Property:Explanation
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A minor is any individual of less than 18 years of age. Generally, a minor's parents have the right to refuse medical care for their child. But in the case of an emergency involving a minor, patient care must not be compromised despite family refusal. In emergency life-or-death situations, the physician must perform whatever it takes to save the minor's life regardless of the parent's decisions. The physician must not waste time calling for help or inquiring about legal issues in such emergency situations. On the contrary, physicians are protected by law to provide urgent care for minors.<br/>
'''Educational Objective:''' In life-or-death situations, a minor's emergency care must not be withheld under any circumstance.<br/>
'''References:''' +
Patient confidentiality is very important, and physicians are not allowed to disclose any information about adult patients' medical records, their diseases, treatment plans, prognosis, or even their identities as patients to other individuals. Adults are all individuals who are of 18 years of age or older. When confronted with situations where family members inquire about a patient, physicians should politely refrain from giving information without the patient's consent. Alternatively, physicians may ask the family members to speak directly with the patient to allow the patient full discretion in what he/she discloses.<br/>
'''Educational Objective:''' A physician must not disclose any information about adult patients to anyone without the patient's consent.<br/>
'''References:''' First Aid 2014 page 59 +
The technique described in the experiment appropriately reflects the variation in fiber composition. Myoglobin concentration varies significantly based on type I vs. type II muscle fibers. Type I muscle fibers contain high mitochondrial and high myoglobin content. Accordingly, they are referred to as "red" fibers (due to increased myoglobin concentrations). They are slow-twitch muscles active in sustained contractions and undergo oxidative phosphorylation. They are generally present in structural muscles. In contrast, type II muscle fibers are fast-twitch fibers that contain fewer mitochondrial content and fewer concentrations of myoglobin. They are referred to as "white" fibers. They are fast-twitching fibers and undergo anaerobic glycolysis. They are hypertrophied during weight-training and exercise. Muscle fibers from different muscles within the body are not exclusively composed of just 1 type of muscle fibers. Muscles are generally composed of both muscle fiber types, but the percentage of each fiber type varies according to the utility of the muscle. The soleus and the intermediate vastus muscles are type I predominant muscle. On the other hand, biceps brachii, psoas, vastus lateralis, triceps, and vastus lateralis (lateral vastus) muscles are all type II predominant muscles.<br/>
'''Educational Objective:''' Type I muscle fibers have less myoglobin concentrations than type II muscle fibers. The soleus and the intermediate vastus muscles are type I predominant muscle. On the other hand, biceps brachii, psoas, vastus lateralis, triceps, and lateral vastus muscles are all type II predominant muscles.<br/>
'''References:''' Bekedam MA, van Beek-Harmsen BJ, van Mechelen W, et al. Myoglobin concentration in skeletal muscle fibers of chronic heart failure patients. J Appl Physiol (1985). 2009;107(4):1138–1143.<br>
First Aid 2014 page 417 +
Both processes (intramembranous and the endochondral ossification) are required for osteogenesis. Intramembranous ossification does not involve cartilage, and bone is formed directly by the formation of osteoblasts from neural crest-derived mesenchymal cells. These cells secrete collagen-proteoglycan matrix that binds to calcium salts to ultimately calcify the osteoid (pre-bone). As osteoblasts aid in the calcification process, they are trapped within the matrix. Trapped cells are differentiated into osteocytes (mature bone cells). Intramembranous ossification requires the activation of transcription factors, such as CBFA1. On the other hand, endochondral ossification requires cartilage from mesenchyme cells that are ultimately replaced by bone. Endochondral ossification leads to formation of cartilage by chondrocytes that secrete the extracellular matrix. The cartilage forms a model that is eventually replaced by bone, starting at the center and then in the outward direction towards the edges. Osteoblasts form at the edge of the cartilage model and slowly replace cartilage by bone. Involvement of Pax1 and Scleraxis, 2 transcription factors, is required for formation of endochondral ossification. Osteoclasts, derived from macrophage stem cells, are linked to the matrix and pump hydrogen ions onto the matrix to acidify and dissolve it. Osteoprotegerin and its ligand are required for the conversion of macrophage stem cells into osteoclasts. Osteoclasts are under strict hormonal regulation at all times under physiologic conditions.<br/>
'''Educational Objective:''' Osteoblasts are derived from mesenchymal cells that originate from the neural crest, while osteoclasts are derived from macrophage stem cells.<br/>
'''References:''' Gilbert SF. Osteogenesis: The development of bone. in Developmental Biology. 6th ed. Sinauer Associates, Sunderland (MA): 2000.<br>
First Aid 2014 page 419 +
Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic, autoimmune neuromuscular disorder that is present in approximately half of patients with SCLC. LEMS is characterized by the formation of auto-antibodies against voltage-gated calcium (Ca++) channels (VGCC) on the pre-synaptic nerve terminal. Similar to myasthenia gravis (MG), LEMS is also a neuromuscular junction disease. However, LEMS is characterized by incremental improvement of the junction following repetitive stimulation, while MG is characterized by junctional fatigue (loss of action potential generation) following repetitive stimulation. LEMS typically manifests with proximal muscle weakness, which often starts in the lower extremities and progresses to involve the upper extremities. Similar to MG, ocular involvement is also common with LEMS. On physical examination, muscle weakness and tendinous areflexia are classic findings.<br/>
'''Educational Objective:''' Lambert-Eaton myasthenic syndrome (LEMS) is characterized by formation of auto-antibodies that target voltage-gated calcium (Ca++) channels (VGCC) in the pre-synaptic terminal of the neuromuscular junction.<br/>
'''References:''' Titulaer MJ, Lang B, Verschuuren J. Lambert-Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies. Lancet Neurol. 2011; 10:1098-107.<br>
First Aid 2015 page 435 +
Bisphosphonates are pyrophosphate analogues that bind to hydroxyapatite in the bone, thereby inhibiting osteoclast activity. Bisphosphonates are indicated for the treatment of osteoporosis, whereby inhibition of osteoclast-driven bone breakdown results in increased bone strength. Bisphosphonates are also indicated in Paget's disease to inhibit the abnormal cycling of osteoblastic and osteoclastic activity. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug event that rarely occurs with bisphosphonate use. The main risk factor for BRONJ is a history of dental procedures and/or poor dental hygiene. Patients who develop BRONJ often report a recent history of either dental extractions, tooth infection, or surgery of the maxillofacial region. Other secondary factors that also seem to be associated with BRONJ are corticosteroid therapy, radiotherapy, diabetes mellitus, and peripheral vascular disease.<br/>
'''Educational Objective:''' Development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is associated with a personal history of dental extractions, tooth infections, and surgery of the maxillofacial region.<br/>
'''References:''' Maerevoet M, Martin C, Duck L. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med. 2005;353(1):99-102.<br>
First Aid 2015 page 445 +
The patient is presenting with acetaminophen (paracetamol) toxicity. When patients with acetaminophen toxicity present late, it is not necessary to wait for the the serum concentration of acetaminophen, and administration of N-acetylcysteine prior to the return of serum concentration of acetaminophen is necessary. Symptoms of acetaminophen overdose are generally non-specific, and typical manifestations include abdominal pain and nausea. N-acetylcysteine is an antioxidant that regenerates glutathione and reduces the generation of toxic reactive oxygen species (ROS). It is used to reduce the effect of acetaminophen (paracetamol) toxicity. In addition, N-acetylcysteine is a mucolytic agent that is usually used to manage mucus plugging in patients with cystic fibrosis and chronic obstructive pulmonary disease (COPD).<br/>
'''Educational Objective:''' N-acetylcysteine is an antioxidant and mucolytic agent that is frequently used to manage mucus plugging in patients with cystic fibrosis and COPD.<br/>
'''References:''' Sadowska AM, Verbraecken J, Darquennes K, et al. Role of N-acetylcysteine in the management of COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(4):425-34.<br>
First Aid 2014 page 88, 252 +
The patient in this scenario is presenting with contact dermatitis following exposure to poison ivy, a common irritant. Poison ivy triggers Toxicodendron dermatitis (named after plant genus) due to the presence of urushiol, a clear liquid compound produced by the plant. Patients have varied reactions to poison ivy, with 25% of patients having no reaction, and 25% having a very severe eruption. The rash usually appears within 24 hours and resolves within 2 weeks. It may sometimes require topical steroids. Contact dermatitis is a type IV or delayed hypersensitivity reaction. The disease mechanism closely resembles that of Crohn's disease that is also considered a type IV hypersensitivity disorder. In a type IV reaction, CD8+ cytotoxic T cells recognize the antigen in a complex with class II MHC complex on antigen presenting cells. Activated CD8+ T cells then destroy target cells on contact. In Crohn's disease, delayed hypersensitivity reactions are suggested by the characteristic inflammatory granulomas along the GI tract. Treatment in patients with severe disease consists of TNF-alpha antagonists to attenuate the autoimmune reaction. Other diseases that are also classified as type IV hypersensitivity disorders include: multiple sclerosis, Guillain-Barre syndrome, graft-vs-host disease, and PPD testing for ''Mycobacterium tuberculosis''.<br/>
'''Educational Objective:''' Contact dermatitis and Crohn's disease are both caused by type IV hypersensitivity reactions.<br/>
'''References:''' First Aid 2014 page 208-209 +
''BRCA1'' and ''BRCA2'' are tumor suppressor genes whose mutation is associated with development of breast and ovarian cancers. Breast tissue normally expresses BRCA1 to protect dividing cells from DNA damage. During replication, if one strand of DNA breaks, a repair is easy, and the opposing strand can be used as template. If both strands of DNA are broken (double strand break), a seamless repair is much more difficult as the intervening sequence can be ambiguous. There are two methods of resolving a double strand break: 1. Non-homologous end joining (NHEJ) and 2. Homologous recombination. NHEJ is an error-prone method in which random sequence is inserted and ligated to bridge the break. Conversely, homologous recombination uses homologous sequence from a sister chromatid as template to facilitate perfect repair. BRCA1 is a key coordinator of homologous recombination based pair.<br>
BRCA1 binds to other proteins to form a complex that repairs DNA double strand break repairs by homologous recombination. Germline mutation of ''BRCA1'' predisposes individuals to the development of both breast and ovarian cancers. BRCA1 protein does not act as a tumor suppressor in the traditional sense that a protein like Retinoblastoma (Rb) protein does. Biallelic loss of BRCA1 itself is not thought to confer a growth advantage to cells. Instead, BRCA1 loss is a mechanism that allows for an increased probability of developing other oncogenic mutations. In this sense, ''BRCA1'' is more similar to a "caretaker" gene whose protein product brakes on cellular growth control. From a molecular perspective, Hereditary Breast and Ovarian Cancer (HBOC) syndrome is very similar to Hereditary Non-Polyposis Colorectal Cancer (HNPCC), which is caused by mutation in "caretaker" genes involved in DNA mismatch repair (''MSH2'' and ''MLH1'').<br>
A woman with a germline mutation in ''BRCA1'' has an 85% lifetime risk of developing breast cancer without intervention. The coding sequence of ''BRCA1'' is very long, and both inherited and sporadic mutations in it are common. ''BRCA2'' is also involved in DNA double strand break repair, and mutation in ''BRCA2'' causes a similarly increased risk of breast and ovarian cancers.<br/>
'''Educational Objective:''' ''BRCA'' tumor suppressor genes encode DNA double strand break repair proteins.<br/>
'''References:''' John EM, Miron A, Gong G, et al. Prevalence of pathogenic BRCA1 mutation carriers in 5 US racial/ethnic groups. JAMA. 2007;298(24):2869-76.<br>
First Aid 2014 page 232, 582, 585
Following a myocardial infarction, the heart undergoes gross and microscopic changes that are collectively referred to as the evolutionary process of MI:<br>
*0 to 4 hours post-MI: Very early following MI, the heart undergoes no gross or microscopic changes.<br>
*4 to 12 hours post-MI: The infarcted area starts to demonstrate dark mottling. During that period also, there is edema, coagulative necrosis, and hemorrhage. Wavy fibers are observed microscopically.<br>
*12 hours post-MI: Neutrophilic infiltration begins and contraction bands appear, signaling reperfusion injury. Necrotic changes are also observed during that time because cells release their necrotic material.<br>
*1 day post-MI: The infarcted area becomes hyperemic, and coagulative necrosis becomes more extensive with more inflammatory changes and neutrophilic migration. These changes persist for 3 days.<br>
*3 to 15 days post-MI: The border of the infarcted area becomes hyperemic and shows a soft yellowish infarcted region on gross pathology, and macrophage infiltration followed by granulation tissue is evident on light microscopy.<br>
*2 weeks post-MI: The infarcted area turns grayish and a contracted scar is formed. These changes persist for several months post-MI.<br/>
'''Educational Objective:''' At 3 to 15 days post-MI, light microscopy of the heart typically shows infiltration of macrophages and formation of granulation tissue.<br/>
'''References:''' +
The spleen is often ruptured following blunt trauma. The patient in this vignette is diagnosed with a traumatic splenic rupture and requires splenectomy to prevent fatal hemorrhage. Post-splenectomy, several physiologic changes may appear, all of which reflect the role of the spleen in handling and destroying defected red blood cells. Post-splenectomy, three classical changes appear: First, target cells (codocytes) and Howell-Jolly bodies may be observed on peripheral smear. Howell-Jolly bodies are basophilic nuclear remnants in red blood cells that are normally filtered by the spleen. Also, thrombocytosis is evident due to the loss of the spleen that normally eliminates platelets from the circulation. None of these findings is specific for post-splenectomy, and they are usually present in other conditions.<br/>
'''Educational Objective:''' Post-splenectomy, three classical changes appear: First, target cells (codocytes) and Howell-Jolly bodies may be observed on peripheral smear. Howell-Jolly bodies are basophilic nuclear remnants in red blood cells that are normally filtered by the spleen. Also, thrombocytosis is evident due to the loss of the spleen that normally eliminates platelets from the circulation.<br/>
'''References:''' +
<img src="http://static.wikidoc.org/7/73/Wjg_cachexia_illustration_12_30_14a.svg" width="700">
This patient presents displays signs and symptoms consistent with cachexia, a syndrome that is characterized by the presence of anorexia, fat loss, skeletal muscle wasting, severe asthenia, and fatigue. An unintentional loss of greater than 10% loss of body weight over a 12 month period that is associated with an underlying disease constitutes the technical definition of cachexia. Affected patients have dyspnea and severe weakness on minimal exertion or even at rest. Cachexia typically arises in the setting of cancer and other chronic inflammatory conditions such as AIDs, tuberculosis and COPD. The weight loss in cachectic patients is caused by both a decrease in appetite and a hypermetabolic state caused by higher resting energy expenditure. The precise reasons that cancers evolve to consistently induce cachexia are unknown. One hypothesis is that cancers induce cachexia to generate more bioavailable nutrients (glucose and amino acids) to sustain rapid tumor growth. Another hypothesis is that cancers maintain a complex relationship with stromal and immune cells in which inflammatory cytokines play an essential role. In this model, a systemic side-effect of high levels of these cytokines in the bloodstream is cachexia.
There is no scientific consensus on the specific cytokines responsible for inducing cachexia, but one of the prevailing candidates is TNF-alpha. TNF-alpha is sufficient to inhibit myocyte differentiation and induce myocyte atrophy in-vitro. Other mediators such as IL-6 and IFN-gamma may collaborate with TNF-alpha to promote cachexia. The only anti-cachexia drugs to date that have demonstrated benefit in phase III clinical trials are ghrelin analogues.
Note: While TNF-alpha is firmly entrenched in the USMLE canon as the mediator of cachexia, evidence in favor of TNF-alpha has weakened over time. There is no strong evidence that levels of TNF-alpha are increased in the circulation of cancer patients with weight loss. Trials of anti-TNF-alpha antibodies (infliximab) in cancer patients have also failed to show any clinical benefit. On the other hand, evidence in favor of IL-6 as a cachexia mediator is mounting. Circulating levels of IL-6 correlate with weight loss and reduced survival in cancer patients. Still, for the purposes of USMLE Step 1, remember that cachexia is caused by TNF-alpha.<br/>
'''Educational Objective:''' TNF-alpha (cachectin) is the main mediator of cachexia.<br/>
'''References:''' Gordon JN, Green SR, Goggin PM. Cancer cachexia. Q J Med. 2005; 98:779-788.<br>
Fearon, Kenneth CH, David J. Glass, and Denis C. Guttridge. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell metabolism 16.2 (2012): 153-166. <br>
Oliff, Allen, et al. Tumors secreting human TNF/cachectin induce cachexia in mice. Cell 50.4 (1987): 555-563. <br>
First Aid 2014 page 231
Plummer-Vinson syndrome (also known as Paterson-Kelly syndrome) is a rare disorder characterized by a triad of: dysphagia due to esophageal webs, glossitis (inflammation of the tongue), and iron deficiency anemia (IDA). Patients are classically middle-aged women, but age range is very wide as the disease has been described in children and elderly patients. Patients typically present with dysphagia to solids (not associated with odynophagia) that progresses over several years. Other signs and symptoms are due to associated conditions, such as skin pallor, fatigue, and tachycardia due to iron deficiency anemia. Additional findings on physical examination may include angular cheilitis (inflammation of labial commissures), koilonychia (nail spooning), palpable spleen, and/or palpable thyroid. The real etiology of Plummer-Vinson syndrome has not yet been identified, but several environmental and genetic predispositions have been described, including malnutrition and autoimmune diseases. The syndrome can be treated by iron replacement and mechanical dilation of the esophageal webs. Most importantly, Plummer-Vinson syndrome is associated with squamous cell carcinoma of the pharynx and the esophagus. Accordingly, patients diagnosed with this syndrome require close follow-up.<br/>
'''Educational Objective:''' Plummer-Vinson syndrome is a triad of glossitis, dysphagia due to esophageal webs, and iron deficiency anemia.<br/>
'''References:''' Novacek, G. Plummer-Vinson syndrome. Orphanet J Rare Dis. 2006; 1:36. +
Scleroderma defines a systemic disease that is characterized by thickening and fibrosis of the skin and internal organs to varying extents depending on the subtype. Two major forms of scleroderma exist: Limited scleroderma (CREST Syndrome) and diffuse scleroderma. CREST syndrome defines a milder form referring to a clinical pentad of '''C'''alcinosis, '''R'''aynaud's phenomenon, '''E'''sophageal dysfunction, '''S'''clerodactyly, and '''T'''elangiectasia, hence the term. The diffuse form is usually more rapidly progressive, involving large areas of skin and several internal organs. The prognosis of CREST syndrome is usually better than the diffuse form although both can be complicated by pulmonary hypertension. The etiology for both forms is unknown. Patients with CREST syndrome usually have anti-centromere antibodies while patients with diffuse scleroderma have anti-topoisomerase antibodies (anti-scl70). Treatment is mostly symptomatic.<br/>
'''Educational Objective:''' CREST syndrome is the limited form of scleroderma presenting with calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia. Patients are usually is positive for anti-centromere antibody.<br/>
'''References:''' UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review, BMC Dermatology 2004, 4:11. doi:10.1186/1471-5945-4-11 '''(Image)'''<br>
Gabrielli A, Avvedimento EV, Krieg T. Scleroderma. N Engl J Med. 2009;360(19):1989-2003. +
Sarcoidosis is a systemic disease characterized by the development and accumulation of multiple systemic granulomas. Sarcoidosis may involve virtually any organ but is classically most common in the lungs, liver, eyes, and skin. Symptoms of fatigue, night sweats, and weight loss are common at presentation. Löfgren's syndrome, a possible presentation of sarcoidosis consists of arthritis, erythema nodosum, and bilateral hilar adenopathy, and can be seen in up to 35% of patients. Although all racial and ethnic groups can have sarcoidosis, African Americans are 3 times more likely than Caucasians to develop the disease. Diagnosis is usually with a combination of clinical and radiologic findings supported by histopathological evidence of noncaseating epithelioid-cell granulomas with absence of any causative organisms or particles. Granulomas classicaly produce angiotensin-converting enzyme (ACE) with 60% of patients having elevated serum levels (not-diagnostic). Treatment is usually with corticosteroids although therapy is not indicated for everyone. Two thirds of patients recover completely within 10 years of diagnosis.<br/>
'''Educational Objective:''' Sarcoidosis is characterized by the development of multiple noncaseating epithelioid-cell granulomas.<br/>
'''References:''' Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007;357(21):2153-65. +
Lyme disease is a systemic animal-borne illness caused by the spirochete Borrelia burgdorferi transmitted by the Ixodes tick. The disease typically affects the skin, nervous system, musculoskeletal system and heart. The disease is mostly seen in the northeastern United States. The states with the highest incidence of lyme disease include Massachusetts, Pennsylvania, and New York. Classically the disease has 3 phases. The initial phase involves a typical rash known as erythema migrans that expands forming a bull's eye pattern with central clearing. The first stage occurs between 2-20 days after the initial tick bite and inoculation. The second stage is characterized by neurologic manifestations including meningitis, AV nodal block, and Bell's palsy usually occurring several weeks after the inital bite. The final phase, occurring several months to years after the inital exposure, is characterized by chronic monoarthritis and migratory polyarthritis with associated cutaneous manifestations. Treatment is usually with doxycyline or ceftriaxone.<br/>
'''Educational Objective:''' Several months after the initial inoculation of Borrelia burgdorferi, the most common clinical manifestation of untreated Lyme disease is chronic monoarthritis and migratory polyarthritis.<br/>
'''References:''' Biesiada G, Czepiel J, Leśniak MR, Garlicki A, Mach T. Lyme disease: review. Arch Med Sci. 2012;8(6):978-82. +
Lyme disease is a systemic animal-borne illness caused by the spirochete ''Borrelia burgdorferi'' transmitted by the Ixodes tick. The disease typically affects the skin, nervous system, musculoskeletal system and heart. The disease is mostly seen in the northeastern United States. In the initial phase of lyme disease, a characteristic rash known as erythema migrans evolves that expands forming a bull's eye pattern with central clearing. This usually occurs between 2-20 days after the initial tick bite and inoculation. The rash is not an inflammatory or an allergic reaction; it is the result of direct spirochetal infection of the skin and pathology examination reveals inflammation with spirochetes on silver stain. Treatment of lyme disease is with doxycyline or ceftriaxone.<br/>
'''Educational Objective:''' Erythema migrans is charactersitic of early stage lyme disease and is secondary to active spirochetal infection of the skin.<br/>
'''References:''' Biesiada G, Czepiel J, Leśniak MR, Garlicki A, Mach T. Lyme disease: review. Arch Med Sci. 2012;8(6):978-82. +
Psoriasis is an inflammatory skin disorder characterized by silvery white scales usually seen on the scalp, knees, and elbows. It is a T-lymphocyte associated auto-immune disease. Prevalence is estimated at 2% of the general population. Nail involvement and psoriatic arthritis can be seen in up to 25% of patients. Classically the plaques exhibit punctate bleeding when the scale is peeled off. This is known as the Auspitz sign. Features on pathological examination of a psoriatic lesion include keratinocyte hyperproliferation and hyperkeratosis, as well as leukocytic infiltration and angiogenesis. The stratum spinosum is usually thickened while the stratum granulosum becomes thinner. Neutrophils migrate to the epidermis then form Munro microabscesses which are characteristic of psoriasis.<br/>
'''Educational Objective:''' Psoriasis is an inflammatory skin disorder characterized on pathology by hyperkeratosis, angiogenesis, thickening of the stratum spinosum and munro microabscesses.<br/>
'''References:''' Schön MP, Boehncke WH. Psoriasis. N Engl J Med. 2005;352(18):1899-912. +
Cold agglutinin disease is a form of auto-immune hemolytic anemia caused by auto-antibodies to red blood cells that act at cold temperatures. It may either be a primary disease due to monoclonal antibodies, or secondary due to lymphoma, leukemia, EBV, CMV, HCV, ''Mycoplasma pneumoniae'' and several other infectious agents. The most common presenting symptom regardless of the underlying etiology is acrocyanosis (~40%). Acrocyanosis is defined as bluish-purplish discoloration of the distal fingertips and toes with cold exposure. Acrocyanosis may be associated with pain particularly in cold agglutinin disease. Other symptoms are specific to the underlying etiologies. Cold agglutinin disease presents more commonly in the winter months given its pathophysiology. Lab work-up may reveal anemia, reticulocytosis, elevated LDH and bilirubin, with decrease in haptoglobin. Cold agglutinin titers can also be tested. Titers can be so elevated that RBCs agglutinate even in anticoagulated blood samples at lower room temperatures.<br/>
'''Educational Objective:''' Cold agglutinin disease is an autoimmune hemolytic anemia with cold-reactive antibodies to RBCs. It can occur in patients with M. pneumoniae infection.<br/>
'''References:''' Swiecicki PL, Hegerova LT, Gertz MA. Cold agglutinin disease. Blood. 2013;122(7):1114-21. +
Hairy cell leukemia is a slowly progressive hematologic malignancy classically seen in older males. Patients usually present with anemia, thrombocytopenia and neutropenia despite normal or elevated white cell count. On physical exam, splenomegaly is common with easy bruising secondary to low platelets. Diagnosis is usually made by peripheral blood as well as bone marrow smear showing characteristic hairy cells (white blood cells with irregular, hair-like margins). The origin of hairy cells is B-lymphocytes although they may exhibit features of monocytes. The diagnosis can be confirmed by staining with tartrate-resistant acid phosphatase (TRAP). TRAP is a glycosylated enzyme expressed normally in other tissues (osteoclasts) but is markedly increased in "hairy cells". Patients are usually at very high risk of infection given their immune status.<br/>
'''Educational Objective:''' Hairy cell leukemia presents with cytopenia and splenomegaly with peripheral and bone marrow smear showing hairy cells. Tartrate-resistant acid phosphatase (TRAP) positivity may be used to confirm the diagnosis.<br/>
'''References:''' Zinzani PL, Pellegrini C, Stefoni V, et al. Hairy cell leukemia: evaluation of the long-term outcome in 121 patients. Cancer. 2010;116(20):4788-92. +