A kidney transplant recipient with labial cellulitis and multiple skin lesions

Case Report: A kidney transplant recipient with labial cellulitis and multiple skin lesions
 
Final Diagnosis:
Protothecosis
 
Brief history of the Present Illness:
A 49 year old female presented with a two day history of left groin pain. She initially developed a “pinpoint” red spot on her left labium. This spot started to drain purulent fluid and then progressed to swelling, pain, and redness of her entire left labium. She had associated subjective fevers and shaking chills. Additionally, two weeks prior, she developed two painful blisters on her left lower extremity and one on her right breast. These had started to drain purulent fluid as well.
 
Past Medical History including allergies (if relevant):
She had a history of type 1 diabetes complicated by diabetic nephropathy. She underwent a kidney transplant 9 years prior. She also had a history of Streptococcus agalactiae endocarditis, requiring bioprosthetic mitral valve replacement three years prior. Subsequently, she developed Methicillin resistant Staphylococcus aureus endocarditis of her bioprosthetic mitral valve, which required repeat valve replacement. She had also had a hysterectomy.
 
Key Medications (if relevant):

• Trimethoprim/sulfamethoxazole for Pneumocystis prophylaxis


• Tacrolimus


• Mycophenolate

 
Epidemiological history (if relevant, such as habits, social and family history, animal exposures or travel:
She had no pets at home and had not been sexually active for several years. She denied any recent travel, and she was born/raised in a midwestern U.S. state.  She had not gone swimming or had any exposure to fresh water rivers, ponds, or lakes.  She had not been hiking or participated in any gardening.
 
Physical Examination:
The patient appeared lethargic and intermittently developed rigors. Her temperature was 102°F (38.9°C), blood pressure 144/75 mm Hg, pulse 110 beats per minute, respirations 18 breaths per minute, oxygen saturation 99% on room air. She had 2+ pitting edema of her lower extremities bilaterally. There was a 1.5 cm oval healing erosion on her right inferomedial breast. There were two round, well-demarcated erosions on her left lower extremity. The left labium was edematous, indurated, erythematous, and tender to palpation. On the left labium there was a 5mm oval erosion. The rest of the examination was normal. Please refer to figures #1, 2, and 3 for physical exam findings.
 
Studies:
The white blood cell count was 11.5 K/UL (reference range 3.5 – 10.5 K/UL) with a neutrophil predominance of 71%. The glucose was 241 mg/dL (reference range 65 – 100 mg/dL) and the rest of the basic metabolic panel was normal. The liver function tests were normal. A CT scan of the pelvis showed soft tissue stranding and nodularity of the left labium, likely representing cellulitis, without a discrete fluid collection (Figure #4)
 
Clinical Course Prior to Diagnosis (if relevant): Note Figures if appropriate
She was empirically started on IV vancomycin and piperacillin/tazobactam. Despite broad spectrum antibiotics, she continued to have fevers as high as 103°F (39.4°C) as well as rigors for several days. Dermatology was consulted and biopsied the right breast lesion and a left lower extremity lesion. These specimens were sent for pathology and bacterial/fungal cultures. While awaiting her biopsy results, her left labium became more indurated and painful. A repeat CT pelvis showed increased nodularity and increased fat stranding with extension in to the mons pubis (Figure #5). Multiple sets of routine blood cultures showed no growth. She progressively became more ill appearing and clinically worsened.
 
Differential Diagnosis

1. Fusariosis


2. Candidiasis


3. Histoplasmosis


4. Blastomycosis


5. Protothecosis

 
Diagnostic Procedure(s) and Result(s)
Biopsies of her right breast and left lower extremity lesions were performed (Figures #6 & 7). These showed large yeast-like forms with many smaller internal spherules. The yeast-like forms resembled a floret-like or soccer ball appearance, and they measured approximately 10-20 micrometers. A multi-disciplinary meeting was held between Infectious Diseases, Dermatology, and Pathology. It was deemed that the biopsy specimens were most consistent with Prototheca.
 
Unfortunately, microbiologic confirmation could not be obtained via culture growth. All other etiologies were ruled out based on biopsy appearance, organism size, and non-invasive testing (i.e. negative urine Histoplasma and Blastomyces antigens). 18S and 28S rRNA sequencing later came back negative for fungus as well. 
 
Treatment/Follow-up
She was started on IV liposomal amphotericin B for treatment of protothecosis. Within 24 hours, her fevers/rigors resolved and over a few days she significantly improved. The lesions on her right breast and left lower extremity completely resolved. Her left labial cellulitis completely resolved as well. She was treated with approximately 4 weeks of IV liposomal amphotericin B and then transitioned to three months of oral itraconazole 200mg twice daily. She completed this therapy with no recurrence of her infection.
 
Brief Discussion of Differential/Major Teaching points of case:
Prototheca are algae which are distributed worldwide. They are often, however, misidentified as yeasts in tissue and culture. The most common source of protothecal infection is usually traumatic inoculation from contaminated soil or water. Immunocompromised hosts are generally the most susceptible, including those with organ transplantation, hematologic malignancy, or receiving corticosteroid therapy. The two most common species that cause disease in humans are Prototheca wickerhamii and Prototheca zopfii.
 
Protothecosis generally manifests in three clinical forms. The most common is cutaneous disease with single or multiple vesiculobullous/ulcerative lesions with purulent drainage. The second form is olecranon bursitis, which usually occurs in immunocompetent patients in the setting of trauma to the elbow or a surgical wound. The final and most severe form is disseminated protothecosis in which multiple sites can be involved, including skin, peritoneum, meninges, spleen, and blood.  Diagnosis is made via biopsy through histology and culture. Organisms can be visualized on Gomori methenamine silver or periodic acid-Schiff stain, often seen as multiple endospores within a sporangia. The mainstay of treatment for protothecosis is IV amphotericin B, however azoles have been shown to be effective as well, particularly ketoconazole, itraconazole, and fluconazole.
 
Final Diagnosis:
Protothecosis
 
References

1. Lass-Florl C, Mayr A. Human protothecosis. Clinical Microbiology Reviews. 2007;20(2):230. PMID 17428884.


2. Mayorga J, Barba-Gomez JF, Verduzco-Martinez AP, et al. Clinics in Dermatology. 2012;30(4):432. PMID 22682193.

 
Images
Figure #1: Physical exam photo of lower extremities
Figure #2: Physical exam photo of right breast
Figure #3: Physical exam photo of left labium
Figure #4: CT scan of Pelvis
Figure #5: Repeat CT Pelvis
Figure #6: Left lower extremity biopsy, periodic acid-Schiff-diastase stain, 40x magnification
Figure #7: Left lower extremity biopsy, periodic acid-Schiff-diastase stain, 100x magnification