injection (3.0 KE/1.2 mL) was performed then. Two months after the second injection the lesion was eliminated (Fig. 4). One and half years later, the patient was in good clinical conditions without recurrence.
      Fig 4
      Fig. 4The oral floor after two injections with OK-432. The lesion has disappeared.

      3. Discussion

      Pathologies in head and neck lesions frequently occur in HIV-positive patients [
      • Mourad W.F.
      • Young R.
      • Kabarriti R.
      • Blakaj D.M.
      • Shourbaji R.A.
      • Glanzman J.
      • et al.
      25-Year follow-up of HIV-positive patients with benign lymphoepithelial cysts of the parotid glands: a retrospective review.
      ,
      • Burger-Calderon R.
      • Ramsey K.J.
      • Dolittle-Hall J.M.
      • Seaman W.T.
      • Jeffers-Francis L.K.
      • Tesfu D.
      • et al.
      Distinct BK polyomavirus non-coding control region (NCCR) variants in oral fluids of HIV- associated Salivary gland disease patients.
      ,
      • Ebrahim S.
      • Singh B.
      • Ramklass S.S
      HIV-associated salivary gland enlargement: a clinical review.
      ,
      • Meer S
      Human immunodeficiency virus and salivary gland pathology: an update.
      ,
      • Syebele K.
      • Munzhelele T.I.
      The anatomical basis and rational for the transoral approach during the surgical excison of the sublingual salivary gland for the management of plungiing ranula.
      ,
      • Mabongo M.
      • Buch B.
      • Ngwenya S.P
      Plunging ranula: an unusual multilocular presentation.
      ,
      • Syebele K.
      • Munzhelele T.I.
      The potential impact of highly active antiretroviral therapy on the treatment and epidemiology of ranula in human immunodeficiency virus-positive patients.
      ,
      • Syebele K.
      • Munzhelele T.I.
      Oral mucocele/ranula:another human immunodeficiency virus-related salivary gland disease?.
      ]. Salivary gland disease is a common manifestation of HIV infection, with a significant increase in prevalence over the last two decades. The term “HIV-associated salivary gland disease” is recently used to designate HIV infection with salivary gland swelling involving the parotid gland, with or without xerostomia, benign lymphoepithelial cysts, or ranula salivary gland swelling involving the parotid gland, with or without xerostomia, benign lymphoepithelial cysts, or ranula [
      • Mourad W.F.
      • Young R.
      • Kabarriti R.
      • Blakaj D.M.
      • Shourbaji R.A.
      • Glanzman J.
      • et al.
      25-Year follow-up of HIV-positive patients with benign lymphoepithelial cysts of the parotid glands: a retrospective review.
      ,
      • Burger-Calderon R.
      • Ramsey K.J.
      • Dolittle-Hall J.M.
      • Seaman W.T.
      • Jeffers-Francis L.K.
      • Tesfu D.
      • et al.
      Distinct BK polyomavirus non-coding control region (NCCR) variants in oral fluids of HIV- associated Salivary gland disease patients.
      ,
      • Ebrahim S.
      • Singh B.
      • Ramklass S.S
      HIV-associated salivary gland enlargement: a clinical review.
      ,
      • Meer S
      Human immunodeficiency virus and salivary gland pathology: an update.
      ,
      • Syebele K.
      • Munzhelele T.I.
      The anatomical basis and rational for the transoral approach during the surgical excison of the sublingual salivary gland for the management of plungiing ranula.
      ,
      • Mabongo M.
      • Buch B.
      • Ngwenya S.P
      Plunging ranula: an unusual multilocular presentation.
      ,
      • Syebele K.
      • Munzhelele T.I.
      The potential impact of highly active antiretroviral therapy on the treatment and epidemiology of ranula in human immunodeficiency virus-positive patients.
      ,
      • Syebele K.
      • Munzhelele T.I.
      Oral mucocele/ranula:another human immunodeficiency virus-related salivary gland disease?.
      ]. The prompt recognition is invaluable in the diagnosis and treatment of both the salivary gland diseases including ranula and HIV infection. Female predominance with no right or left sublingual region predilection was reported [
      • Syebele K.
      • Munzhelele T.I.
      The anatomical basis and rational for the transoral approach during the surgical excison of the sublingual salivary gland for the management of plungiing ranula.
      ]. The nature of the punctured fluids was usually whitely mucous in HIV-negative ranula. However, it was reported that the aspirate consisted of a thick, bloody fluid which tested positive for salivary amylase [
      • Mabongo M.
      • Buch B.
      • Ngwenya S.P
      Plunging ranula: an unusual multilocular presentation.
      ]. Our patient had a history of treatment for anemia, and the extracted mucus was also bloody. The color of the ranula in our case was bluish. These results may allow us to speculate that bloody mucous is not specific finding for HIV-associated salivary gland diseases, however ENT physician should take into consideration about HIV-associated salivary gland diseases in cases of ranula with bloody aspirate(s).
      Ranula is usually treated by surgical approaches, such as sublingual gland excision. However, surgery poses risks of infection and complications such as nerve injury, cyst recurrence, and cosmetic problems. Non-surgical treatments for ranula with HIV include sclerotherapy such as OK-432 therapy, and antiretroviral therapy (ART) for HIV infection. To our knowledge, there have been no reports of sclerotherapy for ranula associated with HIV infection.
      OK-432 sclerotherapy was first reported as a new treatment for lymphangioma in 1987 with promise as a first-line treatment [
      • Ogita S.
      • Tsuto T.
      • Takahashi T
      Intracystic injection of OK-432: a new sclerosing therapy for cystic hygroma in children.
      ]. OK-432, a lyophilized streptococcal preparation made from group A Streptococcus pyogenes incubated with penicillin, was originally developed as an immunotherapeutic agent for cancer. It is highly effective against cystic lesions in the head and neck, eliminating lesions in 80% of patients with otolaryngological cystic diseases and in 83% with plunging ranula [
      • Ohta N.
      • Fukase S.
      • Ishida A.
      • Aoyagi M.
      • Suzuki Y
      Treatments of various otolaryngological cystic diseases by OK-4321.
      ]. It is also simpler, easier, safer, and less invasive than surgical approaches. Thus, OK-432 therapy offers a substitute for surgical treatment in otolaryngological cystic diseases such as ranula [
      • Ohta N.
      • Fukase S.
      • Ishida A.
      • Aoyagi M.
      • Suzuki Y
      Treatments of various otolaryngological cystic diseases by OK-4321.
      ]. In our case, two injections 3 months apart eliminated the lesion. This result suggests that OK-432 therapy offers potential in ranula patients with HIV infection.
      ART is usually performed as a treatment for HIV infection, but it may not be effective for HIV-associated salivary gland diseases [
      • Syebele K.
      • Munzhelele T.I.
      The potential impact of highly active antiretroviral therapy on the treatment and epidemiology of ranula in human immunodeficiency virus-positive patients.
      ,
      • Syebele K.
      • Munzhelele T.I.
      Oral mucocele/ranula:another human immunodeficiency virus-related salivary gland disease?.
      . It is very effective for benign lymphoepithelial cysts, but it produces a limited response in ranula [
      • Syebele K.
      • Munzhelele T.I.
      Oral mucocele/ranula:another human immunodeficiency virus-related salivary gland disease?.
      ].
      In conclusion, although HIV-associated salivary gland disease is rare, it should be considered in the differential diagnosis of ranula.

      Declaration of Competing Interest

      The authors declare no conflict of interest.

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