June 2012 Pulmonary Case of the Month: What’s a Millet Seed Look Like?

Alexis Christie, MD

Robert Viggiano, MD

Lewis J. Wesselius, MD

Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 32 year old woman presents with a week long history of dyspnea, cough, fatigue, tiredness and pruritis. She has a past medical history (PMH) of Stage IIB, nodular sclerosing Hodgkin’s disease diagnosed in January, 2011. She underwent several cycles of chemotherapy and eventually an autologous stem cell transplant in January, 2012. Her current medications include:

• Acyclovir 800mg bid
• Ativan 0.5mg q4h/ prn
• Hydromorphone 8mg q4h/ prn
• Atarax 100mg q6h/ prn
• Compazine 10mg q6h/ prn

She had just finished a course of levofloxacin.

PMH, SH and FH

As above. She is a life-long nonsmoker and has no history of lung disease.

Physical Examination

Her physical examination was normal.

Chest X-ray

Her chest x-ray was interpreted as unchanged from previous examinations. 

Which of the following are indicated?

1. Thoracic CT scanning
2. PET scanning
3. Empiric treatment with broad spectrum antibiotics
4. All of the above

Reference as: Christie A, Viggiano R, Wesselius LJ. June 2012 pulmonary case of the month: what's a millet seed look like? Southwest J Pulm Crit Care 2012;4:182-8. (Click here for a PDF version of the case)

May 2012 Pulmonary Case of the Month: Things Are Not Always as They Seem

Lewis J. Wesselius, MD

Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 69 year old woman was seen for side effects of corticosteroids. She is a winter visitor to Arizona. She was hospitalized in March 2008 with increased dyspnea and cough and had an abnormal CT chest. A VATS lung biopsy was performed. The pathology of the lung biopsy interpreted as bronchiolitis obliterans. She was started on prednisone 60 mg/day.

Subsequently, she returned to Minnesota and was seen by rheumatologist with a diagnosis made of possible rheumatoid arthritis. She was treated with methotrexate (12.5 mg weekly) and continued prednisone at 20 mg/day from 2008 to 2011.  At that time a question was raised of methotrexate lung toxicity and it was stopped but she continued on prednisone 20 to 40 mg/day.  She is currently having issues with steroid side effects and seen for a second opinion.

PMH, SH and FH

She has a history of knee and other joint pains.  She had knee replacement surgery in Jan 2008 with worsening of her dyspnea and cough.  She has a history of diabetes which was apparently induced by the corticosteroids. Her current medications include prednisone 20 mg/day, insulin, metformin, lovastatin. She is a former smoker with 25 pack-years but quit 25 years ago. She has no family history of lung disease.

Physical Examination

She was an obese woman appearing somewhat Cushingoid in no acute distress. On chest auscultation she had diminished breath sounds but no crackles or wheezes. Examination of her joints revealed no abnormalities. The remainder of her physical examination was normal.

Chest X-ray

Her chest x-ray was interpreted as normal.

Which of the following are indicated?

1. Pulmonary function testing
2. Pulmonary CT scanning
3. Rheumatologic evaluation
4. Repeat of open lung biopsy
5. All of the above

Reference as: Wesselius LJ. May 2012 pulmonary case of the month: things are not always as they seem. Southwest J Pulm Crit Care 2012;4:142-8. (Click here for a PDF version of the case)

April 2012 Pulmonary Case of the Month: Could Have Fooled Me!

Bridgett A. Ronan, MD

Robert Viggiano, MD

Lewis J. Wesselius, MD

Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 60 year old man was seen by his primary care physician with cough for 2 weeks which was dry and worse with deep breathing. He had been exposed to smoke from industrial storage fire just prior to the onset of his cough. He had developed fever for the past 3 days.

PMH, SH and FH

He has a history of osteopenia and was found to have a +PPD in high school for which he was never treated with isoniazid. Originally from New York he has lived in Arizona for 14 years. He was a former smoker having a 45 pack-year history having quit in 2007. He drives a delivery truck. His sister had tuberculosis which was treated and his father has emphysema.

Physical Examination

He had mild rhonchi in the right upper lung field. Otherwise, the physical exam was unremarkable.

Laboratory and Chest X-ray

A CBC was performed which revealed a hemoglobin of 11.7 g/dL, white blood cell (WBC) count of 11.9 X 1000 cells/ml with 79% neutrophils, and a platelet count of 337 X 1000/mL. Coccidioidomycosis serologies were drawn. A chest x-ray was taken (Figure 1).

Figure 1. Chest x-ray taken by the patient’s primary care physician which shows bilateral lung consolidations with multiple poorly defined bilateral lung nodules.

Considerations at this point include:

1. Community acquired pneumonia
2. Coccidioidomycosis
3. Tuberculosis
4. Pneumonitis from smoke inhalation
5. Pulmonary embolism
6. All of the above

Reference as: Ronan BA, Vigianno R, Wesselius LJ. April 2012 pulmonary case of the month: could have fooled me! Southwest J Pulm Crit Care 2012;4:122-9. (Click here for a PDF version of the case)

Pulmonary Nodules with Cutaneous Manifestations: A Case Report and Discussion

Christopher Strawter, MD

Pedro Quiroga, MD

Syed Zaidi, MD

Thomas Ardiles, MD

Maricopa Medical Center

Phoenix, Arizona

Abstract

The differential diagnosis of multiple pulmonary nodules is large and includes congenital and inherited disorders, malignancy, infectious etiologies, noninfectious granulomatous and inflammatory conditions,among many others. Diagnostic evaluation is aided by attention to extrapulmonary symptoms and features. We herein describe an unusual case of multiple pulmonary nodules attributed to cysticercosis and present a discussion of pathophysiologic changes related to medications and highlight the diagnostic value of extrapulmonary cutaneous features.

Case Report

History of Present Illness

A 31-year-old incarcerated Hispanic male presented with a nonproductive cough for several months and one episode of blood tinged sputum.  He admitted to weight loss and night sweats, headaches, and visual disturbances.  He was an immigrant from Honduras and lived in Arizona for the past 15 years.  He had chronic hepatitis C infection and was receiving treatment with pegylated interferon-alfa-2a (IFN-α) and ribavirin. His symptoms began one month after initiating antiviral therapy.

Physical Exam

On admission, his vital signs were stable.  Several mobile one cm cutaneous and subcutaneous nodules were palpable on the trunk and neck. Lymphadenopathy was not present.  The neurological exam revealed diplopia upon lateral gaze. The cardiopulmonary exam was unremarkable. 

Laboratory Data

Routine hematology work-up revealed leukopenia (2.3 x 10³/µL), neutropenia (1.4 x 10³/µL) without eosinophilia.  AST and ALT were 239 U/L and 265 U/L respectively. Quantiferon TB and coccidioidomycosis tests were negative.

Radiology

Plain radiograph of the chest was unremarkable.   Computed Tomography (CT) of the chest demonstrated multiple bilateral well defined nodules ranging in size from 7.2 mm to 11mm in diameter involving lung parenchyma and chest wall soft tissue structures (Figure 1). 

Figure 1. Computed tomography (CT) chest lung window.  Seen here are multiple, bilateral, well defined nodules involving the lung parenchyma and subcutaneous tissue.

MRI of the brain showed extensive bilateral T2 hyperintense and peripherally enhancing foci within the cerebrum, cerebellum and extraocular muscles consistent with the vesicular stage of neurocysticercosis (Figure 2). 

Figure 2. MRI brain.  Extensive bilateral T2 hyperintense and peripherally enhancing foci within the brain parenchyma and extraocular muscles consistent with the vesicular stage of neurocysticercosis (A). The scolex can be visualized within the cyst as a high intensity nodule giving the lesion a pathognomonic ‘hole-with-dot’ appearance (B).

Histopathology

Bronchoscopy revealed normal airways with negative bronchoalveolar lavage.  Histopathology from a needle core biopsy of a chest wall nodule revealed a cystic wall structure, consistent with cysticercosis (Figure 3).

 

Figure 3. Stained microsection of a chest wall needle core biopsy showing the cystic wall structure of cysticercosis. The wall consists of 3 layers: an outer or cuticular layer, a middle cellular layer and an inner fibrillary layer.

Percutaneous lung nodule biopsy demonstrated nonspecific necrotic granulomatous tissue. 

Hospital Course

On the basis of neuroimaging and subcutaneous biopsy findings, a diagnosis of disseminated cysticercosis with pulmonary involvement was made and the patient was started on a 28-day course of albendazole therapy.  One month follow-up revealed resolution of respiratory symptoms. Repeat CT chest, 53 days post-hospitalization revealed a regression in the magnitude of the pulmonary nodules, the largest now measuring 6mm in diameter (Figure 4). 

Figure 4. CT scans of the chest, lung windows. Comparing Panel A with Panel B performed 53 days later reveals a reduction in the size of the bilateral pulmonary nodules (arrows) after a 28-day course of anti-parasitic therapy with albendazole.

Regression of the pulmonary nodules was consistent with the diagnosis of pulmonary cysticercosis, in line with previous reports (1).

Discussion

The differential diagnosis of multiple pulmonary nodules is large. A variety of pulmonary disorders may affect both cutaneous and subcutaneous tissues and the lung (Table 1).

The findings of extrapulmonary nodules in other organ systems and biopsy of nodules can help establish the diagnosis or limit the differential diagnosis of multiple pulmonary nodules when thoracic image findings are nonspecific.

Cysticercosis refers to infection by the larval stage of the pork tapeworm, Taenia solium.  Cysticercosis has emerged as a cause of severe neurologic disease in the United States that primarily affects immigrants from endemic regions.  Within the US cases of cysticercosis are mostly reported in CA, IL, OR, TX, and NY.  Disseminated cysticercosis is an uncommon manifestation of the disease with fewer than 50 cases described worldwide, most occurring in India.  Even more unusual is involvement of the lung parenchyma (1), with less than 10 cases described in literature.  To our knowledge, this is only the second case of disseminated cysticercosis with pulmonary involvement described in North America (2). 

Cysticercosis most commonly affects the central nervous system (neurocysticercosis). However, when disseminated, it frequently involves the skin and subcutaneous tissue.  Cutaneous cysticerci are often a clue to the involvement of internal organs.  In one case series of thirty-three patients with disseminated cysticercosis, sixteen (48%) presented with cutaneous lesions (3).  Detection of the parasite in a biopsy specimen of skin nodules will aid in the diagnosis of disseminated cysticercosis and may prevent further, unnecessary diagnostic tests from being performed.

Sarcoidosis is a common cause of pulmonary nodules with extrapulmonary manifestations.  Recent reports have characterized the development of sarcoidosis in patients receiving pegylated interferon alfa and ribavirin for the treatment of Hepatitis C (4).  In sarcoidosis, there is a predominance of Th1 type immune response, while Th2 lymphocytes are relatively inactivated in granuloma formation (5).  Both IFN-α and ribavirin stimulate the differentiation of Th1-type lymphocytes while inhibiting the activation of Th2-type lymphocytes (6).  Together, this combination therapy works in favor of granuloma formation and the activation/re-activation of sarcoidosis. The temporal association between the initiation of therapy for hepatitis C and the onset of symptoms in the above case raised concern for drug induced sarcoidosis.  However, sarcoidosis is a diagnosis of exclusion and the specific identification of the parasite in the subcutaneous nodule biopsy makes sarcoidosis unlikely. 

The skin is the most common site for disseminated coccidioidomycosis.  Multiple pulmonary nodules with cutaneous lesions in an individual living in Arizona should raise suspicion for coccidioidomycosis. The above patient had a negative coccidioidomycosis work-up and biopsies were not consistent with that of coccidioidomycosis.

Conclusion

Pulmonary cysticercosis is an uncommon manifestation of cysticercosis.  The differential diagnosis of multiple pulmonary nodules is large. However, the diagnosis may be aided by recognizing extrapulmonary lesions that are often associated with lung diseases.  Disseminated cysticercosis with pulmonary involvement should be suspected in any patient presenting with multiple pulmonary nodules who is an immigrant from an endemic region or an individual who has resided in one of the States where cysticercosis is most commonly encountered.

References

1. Mamere AE, Muglia VF. Disseminated Cysticercosis With Pulmonary Involvement. J Thorac Imaging 2004;19:109-111.
2. Walts AE, Nivatpumin T, Epstein A. Pulmonary cysticercus. Mod Pathol 1995;8:299-302
3. Arora PN, Sanchetee PC, Ramakrishnan KR, Venkataram S. Cutaneous, mucocutaneous and neurocutaneous cysticercosis. Indian J Dermatol Venereol Leprol 1990;56:115-8
4. Ramos-Casals M, Mana J, Nardi N et al. Sarcoidosis in patients with chronic hepatitis C virus infection: analysis of 68 cases. Medicine 2000;84:69-80.
5. Rodríguez-Lojo, M. Almagro, J. M. Barja, et al., “Subcutaneous Sarcoidosis during Pegylated Interferon Alfa and Ribavirin Treatment for Chronic Hepatitis C,” Dermatology Research and Practice, vol. 2010, Article ID 230417, 2010. doi:10.1155/2010/230417
6. Tam RC, Pai B, Bard J, et al. Ribavirin polarizes human T cell responses towards a type 1 cytokine profile. J Hepatol 1999;30:376-382.

Address inquires to: Christopher.Strawter@mihs.org

Reference as: Strawter C,  Quiroga P, Zaidi S, Ardiles T. Pulmonary nodules with cutaneous manifestations: A  case report and discussion. Southwest J Pulm Crit Care 2012;4:116-21. (Click here for a PDF version of the manuscript)

March 2012 Pulmonary Case of the Month: There’s Air in There

Alexis Christie, MBBS

Lewis J. Wesselius, MD

History of Present Illness

A 40 year old male was seen with a one week history of dyspnea, dry cough, weakness and abdominal pain. He has a history of acute myelogenous leukemia (AML) diagnosed in December, 2010. He underwent consolidation chemotherapy but had a complication of acute lung injury following chemotherapy thought either to be due to infection or ara-C lung toxicity. Bronchoalveolar lavage was negative and video-assisted thoracotomy revealed only organizing pneumonia.

He underwent stem cell transplantation in May 2011 from a hepatitis C +, allogenic bone marrow transplant and received lamivudine post transplant because of the hepatitis C. Unfortunately, bone marrow biopsy in June 2011 revealed recurrent AML He received two cycles of decitabine.

He had further complications of severe graft versus host disease affecting his eyes, mouth and liver and severe, recurrent C. difficile sepsis. Present medications included: co-trimoxazole (Bactrim), lamivudine, acyclovir, posaconazole, tacrolimus, and prednisone.

Physical exam

Physical exam revealed a thin, moderately short of breath man but was otherwise unremarkable.

Radiology

His chest X-ray (Figure 1) and selected images from his CT scan (Figure 2) are shown below:

Figure 1. Chest x-ray.

Figure 2. Thoracic CT scan. Lung windows.

In addition to the confluent areas of airspace and ground glass opacities throughout both lungs what other finding is present?

1. Enlarged mediastinal lymph nodes
2. Pneumothorax
3. Atelectasis of the left lower lobe
4. Pneumomediastinum
5. Large RLL lung mass

Reference as: Christie A, Wesselius LJ. March 2012 pulmonary case of the month: there's air in there. Southwest J Pulm Crit Care 2012;4:88-93. (Click here for a PDF version of the case presentation)