J Clin Immunol (2015) 35:344–347 DOI 10.1007/s10875-015-0151-7
BRIEF COMMUNICATION
Common Variable Immunodeficiency and Pulmonary Amyloidosis: A Case Report Sevket Arslan & Ramazan Ucar & Dudu Mehmet Yavsan & Hasan Esen & Emin Maden & Ismail Reisli & Ahmet Zafer Calıskaner
Received: 26 December 2014 / Accepted: 4 March 2015 / Published online: 14 March 2015 # Springer Science+Business Media New York 2015
Abstract Common variable immunodeficiency is the most common symptomatic primary immune deficiency characterized by hypogammaglobulinemia, recurrent infections, and increased risk of autoimmune disease and malignancy. Secondary amyloidosis develops from chronic inflammatory conditions. The co-existence of CVID (especially in patients with bronchiectasis) and secondary amyloidosis has been reported rarely. We describe the first case of pulmonary hypertension secondary to pulmonary amyloidosis in a patient with CVID. Keywords Common variable immunodeficiency . amyloidosis . pulmonary amyloidosis . pulmonary hypertension
of CVID include mainly acute sino-pulmonary infections and chronic pulmonary diseases (bronchiectasis, obstructive and restrictive lung diseases, lymphoid interstitial pneumonitis, and rarely granulomatous lung disease) [2]. Secondary amyloidosis due to ongoing inflammation from recurrent infections and autoimmunity is an expected clinical presentation in patients with CVID, but such co-existence has been seen in only a few case reports. Pulmonary amyloidosis is a rare condition associated mostly with the light chain form (AL type), rather than secondary (AA type) amyloidosis [3]. Here, we present the first case of pulmonary amyloidosis in a CVID patient complicated by kidney and possibly adrenal gland (could not be demonstrated) involvement.
Patient Past medical history Introduction Common variable immunodeficiency (CVID) is a heterogeneous collection of disorders resulting mostly from antibody deficiency and recurrent infections. It is the most common symptomatic form of severe antibody deficiency affecting both children and adults [1]. The pulmonary complications S. Arslan : R. Ucar (*) : I. Reisli : A. Z. Calıskaner Meram Faculty of Medicine, Department of Clinical Immunology and Allergy, Necmettin Erbakan University, Konya 42090, Turkey e-mail: [email protected] D. M. Yavsan : E. Maden Meram Faculty of Medicine, Department of Pulmonology, Necmettin Erbakan University, Konya, Turkey H. Esen Meram Faculty of Medicine, Department of Pathology, Necmettin Erbakan University, Konya, Turkey
Our patient was referred to the pediatric immunology clinic (approximately 11 years ago at the age of 16 years) because of recurrent sino-pulmonary infections and chronic diarrhea for 6 years. He was the first-born child of consanguineous parents of Turkish descent with no family history of primary immunodeficiency (PID). His two brothers and one daughter were healthy, and his parents had no history of miscarriage. The patient’s serum immunoglobulin levels were decreased: IgG 3.52 g/L, IgA 0.248 g/L, IgM 0.191 g/L, and IgE 14.2 IU/mL. He was investigated for co-morbidities and complications of PID, and bronchiectasis was observed using pulmonary computerized tomography. The diagnosis of PID (most likely CVID) was established based on low serum IgG levels, consanguinity, a medical history of recurrent infection, sustained diarrhea, and absence of all other secondary causes of hypogammaglobulinemia. The patient was started on immunoglobulin replacement therapy (polyclonal immunoglobulin,
J Clin Immunol (2015) 35:344–347
345
400 mg/kg, every 3 weeks by IV) and prophylactic antibiotics (trimetoprim-sulfametoxazol, 800/160 mg, three times weekly) because of bronchiectasis. Unfortunately, his family was unconcerned about the disease, and the patient was noncompliant with treatment. The severity and complications of the disease increased over time. Current medical history The patient was followed up in our clinic (adult clinical immunology) at the age of 24 years. The diagnosis and complications of CVID were confirmed, and the treatment was continued (Ig replacement and prophylactic antibiotics). However, the non-compliance of the patient continued. At the second year of follow up, after a long period without treatment, he presented with abdominal ascites, pleural effusion, and pre-tibial edema upon physical examination at 26 years old. Based on spot urine analysis, proteinuria (without hematuria) was observed. The serum albumin level was 1.6 g/dL, and the protein loss based on a quantitative 24-h urine test was at nephrotic levels (11 g/day). Massive porteinuria, a history of bronchiectasis, and recurrent infections suggested that renal amyloidosis may have developed. We consulted nephrology, and a renal biopsy was performed. Based on histological examination, there was Congo red-positive amyloid deposition in the glomeruli, tubule, and interstitium. Positive expression with BCongo red^ was not achieved after staining with potassium permanganate that indicates secondary type of amyloidosis. The genetic test for Familial Mediterranean Fever was negative. The patient was treated with colchicum, losartan (angiotensin receptor-II blocker), essential amino acids, diuretics, and IVIG (1 g/kg) every 2 weeks. After 8 months, he was admitted with dyspnea, fever (38.5 °C), and pulmonary infiltration based on a chest X-ray, and meropenem (1 g, tid, IV) was administered. Dyspnea did not improve with the antibiotic therapy, and hypoxemia that could not be corrected with oxygen therapy developed. We performed echocardiography, and the ejection fraction was normal (%60), but the pulmonary artery pressure (PAP) was increased (65 mm Hg). Pulmonary parenchymal pathology was considered because of progressive dyspnea, pulmonary hypertension, and hypoxemia, and a transbronchial biopsy was performed using a bronchoscope after consulting a pulmonary specialist. Histological examination revealed amyloid depositions (Fig. 1). On the 35th day of hospitalization, his blood pressure (BP) was decreased (80/40 mm Hg) and tachycardia (108/min) had developed. He was then transferred to an intensive care unit. Positive inotropic (dopamine IV) was commenced, but his BP did not increase. This condition was suggestive of adrenal insufficiency, most probably secondary amyloid deposition. Thus, we performed an ACTH stimulation test. Serum cortisol levels were 8.53 μg/dL (30 min),
Fig. 1 Large image: Inflammatory cell infiltration inferior to bronchial epithelia (white arrow) and vascular structure (yellow arrow) (Hemotoxilen and Eosin, ×200). Small image: Positive expression with ‘Congo Red’ is seen on the wall vascular structure (yellow arrow) (×400)
9.5 μg/dL (60 min), and 11.9 μg/dL (120 min), and this result suggested probable diagnosis of adrenal insufficiency. In addtion, amyloid deposition in autonomic nerves and in vascular wall may contribute hypotension. Methylprednisolone (40 mg/day IV) was commenced and BP normalized. Unfortunately, despite the intensive care unit follow up, the patient’s condition had deteriorated, and infection control and stabilization of the patient could not be achieved. On the 75th day of admission, the patient died due to septic shock.
Discussion Amyloidosis is characterized by abnormal protein deposition in the β-sheet structures of the extracellular matrix of tissues, leading to progressive dysfunction of the involved organs [4]. Amyloid protein is stained using Congo red and exhibits apple-green birefringence under polarized microscopy. There are four types of amyloidosis: primary amyloidosis (also known as light chain amyloidosis), secondary, senile (transthyretin), and dialysis-associated β2 microglobulin amyloidosis. While AL type amyloidosis occurs with plasma cell dyscrasias, the AA type occurs together with chronic inflammatory conditions such as rheumatic disease (e.g., Familial Mediterranean Fever, rheumatoid arthritis, ankylosing spondilitis), chronic infections (e.g., tuberculosis, bronchiectasis, osteomyelitis), and some cancers that are observed in CVID patients. However, only a small number of CVID patients with secondary amyloidosis (renal, intestinal, and thyroid involvement) have been reported to date [4–7]. There are several explanations for this lower prevalence; clinicians do not evaluate the patients for amyloidosis since the diagnosis requires invasive procedures (generally rectal biopsy), and
346
symptoms of amyloidosis are non-specific and can easily be attributed to other causes. In addition, in some CVID patients, we expect a higher incidence of amyloidosis because of chronic and recurrent infections due to delayed CVID diagnosis and/or patient negligence. Amyloidosis is a very rare condition with an incidence of eight patients per million per year [8]. Pulmonary amyloidosis generally is observed together with systemic AL amyloidosis, and 88 % of patients with systemic amyloidosis show pulmonary involvement upon autopsy [9, 10]. Pulmonary amyloid deposition in secondary amyloidosis cases is a rare condition with a negative prognostic impact. Utz et al. reported that only two of 55 patients with pulmonary amyloidosis had secondary amyloidosis, showing a median survival of 16 months [9]. In an autopsy trial, only one of 113 patients with secondary amyloidosis was reported to have pulmonary amyloidosis [10]. Clinical manifestations of pulmonary amyloidosis include dyspnea, chest tightness, cough, expectoration, chest pain, weight loss, and hemoptysis [11]. The differential diagnosis of pulmonary amyloidosis includes metastatic tumor, congestive heart failure, miliary tuberculosis, sarcoidosis, silicosis, hypersensitivity pneumonitis, and interstitial lung disease [12]. In our CVID patient, there was renal and probably adrenal gland involvement of secondary amyloidosis. We performed echocardiography because of the progressive dyspnea and uncorrected hypoxemia with oxygen treatment. PAP was increased (65 mm Hg). Pulmonary hypertension and unrecoverable hypoxemia, despite oxygen and bronchodilator therapy, were suggestive of a pulmonary parenchymal pathology. Long-term bronchiectasis and left ventricular failure may have contributed to the increased PAP, but left ventricular function was preserved according to echocardiographic assessment. Therefore, we consulted a pulmonary specialist and decided to perform transbronchial biopsy to identify any treatable pulmonary parenchymal pathology for improvement of the patient’s condition. Finally, we determined that pulmonary amyloidosis was the underlying pathology. Nine cases of pulmonary hypertension (PHT) and amyloidosis have been reported. Only one was secondary amyloidosis due to Familial Mediterranean Fever. Their median survival was 73 days after diagnosis of pulmonary hypertension [13]. Similarly, our patient died 74 days after the PHT diagnosis. The development of PHT in patients with pulmonary amyloidosis is a very important prognostic factor. The prevalence of systemic amyloidosis in patients with CVID remains unclear, and few case reports exist. There is no consensus regarding when and how to evaluate CVID patients in terms of amyloidosis, especially for pulmonary involvement. Fatigue, dyspnea, edema, paresthesias, and weight loss are important symptoms of amyloidosis, even though they are non-specific. Twenty-four-hour urine examination
J Clin Immunol (2015) 35:344–347
for proteinuria is a crucial method to assess suspected renal amyloidosis. Radiological evaluation of the lungs for amyloid deposition, progressive dyspnea without obvious causes, and unrecoverable hypoxemia due to decreased diffusion capacity may be suggestive of pulmonary amyloidosis. In suspected patients, bronchoscopic biopsy with appropriate staining is the gold standard for diagnosis of pulmonary amyloidosis.
Conclusion Even though the number of reported cases is very low, amyloidosis is an important complication and may be more frequent than reported in patients with CVID. Health care professionals, especially clinical immunologists, should consider amyloidosis. Compliance with ethical standards Informed consent Written and verbal informed consent was taken from the parent of the patient.
References 1. Yong PF, Thaventhiran JE, Grimbacher B. BA rose is a rose is a rose,^ but CVID is Not CVID common variable immune deficiency (CVID), what do we know in 2011? Adv Immunol. 2011;111: 47–107. 2. Busse PJ, Farzan S, Cunningham-Rundles C. Pulmonary complications of common variable immunodeficiency. Ann Allergy Asthma Immunol. 2007;98:1–8. 3. Ozer Simsek Z, Oymak FS, Tutar N, Canoz O, Demir R. A rare cause of diffuse parenchymal lung disease together with granulomatous reaction: pulmonary amyloidosis. Case Rep Pulmonol. 2013;2013: 837190. 4. Borte S, Celiksoy MH, Menzel V, Ozkaya O, Ozen FZ, Hammarstrom L, et al. Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency. Clin Immunol. 2014;154:105–11. 5. Turkmen K, Anil M, Solak Y, Atalay H, Esen H, Tonbul HZ. A hepatitis C-positive patient with new onset of nephrotic syndrome and systemic amyloidosis secondary to common variable immunodeficiency. Ann Saudi Med. 2010;30:401–3. 6. Kadiroglu AK, Yildirim Y, Yilmaz Z, Kayabasi H, Avci Y, Yildirim MS, et al. A rare cause of secondary amyloidosis: common variable immunodeficiency disease. Case Rep Nephrol. 2012;2012:860208. 7. Celik AF, Altiparmak MR, Pamuk GE, Pamuk ON, Tabak F. Association of secondary amyloidosis with common variable immune deficiency and tuberculosis. Yonsei Med J. 2005;46:847–50. 8. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR. Amyloidosis. Best Pract Res Clin Haematol. 2005;18:709–27. 9. Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996;124: 407–13. 10. Smith RR, Hutchins GM, Moore GW, Humphrey RL. Type and distribution of pulmonary parenchymal and vascular amyloid. Correlation with cardiac amyloid. Am J Med. 1979;66:96–104.
J Clin Immunol (2015) 35:344–347 11. Chu H, Zhao L, Zhang Z, Gui T, Yi X, Sun X. Clinical characteristics of amyloidosis with isolated respiratory system involvement: a review of 13 cases. Ann Thorac Med. 2012;7:243–9. 12. Higo H, Fujiwara K, Watanabe H, Makimoto G, Kameyama N, Matsushita M, et al. Diffuse parenchymal pulmonary amyloidosis
347 showing an objective response to Bortezomib-based chemotherapy. Intern Med. 2014;53:1809–12. 13. Eder L, Zisman D, Wolf R, Bitterman H. Pulmonary hypertension and amyloidosis—an uncommon association: a case report and review of the literature. J Gen Intern Med. 2007;22:416–9.
BRIEF COMMUNICATION
Common Variable Immunodeficiency and Pulmonary Amyloidosis: A Case Report Sevket Arslan & Ramazan Ucar & Dudu Mehmet Yavsan & Hasan Esen & Emin Maden & Ismail Reisli & Ahmet Zafer Calıskaner
Received: 26 December 2014 / Accepted: 4 March 2015 / Published online: 14 March 2015 # Springer Science+Business Media New York 2015
Abstract Common variable immunodeficiency is the most common symptomatic primary immune deficiency characterized by hypogammaglobulinemia, recurrent infections, and increased risk of autoimmune disease and malignancy. Secondary amyloidosis develops from chronic inflammatory conditions. The co-existence of CVID (especially in patients with bronchiectasis) and secondary amyloidosis has been reported rarely. We describe the first case of pulmonary hypertension secondary to pulmonary amyloidosis in a patient with CVID. Keywords Common variable immunodeficiency . amyloidosis . pulmonary amyloidosis . pulmonary hypertension
of CVID include mainly acute sino-pulmonary infections and chronic pulmonary diseases (bronchiectasis, obstructive and restrictive lung diseases, lymphoid interstitial pneumonitis, and rarely granulomatous lung disease) [2]. Secondary amyloidosis due to ongoing inflammation from recurrent infections and autoimmunity is an expected clinical presentation in patients with CVID, but such co-existence has been seen in only a few case reports. Pulmonary amyloidosis is a rare condition associated mostly with the light chain form (AL type), rather than secondary (AA type) amyloidosis [3]. Here, we present the first case of pulmonary amyloidosis in a CVID patient complicated by kidney and possibly adrenal gland (could not be demonstrated) involvement.
Patient Past medical history Introduction Common variable immunodeficiency (CVID) is a heterogeneous collection of disorders resulting mostly from antibody deficiency and recurrent infections. It is the most common symptomatic form of severe antibody deficiency affecting both children and adults [1]. The pulmonary complications S. Arslan : R. Ucar (*) : I. Reisli : A. Z. Calıskaner Meram Faculty of Medicine, Department of Clinical Immunology and Allergy, Necmettin Erbakan University, Konya 42090, Turkey e-mail: [email protected] D. M. Yavsan : E. Maden Meram Faculty of Medicine, Department of Pulmonology, Necmettin Erbakan University, Konya, Turkey H. Esen Meram Faculty of Medicine, Department of Pathology, Necmettin Erbakan University, Konya, Turkey
Our patient was referred to the pediatric immunology clinic (approximately 11 years ago at the age of 16 years) because of recurrent sino-pulmonary infections and chronic diarrhea for 6 years. He was the first-born child of consanguineous parents of Turkish descent with no family history of primary immunodeficiency (PID). His two brothers and one daughter were healthy, and his parents had no history of miscarriage. The patient’s serum immunoglobulin levels were decreased: IgG 3.52 g/L, IgA 0.248 g/L, IgM 0.191 g/L, and IgE 14.2 IU/mL. He was investigated for co-morbidities and complications of PID, and bronchiectasis was observed using pulmonary computerized tomography. The diagnosis of PID (most likely CVID) was established based on low serum IgG levels, consanguinity, a medical history of recurrent infection, sustained diarrhea, and absence of all other secondary causes of hypogammaglobulinemia. The patient was started on immunoglobulin replacement therapy (polyclonal immunoglobulin,
J Clin Immunol (2015) 35:344–347
345
400 mg/kg, every 3 weeks by IV) and prophylactic antibiotics (trimetoprim-sulfametoxazol, 800/160 mg, three times weekly) because of bronchiectasis. Unfortunately, his family was unconcerned about the disease, and the patient was noncompliant with treatment. The severity and complications of the disease increased over time. Current medical history The patient was followed up in our clinic (adult clinical immunology) at the age of 24 years. The diagnosis and complications of CVID were confirmed, and the treatment was continued (Ig replacement and prophylactic antibiotics). However, the non-compliance of the patient continued. At the second year of follow up, after a long period without treatment, he presented with abdominal ascites, pleural effusion, and pre-tibial edema upon physical examination at 26 years old. Based on spot urine analysis, proteinuria (without hematuria) was observed. The serum albumin level was 1.6 g/dL, and the protein loss based on a quantitative 24-h urine test was at nephrotic levels (11 g/day). Massive porteinuria, a history of bronchiectasis, and recurrent infections suggested that renal amyloidosis may have developed. We consulted nephrology, and a renal biopsy was performed. Based on histological examination, there was Congo red-positive amyloid deposition in the glomeruli, tubule, and interstitium. Positive expression with BCongo red^ was not achieved after staining with potassium permanganate that indicates secondary type of amyloidosis. The genetic test for Familial Mediterranean Fever was negative. The patient was treated with colchicum, losartan (angiotensin receptor-II blocker), essential amino acids, diuretics, and IVIG (1 g/kg) every 2 weeks. After 8 months, he was admitted with dyspnea, fever (38.5 °C), and pulmonary infiltration based on a chest X-ray, and meropenem (1 g, tid, IV) was administered. Dyspnea did not improve with the antibiotic therapy, and hypoxemia that could not be corrected with oxygen therapy developed. We performed echocardiography, and the ejection fraction was normal (%60), but the pulmonary artery pressure (PAP) was increased (65 mm Hg). Pulmonary parenchymal pathology was considered because of progressive dyspnea, pulmonary hypertension, and hypoxemia, and a transbronchial biopsy was performed using a bronchoscope after consulting a pulmonary specialist. Histological examination revealed amyloid depositions (Fig. 1). On the 35th day of hospitalization, his blood pressure (BP) was decreased (80/40 mm Hg) and tachycardia (108/min) had developed. He was then transferred to an intensive care unit. Positive inotropic (dopamine IV) was commenced, but his BP did not increase. This condition was suggestive of adrenal insufficiency, most probably secondary amyloid deposition. Thus, we performed an ACTH stimulation test. Serum cortisol levels were 8.53 μg/dL (30 min),
Fig. 1 Large image: Inflammatory cell infiltration inferior to bronchial epithelia (white arrow) and vascular structure (yellow arrow) (Hemotoxilen and Eosin, ×200). Small image: Positive expression with ‘Congo Red’ is seen on the wall vascular structure (yellow arrow) (×400)
9.5 μg/dL (60 min), and 11.9 μg/dL (120 min), and this result suggested probable diagnosis of adrenal insufficiency. In addtion, amyloid deposition in autonomic nerves and in vascular wall may contribute hypotension. Methylprednisolone (40 mg/day IV) was commenced and BP normalized. Unfortunately, despite the intensive care unit follow up, the patient’s condition had deteriorated, and infection control and stabilization of the patient could not be achieved. On the 75th day of admission, the patient died due to septic shock.
Discussion Amyloidosis is characterized by abnormal protein deposition in the β-sheet structures of the extracellular matrix of tissues, leading to progressive dysfunction of the involved organs [4]. Amyloid protein is stained using Congo red and exhibits apple-green birefringence under polarized microscopy. There are four types of amyloidosis: primary amyloidosis (also known as light chain amyloidosis), secondary, senile (transthyretin), and dialysis-associated β2 microglobulin amyloidosis. While AL type amyloidosis occurs with plasma cell dyscrasias, the AA type occurs together with chronic inflammatory conditions such as rheumatic disease (e.g., Familial Mediterranean Fever, rheumatoid arthritis, ankylosing spondilitis), chronic infections (e.g., tuberculosis, bronchiectasis, osteomyelitis), and some cancers that are observed in CVID patients. However, only a small number of CVID patients with secondary amyloidosis (renal, intestinal, and thyroid involvement) have been reported to date [4–7]. There are several explanations for this lower prevalence; clinicians do not evaluate the patients for amyloidosis since the diagnosis requires invasive procedures (generally rectal biopsy), and
346
symptoms of amyloidosis are non-specific and can easily be attributed to other causes. In addition, in some CVID patients, we expect a higher incidence of amyloidosis because of chronic and recurrent infections due to delayed CVID diagnosis and/or patient negligence. Amyloidosis is a very rare condition with an incidence of eight patients per million per year [8]. Pulmonary amyloidosis generally is observed together with systemic AL amyloidosis, and 88 % of patients with systemic amyloidosis show pulmonary involvement upon autopsy [9, 10]. Pulmonary amyloid deposition in secondary amyloidosis cases is a rare condition with a negative prognostic impact. Utz et al. reported that only two of 55 patients with pulmonary amyloidosis had secondary amyloidosis, showing a median survival of 16 months [9]. In an autopsy trial, only one of 113 patients with secondary amyloidosis was reported to have pulmonary amyloidosis [10]. Clinical manifestations of pulmonary amyloidosis include dyspnea, chest tightness, cough, expectoration, chest pain, weight loss, and hemoptysis [11]. The differential diagnosis of pulmonary amyloidosis includes metastatic tumor, congestive heart failure, miliary tuberculosis, sarcoidosis, silicosis, hypersensitivity pneumonitis, and interstitial lung disease [12]. In our CVID patient, there was renal and probably adrenal gland involvement of secondary amyloidosis. We performed echocardiography because of the progressive dyspnea and uncorrected hypoxemia with oxygen treatment. PAP was increased (65 mm Hg). Pulmonary hypertension and unrecoverable hypoxemia, despite oxygen and bronchodilator therapy, were suggestive of a pulmonary parenchymal pathology. Long-term bronchiectasis and left ventricular failure may have contributed to the increased PAP, but left ventricular function was preserved according to echocardiographic assessment. Therefore, we consulted a pulmonary specialist and decided to perform transbronchial biopsy to identify any treatable pulmonary parenchymal pathology for improvement of the patient’s condition. Finally, we determined that pulmonary amyloidosis was the underlying pathology. Nine cases of pulmonary hypertension (PHT) and amyloidosis have been reported. Only one was secondary amyloidosis due to Familial Mediterranean Fever. Their median survival was 73 days after diagnosis of pulmonary hypertension [13]. Similarly, our patient died 74 days after the PHT diagnosis. The development of PHT in patients with pulmonary amyloidosis is a very important prognostic factor. The prevalence of systemic amyloidosis in patients with CVID remains unclear, and few case reports exist. There is no consensus regarding when and how to evaluate CVID patients in terms of amyloidosis, especially for pulmonary involvement. Fatigue, dyspnea, edema, paresthesias, and weight loss are important symptoms of amyloidosis, even though they are non-specific. Twenty-four-hour urine examination
J Clin Immunol (2015) 35:344–347
for proteinuria is a crucial method to assess suspected renal amyloidosis. Radiological evaluation of the lungs for amyloid deposition, progressive dyspnea without obvious causes, and unrecoverable hypoxemia due to decreased diffusion capacity may be suggestive of pulmonary amyloidosis. In suspected patients, bronchoscopic biopsy with appropriate staining is the gold standard for diagnosis of pulmonary amyloidosis.
Conclusion Even though the number of reported cases is very low, amyloidosis is an important complication and may be more frequent than reported in patients with CVID. Health care professionals, especially clinical immunologists, should consider amyloidosis. Compliance with ethical standards Informed consent Written and verbal informed consent was taken from the parent of the patient.
References 1. Yong PF, Thaventhiran JE, Grimbacher B. BA rose is a rose is a rose,^ but CVID is Not CVID common variable immune deficiency (CVID), what do we know in 2011? Adv Immunol. 2011;111: 47–107. 2. Busse PJ, Farzan S, Cunningham-Rundles C. Pulmonary complications of common variable immunodeficiency. Ann Allergy Asthma Immunol. 2007;98:1–8. 3. Ozer Simsek Z, Oymak FS, Tutar N, Canoz O, Demir R. A rare cause of diffuse parenchymal lung disease together with granulomatous reaction: pulmonary amyloidosis. Case Rep Pulmonol. 2013;2013: 837190. 4. Borte S, Celiksoy MH, Menzel V, Ozkaya O, Ozen FZ, Hammarstrom L, et al. Novel NLRP12 mutations associated with intestinal amyloidosis in a patient diagnosed with common variable immunodeficiency. Clin Immunol. 2014;154:105–11. 5. Turkmen K, Anil M, Solak Y, Atalay H, Esen H, Tonbul HZ. A hepatitis C-positive patient with new onset of nephrotic syndrome and systemic amyloidosis secondary to common variable immunodeficiency. Ann Saudi Med. 2010;30:401–3. 6. Kadiroglu AK, Yildirim Y, Yilmaz Z, Kayabasi H, Avci Y, Yildirim MS, et al. A rare cause of secondary amyloidosis: common variable immunodeficiency disease. Case Rep Nephrol. 2012;2012:860208. 7. Celik AF, Altiparmak MR, Pamuk GE, Pamuk ON, Tabak F. Association of secondary amyloidosis with common variable immune deficiency and tuberculosis. Yonsei Med J. 2005;46:847–50. 8. Gertz MA, Lacy MQ, Dispenzieri A, Hayman SR. Amyloidosis. Best Pract Res Clin Haematol. 2005;18:709–27. 9. Utz JP, Swensen SJ, Gertz MA. Pulmonary amyloidosis. The Mayo Clinic experience from 1980 to 1993. Ann Intern Med. 1996;124: 407–13. 10. Smith RR, Hutchins GM, Moore GW, Humphrey RL. Type and distribution of pulmonary parenchymal and vascular amyloid. Correlation with cardiac amyloid. Am J Med. 1979;66:96–104.
J Clin Immunol (2015) 35:344–347 11. Chu H, Zhao L, Zhang Z, Gui T, Yi X, Sun X. Clinical characteristics of amyloidosis with isolated respiratory system involvement: a review of 13 cases. Ann Thorac Med. 2012;7:243–9. 12. Higo H, Fujiwara K, Watanabe H, Makimoto G, Kameyama N, Matsushita M, et al. Diffuse parenchymal pulmonary amyloidosis
347 showing an objective response to Bortezomib-based chemotherapy. Intern Med. 2014;53:1809–12. 13. Eder L, Zisman D, Wolf R, Bitterman H. Pulmonary hypertension and amyloidosis—an uncommon association: a case report and review of the literature. J Gen Intern Med. 2007;22:416–9.
