Medical Image of the Week: Erythema Nodosum

Figure 1. Panel A: photograph of legs at initial presentation. Panel B: 2 weeks later.

A healthy 43-year-old woman presented to the emergency room with one day of diarrhea, vomiting and severe left-sided pleuritic chest pain. Chest radiography revealed an infiltrate in the left lower lobe with a small pleural effusion. White count was 14,000 cells/mcL. Eosinophil count was 2%. She was thought to have pneumonia and treated with azithromycin.

Two weeks later she returned to the emergency room with painful raised erythematous lesions on both lower extremities and generalized joint pain. A thoracic CT scan was performed showing left lower lobe pneumonia and small bilateral pleural effusions. Eosinophilia was 14%. She was diagnosed again as having pneumonia. There was no diagnosis made of the skin lesions. A cocci serology was drawn and sent to Davis California. She was given doxycycline.

Subsequently the cocci serology was found to be positive for IgG and IgM and negative for complement fixation antibodies. She was seen by her primary care physician who diagnosed acute coccidioidomycosis and started her on Diflucan 200 mg daily and referred her for consultation. At her first visit 6 weeks into her illness she was still complaining of arthralgias, fatigue and cough.

Physical examination was negative except for innumerable red raised lesions on her thighs and anterior surfaces of her legs with confluence at the ankles (Figure 1). One month after her initial visit her legs were much improved although there was some peeling of the skin and residual erythema of the lower extremities (Figure 2).

Erythema Nodosum (EN) is a panniculitis of subcutaneous fat which can be associated with a variety of conditions including streptococcal pharyngitis, tuberculosis, sarcoidosis, inflammatory bowel disease, cancer, or bacterial infections (1). The usual presentation of this disease is the presence of painful raised erythematous nodules symmetrically on the anterior surfaces of the lower extremities. These lesions do not represent sites of infection but are most likely a result of type IV delayed hypersensitivity.

EN was first described as a benign form of coccidioidomycosis in 1936, and was further characterized by Charles Smith in 1940 when he described acute coccidioidomycosis as an illness characterized by an “influenza like initial phase followed in 2 to 18 days by the eruptive phase of erythema nodosum lasting from six days to three weeks with pigmented areas lasting for months” (2). He noted that recovery was invariable. This was in a time where the frequent presentation of acute coccidioidomycosis as an inapparent infection was not known and the mortality of acute cocci was as high as 50%. Twenty years later, Smith and Pappagiannis made the observation that EN was 2 to 10 times more frequent in females than males (3). Braverman (4) in 1999 observed the protective effect of EN by reporting on 60 pregnant women with coccidioidomycosis. Thirty of these women with EN had no dissemination, and of the 30 without EN, 11 disseminated and one died. The mechanism of this protective effect has yet to be characterized.

Physicians living in the Southwest have learned that “the bumps” (EN), desert rheumatism (polyarthralgia), eosinophilia associated with a flulike illness, and acute knifelike pleuritic chest pain in an otherwise healthy person are all signs and symptoms which lead to a rapid diagnosis of coccidioidomycosis (5). Because of the time sequence of the appearance of EN in this illness this rash is often felt incorrectly to be an allergic reaction to antibiotics given for the previously diagnosed pneumonia. Even though EN is associated with many varied conditions, its presence in the Southwestern United States should lead the physician to consider coccidioidomycosis as the most likely diagnosis.

Gerald F. Schwartzberg, MD

HonorHealth Pulmonology

Phoenix, AZ USA

References

1. Blake T, Manahan M, Rodins K. Erythema nodosum - a review of an uncommon panniculitis. Dermatol Online J. 2014 Apr 16;20(4):22376. [PubMed]
2. Smith CE. Epidemiology of acute coccidioidomycosis with erythema nodosum ("San Joaquin" or "Valley Fever"). Am J Public Health Nations Health. 1940 Jun;30(6):600-11. [CrossRef] [PubMed]
3. Smith CE, Pappagianis D, Levine HB, Saito M. Human coccidioidomycosis. Bacteriol Rev. 1961 Sep;25:310-20. [PubMed]
4. Braverman IM. Protective effects of erythema nodosum in coccidioidomycosis. Lancet. 1999 Jan 16;353(9148):168. [CrossRef] [PubMed]
5. Stevens DA. Coccidioidomycosis. N Engl J Med. 1995 Apr 20;332(16):1077-82. [CrossRef] [PubMed]

Addendum: Another Erythema Nodosum

Figure 2. Another case of erythema nodosum.

While the above article was “in press”, another case of EN came into the office (Figure 2). Her history was similar to the first patient. Uncle Jun, the patriarch in the “Sopranos,” said in his heavy New York accent, “They come in threes.” Based on Uncle Jun, I am anticipating seeing another case of EN this week.

Gerald F. Schwartzberg, MD

HonorHealth Pulmonology

Phoenix, AZ USA

Cite as: Schwartzberg GF. Medical image of the week: erythema nodosum. Southwest J Pulm Crit Care. 2017;15(4):188-90. doi: https://doi.org/10.13175/swjpcc126-17 PDF 

Medical Image of the Week: Disseminated Coccidioidomycosis

Figure 1. Thoracic CT with diffuse bilateral ground glass opacities with extensive nodularity. Though present throughout all lobes, it is worse in the upper lobes.

Figure 2. Scattered papular lesions with biopsy positive for coccidioidomycosis spherules.

A 67-year-old African American man with no significant past medical history presented with shortness of breath and flu-like symptoms. On exam, he was noted to be profoundly hypoxemic with imaging showing diffuse thoracic changes (Figure 1) and a diffuse papular rash (Figure  2). Initial workup included coccidioidomycosis serologies which returned positive with a titer of 1:128.

While exposure to coccidioidomycosis is very common in southern Arizona, dissemination is a rare occurrence.  The incidence is estimated between 0.2 and 4.7 percent. Patients at highest risk include those that are immunosuppressed or that are of African or Filipino ancestry. Common extra-pulmonary sites include skin or subcutaneous tissue, meninges of brain or spinal cord, and bones. Even rarer sites include the eyes, liver, prostate, mediastinum, and kidneys. Treatment is usually the same as with pulmonary infection which is an azole agent. However, if the patient’s symptoms are severe or if the lesions involve the spine, amphotericin is recommended instead. Steroid use is controversial but may be beneficial in severe cases. Unfortunately, our patient did not respond to the combination of fluconazole plus amphotericin and succumbed to his severe disease.

Tiffany Ynosencio, MD

Division of Pulmonary, Allergy, Critical Care and Sleep

Banner-University Medical Center

Tucson, AZ USA

References

1. Crum NF, Lederman ER, Stafford CM, Parrish JS, Wallace MR. Coccidioidomycosis: a descriptive survey of a reemerging disease. Clinical characteristics and current controversies. Medicine (Baltimore). 2004 May;83(3):149-75. [CrossRef] [PubMed]
2. Adam RD, Elliott SP, Taljanovic MS. The spectrum and presentation of disseminated coccidioidomycosis. Am J Med. 2009 Aug;122(8):770-7. [CrossRef] [PubMed]
3. Galgiani JN. Manifestations and treatment of extrapulmonary coccidioidomycosis. UpToDate  Jan 02, 2017. Available at: http://www.uptodate.com/contents/manifestations-and-treatment-of-extrapulmonary-coccidioidomycosis (requires subscription).

Cite as: Ynosencio T. Medical image of the week: disseminated coccidioidomycosis. Southwest J Pulm Crit Care. 2017;14(2):65-6. doi: https://doi.org/10.13175/swjpcc011-17 PDF 

Medical Image of the Week: Bronchial Artery Embolization

Figure 1. Thoracic CT with contrast demonstrating right upper and lower lobe tree-in-bud and ground glass opacities (arrows) consistent with progressing pulmonary coccidioidomycosis.

Figure 2. Chest radiograph demonstrates the ethylene vinyl alcohol polymer retained in the bronchial arteries after the embolization procedure (arrows).

A 25-year-old woman with a past medical history significant for pulmonary coccidioidomycosis and poorly controlled type I diabetes mellitus presented to the emergency department with a chief complaint of 4 days of progressively worsening shortness of breath and 3-4 days of intermittent hemoptysis. Initial CT scan demonstrated progressive tree-in-bud and ground glass opacities in the right upper and lower lung lobes suggesting worsening of her ongoing coccidiomycosis (Figure 1). On hospital day 3 she began to have worsening hypoxemia and hemoptysis requiring transfer to the intensive care unit. Interventional radiology was consulted who performed an emergent right sided bronchial artery embolization with the ethylene vinyl alcohol polymer, Onyx^tm. After embolization her chest radiographs demonstrated evidence of the embolization material in the pulmonary vasculature (Figure 2).

Ethylene vinyl alcohol polymer, Onyx^tm is a liquid embolic substance which solidifies after contact with ionic materials (1). This results in a rapid, irreversible and permanent embolization of the bleeding target vessel (2). It was initially approved for use in the embolization of cerebral arteriovenous malformations, however has been used for rapid embolization of other hemorrhagic conditions such has hemoptysis from bleeding bronchial arteries (3). The most common complication after embolization is chest pain that is self-limiting. Transverse myelitis from spinal cord ischemia is the most serious complication associated with bronchial artery embolization however the occurrence is significantly decreased by spinal arterial identification during initial angiography (4). This patient’s embolization was without complications. She was successfully extubated on hospital day 15 without evidence of ongoing hemoptysis and will continue to follow up in the pulmonary and infectious disease clinics for ongoing treatment of her Coccidiodes pulmonary disease.

Benjamin J. Jarrett MD, MPH and Sachin Chaudhary, MD

Department of Medicine

University of Arizona

Tucson, AZ USA

References

1. Lubarsky M, Ray C, Funaki B. Embolization agents-which one should be used when? Part 2: small-vessel embolization. Semin Intervent Radiol. 2010 Mar;27(1):99-104. [CrossRef] [PubMed]
2. Yamashita K, Taki W, Iwata H, Nakahara I, Nishi S, Sadato A, Matsumoto K, Kikuchi H. Characteristics of ethylene vinyl alcohol copolymer (EVAL) mixtures. AJNR Am J Neuroradiol. 1994 Jun;15(6):1103-5. [PubMed]
3. Guimaraes M, Wooster M. Onyx (Ethylene-vinyl Alcohol Copolymer) in Peripheral Applications. Semin Intervent Radiol. 2011 Sep;28(3):350-6. [CrossRef] [PubMed]
4. Sopko DR, Smith TP. Bronchial artery embolization for hemoptysis. Semin Intervent Radiol. 2011 Mar;28(1):48-62. [CrossRef] [PubMed]

Cite as: Jarrett BJ, Chaudhary S. Medical image of the week: bronchial artery embolization. Southwest J Pulm Crit Care. 2016;13(1):32-3. doi: http://dx.doi.org/10.13175/swjpcc053-16 PDF

Medical Image of the Week: Cutaneous Coccidioidomycosis

Figure 1. Right distal anterior thigh. Fungal culture grew Coccidioides immitis from biopsy.

A 46-year-old Hispanic man with no known past medical history presents to his primary care physician for a progressively worsening “rash” located over his right thigh. Patient described the lesion as raised, scaly, and itchy. It has been “growing” for the past one year and started out as a small “pimple”. Patient denied any trauma to the effected region over this time period. Surgical history was significant for a splenectomy 15 years prior that was needed after a traumatic accident. He works in construction and lives in southern Arizona. He denied alcohol, tobacco and or illicit drug use. Patient has attempted to treat this skin lesion with over the counter hydrocortisone ointment with no relief. He denied any other associated symptoms including fever/chills, headache, vision changes, night sweats, weight loss, cough, shortness of breath, and or joint pains. Vital signs were stable upon presentation. Physical exam was entirely benign other than the isolated skin lesion shown above (Figure 1). It measured roughly 5cm at its greatest dimension and was located just superior the right knee on the anterior portion of the distal thigh. Nodularity was appreciated upon palpation but no tenderness was noted. Areas of erythema were non-blanching. Small satellite lesions were seen on the perimeter.

He was sent to a dermatologist and biopsies were performed. Light microscopy and culture confirmed the diagnosis of cutaneous coccidioidomycosis. Initial laboratory work revealed a normal complete blood count and complete metabolic panel. Serum coccidioides IgM antibody was negative but IgG was confirmed to be positive with a reflex complement fixation titer of 1:16. Chest X-ray was normal. Patient was started on oral fluconazole 400mg daily. Repeat coccidioides IgG titers decreased to 1:8 at a four- week follow-up. Patient has been tolerating the medication well and skin lesion has begun to regress.

Norman Beatty MD¹ and Mayar Al Mohajer MD²

¹Departments of Internal Medicine and ²Infectious Diseases

University of Arizona College of Medicine

Tucson, AZ

Cite as: Beatty N, Al Mohajer M. Medical image of the week: cutaenous coccidioidomycosis. Southwest J Pulm Crit Care. 2015;11(5):226-7. doi: http://dx.doi.org/10.13175/swjpcc110-15 PDF

Medial Image of the Week: Palmar Erythema Multiforme

Figure 1. Palmar rash in a patient with acute pulmonary coccidioidomycosis resembling erythema multiforme.

An 18 year-old male presented for evaluation of abnormal chest imaging. Prior to moving to Tucson, Arizona three weeks before presentation, he was diagnosed with ankylosing spondylitis and was started on adalimumab (Humira). Approximately one week prior to presentation he developed a fever and cough. Over 3-4 days the cough worsened and he developed a palmar rash (Figure 1). He was seen in the emergency department and was started on levofloxacin. Prior to presentation in the pulmonary clinic his rash had resolved but the cough had persisted. Chest imaging showed airspace opacities within the left upper lobe with associated small left pleural effusion. Bronchoalveolar lavage revealed 57% eosinophils. Fungal cultures, bacterial cultures, and cytology were non-diagnostic. Coccidioides IgG antibody was negative but Coccidioides IgM antibody converted to positive, suggesting acute infection. The patient was started on oral fluconazole and clinically improved. Erythema nodosum and erythema multiforme are noted in as many as 25 % of patients with acute pulmonary coccidioidomycosis. The rashes usually occur within a few days of infection and are considered a good prognostic sign (1).

Ryan Nahapetian, MD, MPH and Joshua Malo, MD

Pulmonary, Allergy, Critical Care, & Sleep Medicine

University of Arizona, Tucson, AZ

Reference

1. Smith JA, Riddell J 4th, Kauffman CA. Cutaneous manifestations of endemic mycoses. Curr Infect Dis Rep. 2013;15(5):440-9. [CrossRef] [PubMed]

Cite as: Nahapetian R, Malo J. Medical image of the week: palmar erythema multiforme. Southwest J Pulm Crit Care. 2015;11(5):217. doi: http://dx.doi.org/10.13175/swjpcc102-15 PDF

Medical Image of the Week: Fungus Ball

Figure 1. Panel A: Coronal view of thoracic CT scan shows a fungus ball (mycetoma) within a 4.7cm thin walled cavity, Panel B: Axial image of fungus ball and thin walled cavity.

Figure 2 Panel A. Prominent eosinophilic infiltration with epithelial-lined cavity containing fungus ball (orange arrow). Panel B: Higher magnification.

A 69 year-old Asian woman living in Arizona with a past medical history of nephrotic syndrome on high-dose steroids had worsening pulmonary symptoms. A computed tomography (CT) of the chest (Figure 1) showed a 4.7 cm thin walled cavitary lesion in the right middle lobe compatible with mycetoma. She underwent thoracotomy for mycetoma resection. Surgical pathology confirmed an epithelial-lined cavity containing dense mycelia (Figure 2). Given the patient lived in an endemic area; the cavity was thought to be likely due to coccidioidomycosis. However, the mycetoma was of unclear etiology. No spherules were noted on GMS stain and tissue culture was negative. While of unclear clinical significance which fungus colonizes a pre-existing cavity, a Coccidioides PCR was performed and no Coccidioides genes were amplified making a Coccidioides mycetoma very unlikely.

Pulmonary mycetoma or “fungus ball” consists of dense fungal elements and amorphous cellular material within a pre-existing pulmonary cavity. Classically presenting as an aspergilloma, other fungi can cause similar lesions. Patients with mycetoma rarely develop symptoms. When present, symptoms can include chest pain, cough, hemoptysis, fatigue, fever, or unintentional weight loss. If asymptomatic, no treatment is required. Surgical resection and/or embolization may be required in cases of severe symptoms including hemoptysis.

Scott Rosen MD, Bridget Barker PhD, Branden Larsen MD PhD, and Ishna Poojary MD

Department of Medicine and Pathology

University of Arizona Medical Center

Tucson, AZ

and

Tgen North

Flagstaff, AZ

References

1. Winn RE, Johnson R, Galgiani JN, Butler C, Pluss J. Cavitary coccidioidomycosis with fungus ball formation. Diagnosis by fiberoptic bronchoscopy with coexistence of hyphae and spherules. Chest. 1994;105(2):412-6. [CrossRef] [PubMed]
2. Sobonya RE, Yanes J, Klotz SA. Cavitary pulmonary coccidioidomycosis: pathologic and clinical correlates of disease. Hum Pathol. 2014;45(1):153-9. [CrossRef] [PubMed]
3. Sheff KW, York ER, Driebe EM, Barker BM, Rounsley SD, Waddell VG, Beckstrom-Sternberg SM, Beckstrom-Sternberg JS, Keim PS, Engelthaler DM. Development of a rapid, cost-effective TaqMan Real-Time PCR Assay for identification and differentiation of Coccidioides immitis and Coccidioides posadasii. Med Mycol. 2010;48(3):466-9. [CrossRef] [PubMed]

Reference as: Rosen S, Barker B, Larsen B, Poojary I. Medical image of the week: fungus ball. Southwest J Pulm Crit Care. 2015;10(4):182-3. doi: http://dx.doi.org/10.13175/swjpcc025-15 PDF

Medical Image of the Week: Coccidioidomycosis

Figure 1. Preoperative x-ray (Panel A) demonstrating a right upper lobe cavitary lesion. X-ray (Panel B) status post lobectomy.

Figure 2. Coronal (Panel A) and axial (Panel B) images from a chest CT further demonstrating a right upper lobe cavitary lesion.

Figure 3. The 200x magnification H&E image (Panel A) demonstrates one of the numerous granulomas seen in the lung specimen. A low magnification (40x) (Panel B) H&E image showing the granulomatous infection, prominent at the left, surrounded by a wall made up of collagen.

Figure 4. Two images, both at 400x magnification, are of GMS stained tissue.  Panel A shows the numerous branching hyphae of the lesion.  Panel B shows a granuloma with a central Coccidioides spherule, marked by the red arrow.

A 41-year-old Hispanic man with a history of uncontrolled type 2 diabetes and coccidioidomycosis, presented to the emergency department with a two year history of hemoptysis and recent onset lower chest pain. Patient was found to have a right upper lobe cavitary lesion on x-ray (Figure 1). Due to concern for pulmonary and pericardial tuberculosis the patient was placed on isolation, and QuantiFERON Gold testing, Coccidioides antibodies and computed tomography of the chest were ordered. At this time the patient revealed that he had taken only 30 days of treatment for his coccidioidomycosis 2 years ago due to his understanding this was the complete course. The CT (Figure 2) demonstrated an irregular, spiculated, and thin-walled right apical cavitary lesion with satellite nodules. QuantiFERON Gold testing and Coccidioides testing were both positive. Surgical resection was performed due to ongoing hemoptysis. The surgical specimen demonstrated hyphae (Figure 4A), a rare spherule (Figure 4B) and caseating granulomas (Figure 3) consistent with coccidioidomycosis. Acid-fast stains were negative. Indications for surgery in coccidioidomycosis are continued or progressing symptoms following 3 months of treatment, complications (such as rupture, pneumothorax or effusion), and large size of abscess (1,2).

Kareem Hassan BA, Spencer Paulson MD, Carlos Tafich Rios MD

Departments of Medicine and Pathology

University of Arizona 

Tucson, AZ

References

1. Jaroszewski DE, Halabi WJ, Blair JE, et al. Surgery for pulmonary coccidioidomycosis: a 10-year experience. Ann Thorac Surg. 2009; 88:1765-72. [CrossRef] [PubMed]
2. Galgiani JN, Ampel NM, Blair JE, et al. Coccidioidomycosis. Clin Infect Dis. 2005;41: 1217-23. [CrossRef] [PubMed]

Reference as: Hassan K, Paulson S, Rios CT. Medical image of the week: coccidioidomycosis. Southwest J Pulm Crit Care. 2014;9(2):128-9 . doi: http://dx.doi.org/10.13175/swjpcc106-14 PDF

Medical Image of the Week: Coccidioidomycosis Pneumothorax

Figure 1. Right-sided pneumothorax (A) with subsequent placement of pigtail catheter and re-expansion of right lung (B).  CT shows bilateral multifocal airspace consolidation with nodules and cavitary interstitial disease (C).

Figure 2. PAP stain (A) and GMS stain (B) demonstrating Coccidioidomycosis from BAL (magnification, 400x).

A 36-year-old man with AIDS and disseminated coccidioidomycosis presented with severe right chest pain, shortness of breath, and a right-sided pneumothorax on CXR. A pigtail catheter was placed with near resolution of the pneumothorax. A bronchoscopy with bronchoalveolar lavage revealed spherules on cytology as well as coccidioidomycosis on culture. No other pathogens were identified. The pigtail catheter was removed three days later with resolution of the pneumothorax.

Rupture of subpleural coccidioidomycosis cavity into the pleural space resulting in pyopneumothorax and/or bronchopleural fistula is rare with reported rates of 1.4 – 2.6% for cavitary lesions (1).  Despite antiretroviral therapy and an undetectable viral load, disease was unresponsive to fluconazole.  Therapy was subsequently initiated with amphotericin B lipid complex, which resulted in significant improvement of his disease.

Ishna Poojary MD,  Christopher Geffre MD PhD,  Tirdad Zangeneh DO MA and Janet Campion MD

University of Arizona Medical Center

Tucson, AZ

Reference

1. Tiu CT, Cook J, Pineros DF, Rankin LF, Lin YS, Ghitan M, Brichkov I, Shaw JP, Chapnick EK. Pneumothorax in a young man in Brooklyn, New York. Clin Inf Dis. 2011;53(12);1296-7. [CrossRef] [PubMed] 

Reference as: Poojary I, Geffre C, Zangeneh T, Campion J. Medical image of the week: coccidioidomycosis pneumothorax. Southwest J Pulm Crit Care. 2013;7(4):251-2. doi: http://dx.doi.org/10.13175/swjpcc140-13 PDF