My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?

Night sweats (NS) is a common patient complaint, affecting about a third of hospitalized patients on medical wards1.  Despite its long list of potential causes, direct relationship between the often- cited conditions and NS is usually unclear2, its cause may remain elusive In about a third to half of cases in the primary care setting, and its prognosis, at least in those >65 y of age, does not appear to be unfavorable 2,3.

Selected commonly and less frequently cited conditions associated with NS are listed (Table)2-9.  Although tuberculosis is one of the first conditions we think of when faced with a patient with NS, it should be emphasized that NS is not common in this disease (unless advanced) and is rare among hospitalized patients as a cause of their NS1,9.

In one of the larger study of adult patients seen in primary care setting, 23% reported pure NS and an additional 18% reported night and day sweats5; the prevalence of NS in both men and women was highest in 41-55 y age group. In multivariate analyses, factors associated with pure NS in women were hot flashes and panic attacks; in men, sleep disorders. 

Table. Selected causes of night sweats

Commonly cited Less frequently cited
Neoplastic/hematologic (eg, lymphoma, leukemia, myelofibrosis)

Infections (eg, HIV, tuberculosis, endocarditis)

Endocrine (eg, ovarian failure, hyperthyroidism, orchiectomy, carcinoid tumor, diabetes mellitus [nocturnal hypoglycemia], pheochromocytoma)

Rheumatologic (eg, giant cell arteritis)

Gastroesophageal reflux disease

B-12 deficiency

Pulmonary embolism

Drugs (eg, anti-depressants, SSRIs, donepezil [Aricept], tacatuzumab)

Sleep disturbances (eg, obstructive sleep apnea)

Panic attacks/anxiety disorder

Obesity

Hemachromatosis

Diabetes insipidus

References

  1. Lea MJ, Aber RC, Descriptive epidemiology of night sweats upon admission to a university hospital. South Med J 1985;78:1065-67.
  2. Mold JW, Holtzclaw BJ, McCarthy L. Night sweats: A systematic review of the literature. J Am Board Fam Med 2012; 25-878-893.
  3. Mold JW, Lawler F. The prognostic implications of night sweats in two cohorts of older patients. J Am Board Fam Med 2010;23:97-103.
  4. Mold JW, Holtzclaw BJ. Selective serotonin reuptake inhibitors and night sweats in a primary care population. Drugs-Real World Outcomes 2015;2:29-33.
  5. Mold JW, Mathew MK, Belgore S, et al. Prevalence of night sweats in primary care patients: An OKPRN and TAFP-Net collaborative study. J Fam Pract 2002; 31:452-56.
  6. Feher A, Muhsin SA, Maw AM. Night sweats as a prominent symptom of a patient presenting with pulmonary embolism. Case reports in Pulmonology 2015. http://dx.doi.org/10.1155/2015/841272
  7. Rehman HU. Vitamin B12 deficiency causing night sweats. Scottish Med J 2014;59:e8-11.
  8. Murday HK, Rusli FD, Blandy C, et al. Night sweats: it may be hemochromatosis. Climacteric 2016;19:406-8.
  9. Fred HL. Night sweats. Hosp Pract 1993 (Aug 15):88.
My middle age patient complains of night sweats for several months, but she has had no weight loss and does not appear ill. What could I be missing?

How should I interpret a positive result for serum cryoglobulins?

Cryoglobulins (CGs) are immunoglobulins that precipitate in the blood under cold conditions (<37◦ C) and redissolve upon warming1.  The term “cryoglobulinemia” is commonly used to describe patients with a systemic inflammatory syndrome that is often associated with small-to-medium vessel vasculitis due to cryoglobulin-containing immune complexes. Although some patients with cryoglobulinemia may be asymptomatic, most present with a range of diseases characterized by fatigue, arthralgia, skin rashes or necrosis, purpura, neuropathy, bowel wall ischemia and/or glomerulonephritis and kidney failure.

Wintrobe and Buell are credited for first describing cryglobulinemia in 1933 when assessing a patient who ultimately was found to have multiple myeloma2. Since then the spectrum of diseases associated with CG has expanded to also include seemingly disparate conditions such as hepatitis C, autoimmune disorders and monoclonal gammopathy of undetermined significance (MGUS).  A commonly cited classification scheme for CG is shown (Table)3.   It should be emphasized that some CGs may not fit neatly into this scheme.

In our patient, the positive CG serum test should be interpreted in the clinical context in which it was obtained while searching for risk factors as well as signs and symptoms that may be associated with cryoglobulinemia.

 

Table. Classification of cryoglobulinemia

Category Description Examples
Type I Isolated monoclonal immunoglobulin, either IgM or IgG (less commonly IgA or free immunoglobulin light chains Multiple myeloma, Waldenström’s macroglobulinemia, monoclonal gammopathy of undetermined significance (MGUS)
Type II Mixture of monoclonal IgM and polyclonal IgG Hepatitis C, HIV, other viral infections
Type III Polyclonal mixture IgM and IgG Autoimmune disorders, hepatitis C

References

  1. Takada S, Shimizu T, Hadano Y, et al. Cryoglobulinemia (review). Mol Med Rep 2012;6:3-8
  2. Wintrobe MM, Buell MV. Hyperproteinemia associated with multiple myeloma. Bull Johns Hopkins Hosp 52: 156-165, 1933
  3. Brouet JC, Clauvel JP, Danon F, et al. Biological and clinical significance of cryoglobulins. Am J Med 1974; 57:775-88.

 

Contributed by Kirstin Scott, Medical Student, Harvard Medical School

How should I interpret a positive result for serum cryoglobulins?

When should I consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis in my non-HIV patient?

The most significant risk factor for PCP prophylaxis is defect in cell-mediated immunity including high-dose glucocorticoid (HDGC, ≥20 mg of prednisone daily) treatment1.  A systematic review concluded that at a PCP rate of 6.2% in control groups, PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP/STX) is highly effective (85% risk reduction) in non-HIV patients with acute leukemia or solid organ/autologous bone marrow  transplantation (number needed to treat 19)2.

Other Indications for PCP prophylaxis include1:

  1. HDGC treatment for ≥1month plus another cause of immunocompromise.
  2. Combination of immunosuppressive drugs, such as tumor-necrosing factor- α inhibitors plus HDGC or other immunosuppression.
  3. Polymyositis/dermatomyositis with interstitial pulmonary fibrosis on glucocorticoids.
  4. Certain primary immunodeficiencies (eg idiopathic CD4-lymphopenia, hyper-IgM syndrome).
  5. Granulomatosis with polyangiitis (Wegener’s) on methotrexate and HDGC
  6. Rheumatologic diseases on HDGC and a second immunosuppressive drug
  7. T-cell depleting agents (eg, fludarabine)
  8. Severe malnutrition

TMP/STX may be given either as double-strength 3x/week or single-strength daily1,2.

 

References

  1. Anevlavis S, Kaltsas K, Bouros D. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV infected patients. PNEUMON 2012;25, October-December.
  2. Stern A, Green H, Paul M, Leibovici L. Prophylaxis for pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients (Review). Cochrane data of Systematic Reviews 2014, issue 10. DOI: 10.1002/14651858.CD005590.pub3. 
When should I consider Pneumocystis jirovecii pneumonia (PCP) prophylaxis in my non-HIV patient?