Which immunosuppression caused by long-term usage of these antibiotics in untreated celiac disease?

Which immunosuppression caused by long-term usage of these antibiotics in untreated celiac disease?

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These antibiotics include

  1. amoxicillin + acidum clavulanicum (beta-lactam, inhibit cell wall synthesis, broad specturm, 3rd gen aminopenicillin) / last part preventing the resistance
  2. ceftriaxone (3rd gen cephalosporine, inhibit cell wall synthesis, broad spectrum)
  3. clarithromycin (macrolide, inhibit protein synthesis by binding to ribosomal subunit S50)

used regularly for cyclic middle ear infections for years during the childhood - ages 2-10 for a patient with untreated celiac disease.

I am thinking what kind of immunosuppression can this lead to. I think it mostly conquered by suppression of adaptive immune system. Little lowered innate immunity lowered too.

I am especially interested in the antigen-presenting cells (mostly dendritic cells) and their function in an immunosuppressed patients of the antibiotics.

There may be other factors which I have not mentioned related to this kind of immunosuppression. Feel, free to propose.

How can dendritic cells work in an immunosuppressed patients?

You can assume any combination of cases for the three antibiotics: 8 possible cases. For instance,

  • (1) and (2) high antibiotic resistance, and only susceptible to (3)
  • High antibiotic resistance to (1)-(3)

Possible cases which reminds

  • this immunosuppression can remind this one: immune reconstitution syndrome like in HIV but milder

One possibility is that these antibiotics could disrupt your normal gut bacteria. Given that your gut has the surface area of a tennis court and is typically coated with symbiotic microbes, antimicrobial therapies could dramatically change the population dynamics of your gut ecosystem. One might imagine that the immune system of the gut is in homeostasis with these gut microbes, and if they all die off all at once because you're taking some sort of 'cillin, your immune system might suffer for lack of stimulation. Fewer immune cytokines released by your intestinal immune cells into your blood => systemic reduction in immune function.

Other possibilities could include: the drug just randomly fits into a bad spot on some important immune protein; the drug targets bacterial-related genes in the mitochondrial genome and disrupts the metabolism of the immune cells; the drug disrupts your ability to absorb nutrients required for immune function… the list of potential mechanisms is undoubtedly long.



The genera Bacteroides, Porphyromonas, Prevotella, and Fusobacterium account for the majority of infections caused by anaerobic gram-negative rods. Bilophila and Sutterella also cause human infections, although they are less frequently encountered in clinical practice. These obligately anaerobic gram-negative bacteria colonize the oropharynx, gastrointestinal tract, and urogenital tract of humans. Several species from some of these genera are useful symbiotic bacteria, facilitating host metabolism and favorably shaping immune responses. However, many of these microbes act opportunistically, causing infections when they gain access to otherwise sterile tissues. The gram-negative anaerobic rods have a predilection for abscess formation, with the most common sites being the oropharynx, abdominal cavity, lungs, and female genital tract. These bacterial species also present clinical challenges because they are often resistant to commonly used antibiotics. Recently, a few species from the Fusobacterium, Bilophila, and Sutterella genera have been associated with either inflammatory bowel disease or colon cancer, although causative roles have yet to be robustly established.


The skin serves as a protective barrier preventing normal skin flora and other microbial pathogens from reaching the subcutaneous tissue and lymphatic system. When a break in the skin occurs, it allows for normal skin flora and other bacteria to enter into the dermis and subcutaneous tissue. The introduction of these bacteria below the skin surface can lead to an acute superficial infection affecting the deep dermis and subcutaneous tissue, causing cellulitis. Cellulitis most commonly results from infection with group Aꂾta-hemolytic streptococcus (i.e., Streptococcus pyogenes).[3]

Risk factors for cellulitis include any culprit that could cause a breakdown in the skin barrier such as skin injuries, surgical incisions, intravenous site punctures, fissures between toes, insect bites, animal bites,ਊnd other skin infections.[4] Patients with comorbidities such as diabetes mellitus, venous insufficiency, peripheral arterial disease, and lymphedema are at higher risk ofꃞveloping cellulitis.[5]

Conclusions: antibiotics or probiotics as AD therapies?

As described above, alteration of the gut microbiota can induce changes in brain activity, which raises the possibility of therapeutic manipulation of the microbiome in AD and other neurological disorders (Fig. 1). The possibility of a therapeutic, or preventive, intervention using antibiotics in AD is intriguing because of the cost benefits of such treatments, which could be relatively inexpensive and can be combined with specific dietary regimen with probiotics to act synergistically. This field of research is currently undergoing great development, but therapeutic applications are still far away. Whether a therapeutic manipulation of gut microbiota in AD could be achieved using antibiotics or probiotics is still not known. The action of antibiotics in AD could be wide and even opposite, depending on the type of antibiotic (Table 1) and on the specific role of the microbiome in AD pathogenesis.

Schematic representation of the role of microbiota-gut-brain axis in Alzheimer’s disease. Good bacteria probiotics are capable to stabilize digestive pH, reduce inflammation, and increase neuroprotective molecules, such as brain-derived neurotrophic factor (BDNF). These effects lead to improved cognition and reduced Aβ plaque formation in AD animal models. In contrast, impaired microbiota dysbiosis can induce neuroinflammation and reduce the expression of BDNF and NMDA receptor, leading to cognitive impairment, mood disorders, and higher levels of Aβ42. Antibiotics, by affecting gut microbiota composition, interact with this circuit and produce different effects, depending on their microbiome target

As emerged from the studies mentioned, the use of antibiotics against gut microbiota specifically related to AD may be useful. The elimination of chronic infections caused by H. pylori or HSV1 virus can bring benefits to disease prevention, but also positive effects on cognitive functions. Nonetheless, clinical trials with antibiotics on patients already suffering from AD have led to conflicting results. Among the main problems, we must consider the multifactorial nature of the disease, which can be associated to an inflammatory state, but not exclusively. The presence of H. pylori infection, for example, may influence the outcome of a clinical trial, as its elimination may lead to cognitive improvements in affected patients, but it may prove ineffective in unaffected patients. Furthermore, there is always a real risk of causing dysbiosis in an attempt to reduce a state of neuroinflammation. Many antibiotics have a broad and not selective action on certain pathogens. In addition, other factors can affect the composition of the gut microbiota. Among these, diet [113, 114], alcohol consumption [115], smoking [116], and changes in circadian rhythm [117] have been shown to affect the microbiota composition. The negative effects of antibiotics can be contrasted by the concomitant treatment with probiotics. Nevertheless, the development of antibiotics with selective antimicrobial action is desirable. A crucial factor is therefore the identification of the gut microbiota associated with the disease. At present, there are no definitive data on which types of gut microbiota are altered in AD. Thus, the future of antibiotics as therapeutics in AD depends on the research progresses in the role of gut microbiota.

Preclinical studies can certainly help to answer these questions. The manipulation of germ-free animals with various bacterial strains present in gut microbiota could provide specific indications on the possible therapeutic targets related to AD. At that point, one can think of inducing gut microbiota modifications with the use of pre-, pro-, or antibiotics to obtain beneficial effects.

2. Host Immune–Microbiota Interactions

Initially, microbes were viewed solely as pathogens that cause and propagate infectious diseases. Nowadays, it is well established that human beings harbor microbial communities with key beneficial health functions. Indeed, most of these microbes are commensal and play an important role in our metabolism, mediating food digestion, and in the development and polarization of immune responses, preventing pathogens from invading our body [25]. The microbiota, namely the microbial communities harbored by the host, outnumber human cells by a factor of 10 and encode hundreds of genes that are absent in the human genome [28].

The human immune system and gut microbiota clearly interact with each other in such a way that one shapes the other to a large extent. The immune system plays a crucial role in protecting humans from invading pathogens and in maintaining the self-tolerance. However, in the case of autoimmunity, the breakdown of physiological mechanisms responsible for maintaining tolerance to self-antigens leads the immune system to attack the body’s own tissues. It has been suggested that dysbiosis may affect autoimmunity by altering the balance between tolerogenic and inflammatory members of the microbiota and, therefore, the host immune response.

The human immune system has developed different mechanisms to tolerate commensal microbes and prevent pathogens invading the host [29]. In this respect, the microbiota increases the epithelial barrier function through the production of different metabolites, such as short-chain fatty acids (SCFAs) and mucus. The microbiota also promotes the production of antimicrobial molecules such as regenerating islet-derived protein III (REGIII)-γ and REGIII-β by epithelial cells in the intestine [29]. Researchers report that germ-free mice and mice treated with broad-spectrum antimicrobials showed a reduced proliferation of intestinal epithelial cells (IECs) and also a lower production of antimicrobial peptides [30,31]. Furthermore, this host–microbiota relationship also ensures the establishment of immune homeostasis so that the host’s immune system does not attack the commensal microbes. Pattern-recognition receptors (PRRs), including TLRs, located on IECs and also on antigen presenting cells (APCs) at the interface between the host and microbiota, recognize and integrate signals from microbial associated motifs and regulate intestinal barrier function and immune responses [23]. The inflammatory response triggered by TLR signaling can be further controlled either by intracellular regulators, which can inhibit TLR signaling pathways, or by the production of anti-inflammatory cytokines that are also modulated by the microbiota [29]. In addition, several studies have found that different functions of macrophages, dendritic cells and neutrophils, which are an essential part of the innate immune system, are modulated by the microbiota [32,33]. Furthermore, the gut microbiota seem to play a critical role in differentiating a second type of Natural Killer (NK) cells (IL-22 + NKp46 + ) which belongs to the group of innate lymphoid cells (ILCs) with an important role in regulating homeostasis and inflammation [34].

Other studies also support a role of the gut microbiota in the development and function of the adaptive immune system. Specific microbial groups are associated with the initiation of specific T cell responses for instance, Bacteroides fragilis induces the differentiation of Treg cells, promoting an anti-inflammatory immune response [35]. Furthermore, Clostridium spp., belonging to clusters IV and XIVa, have also been associated with the differentiation of CD4 + T cells into IL-10 producing-Treg cells in the germ-free mice intestinal mucosa, colonized with a specific bacterial mixture of clostridia [36]. Segmented filamentous bacteria (SFB) comprise a group of Gram-positive clostridia-related bacteria that strongly stimulate immune responses. Indeed, SFB have been associated with a pro-inflammatory response, inducing the differentiation of naïve CD4 + T cells into Th17 cells [37]. SFB mediate a state of controlled inflammation, which primes the gastrointestinal tract to be ready for pathogen invasion, thus protecting the host against acute infections (e.g., Citrobacter rodentium, a bacterial pathogen affecting animals that causes acute intestinal inflammation similar to enteropathogenic Escherichia coli (EPEC) in humans) [37]. However, SFB colonization could also lead to adverse host effects. SFB can therefore be considered as examples of pathobionts, which are potentially pathogenic microorganism comprising the indigenous microbiota but that may contribute to disease under certain circumstances (triggered by environmental or genetic factors), possibly involving increased numbers or adaptive mutations [38,39,40,41]. Therefore, the specific host genetic makeup and environmental factors could contribute to promoting or preventing the colonization of particular microorganisms, influencing their numbers and virulence features, thereby shaping a pro-inflammatory or anti-inflammatory intestinal milieu. CD is well characterized by an upregulated Th1 immune response (increased IFN-γ) and consequently a Th1 polarized inflammation even observed in patients following a GFD. Recent studies have suggested that the increased expression of Th1 cytokines observed in CD may have partly resulted from the microbiota imbalance and/or the altered expression of PPRs which could play a role in shifting responsiveness towards Th1-type immunity [8,42,43]. Human genetics and host-associated microbial communities have been related independently to a wide range of chronic diseases, including CD. We now know that environmental factors and host genetics interact to regulate microbiota acquisition and to maintain healthy gut microbiota stability [44,45]. In turn, these three components seem to interact strongly, maintaining gut integrity and immune gut homeostasis. The disruption of gut integrity and disturbance of immune gut homeostasis caused by modifying one or more of the three interacting components may trigger the development of diseases such as CD ( Figure 1 ) [46].

Proposed model for celiac disease (CD) pathogenesis. Specific host genetic makeup and environmental factors could promote the colonization of pathobionts and reduce symbionts, thus leading to dysbiosis. Dysbiosis may contribute to disrupting the immune homeostasis and gut integrity, thereby favoring CD onset and aggravating the pathogenesis.

Who will benefit?

The study will benefit adults and children diagnosed with celiac disease and gluten-related disorders, and those at risk for these conditions. The study will lay the foundation for further significant research on celiac disease.

In addition, celiac disease is the only autoimmune condition for which the trigger has been identified (gluten), so scientists working in related health fields closely follow developments in celiac disease and use them to gain understanding of other autoimmune conditions.

Preventing Peritonitis

For select people with cirrhosis and ascites, the doctor may prescribe antibiotics to prevent peritonitis.

Although peritonitis can be a complication of peritoneal dialysis, it's much less common than it used to be because of improved technology and self-care techniques that are taught during initial training.

If you're receiving peritoneal dialysis, you can lower your risk of peritonitis by following these tips:

  • Thoroughly wash your hands, including the areas between your fingers and under your fingernails, before touching the catheter.
  • Wear a mouth/nose mask during exchanges.
  • Observe the proper sterile exchange technique.
  • Apply an antibiotic cream to the catheter exit site every day.

Immediately report any possible contamination of your dialysis fluid or catheter to your peritoneal dialysis nurse. In many cases, a single dose of antibiotics can prevent a contamination from turning into an infection.


National Health Service (U.K.): "Peritonitis."

American Association of Kidney Patients: "What Are the Signs and Symptoms of Peritonitis?" "Peritoneal Dialysis - Safe, and Perhaps Easier Than You Think."

Urgent Identification and Management of Postsplenectomy Sepsis

Urgent message: Asplenic individuals have a rate of severe infections 2-3 times higher than the general population. Postsplenectomy sepsis should be considered in patients with impaired splenic function who present with a fever.

Megan L. Lawson, PA-C and Christina Gardner, DHSc, MBA, PA-C


A 45-year-old male presented to the urgent care with 18 days of sinus pain and congestion unresponsive to two courses of antibiotics, cefdinir and levofloxacin. Past surgical history revealed a splenectomy 20 years ago after a motor vehicle accident. Physical exam showed a temperature of 100.5°F and a heart rate of 114 BPM. Patient was well-appearing with normal heart and lung exams. He had mild frontal sinus tenderness.


Individuals with impaired splenic function are at significant risk for severe infections leading to sepsis, with the risk being highest in the first 1-2 years postsplenectomy, but persisting lifelong. 1 Huebner and Milota opine that there is an opportunity for knowledge acquisition for primary care providers, who do not commonly see the devastating sequelae of missed diagnoses. 2


The spleen is the largest collection of lymphoid tissue in the body and plays an important role in immune function, both in terms of innate immunity (ie, the body’s natural, nonspecific defense mechanisms) and acquired immunity (immunity resulting from exposure to an agent).

The immune function of the spleen is to help clear encapsulated bacteria from the body, primarily Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b. 3,4 The spleen is also important for clearing intra-erythrocytic parasites like Babesiosis and Plasmodium falciparum (which causes malaria). 4

Another important immune function of the spleen is to help produce IgM, which is important for the initial clearance of organisms from the body. 3,5 Consequently, asplenic individuals have a decreased response to polysaccharide vaccines and need more frequent boosters than the general population. 5,6 Asplenic individuals are more susceptible to severe infections, with a rate two-to-three times higher than the general population. 7

Sepsis is defined as “life-threatening organ dysfunction caused by a dysregulated host response to infection.” 8 Postsplenectomy sepsis is sepsis occurring any time after removal of the spleen.

The lifetime risk of postsplenectomy sepsis is about 5%. The risk for developing sepsis varies with patient population and depends on the individual’s age, indication for splenectomy, and whether they have any additional ongoing immunosuppression. There is a higher risk if the splenectomy was due to a hematological disorder as opposed to trauma. 3 The greatest risk for developing postsplenectomy sepsis appears to be within the first 2 years after splenectomy, but this risk persists beyond that and likely lasts a lifetime. 3,6 The mortality rate for postsplenectomy sepsis ranges from 38% to 70%, even with adequate treatment. 3,5,6


Who Is at Risk?

Asplenia refers to complete loss of splenic function.

  • Anatomical asplenia can be due to either a congenital condition or surgical removal, while functional asplenia occurs when diseases, such as sickle cell disease, cause the spleen to have decreased or absent function.
  • Surgical asplenia following a trauma or for therapeutic purposes is the most common reason for asplenia. 1 There are approximately 25,000 splenectomies performed each year in the United States and the estimated number of asplenic individuals in the United States is around 1 million. 6
  • Congenital asplenia is rare. 6

Hyposplenia is an acquired disorder associated with many different disease processes. The most common causes of hyposplenia are chronic graft vs host disease after stem cell transplant, celiac disease, and untreated HIV. 5 It is estimated that 50% of these patient populations have some degree of hyposplenia. 5,6

Impaired splenic function in sickle cell disease begins manifesting at a very young age. Children under 3 years old are extremely susceptible to encapsulated bacteria, with risks 300─600 times higher than the general population’s. The incidence of hyposplenia in celiac disease ranges from 33% to 76%. According to Di Sabatino, et al, the development of hyposplenia in this population appears to be related to gluten exposure prior to diagnosis. A gluten-free diet can sometimes restore splenic function—if there has not been irreversible loss of splenic tissue. Bone marrow transplantation is associated with hyposplenia 15%–40% of the time. The pathophysiology driving hyposplenia in these conditions is not well understood. 5

While all patients with anatomic asplenia are at risk for severe infections, it is not as easy to determine the risk in patients with functional asplenia and hyposplenia because their splenic function is so variable.

The best way to determine splenic function has not been established. The gold standard for assessing splenic function is to count pitted erythrocytes however, because of the specific equipment needed for this, it is rarely used in clinical practice. Most commonly, detection of Howell─Jolly bodies on peripheral blood smear is used, but the sensitivity and specificity of this have been questioned, especially in milder forms of hyposplenia. Because of the difficulty in assessing splenic function, patients with functional asplenia and hyposplenia are typically treated like patients with anatomic asplenia when they present with signs and symptoms of a severe illness or fever. 5


Postsplenectomy sepsis often presents as a mild flu-like illness with fever, chills, sore throat, headache, muscle aches, vomiting, and/or diarrhea that can be hard to distinguish from other disease processes. 3 Fever in an asplenic patient should be taken seriously, as it could be the first sign of an infection that could rapidly progress to sepsis. Asplenic patients presenting without a fever, but who appear toxic, should also be treated very aggressively. 6 It is also important to remember that sepsis can present with a low body temperature, typically defined as less than 36°C. 8

The most common foci of sepsis in asplenic individuals are the respiratory tract, abdominal cavity, and central nervous system however, much of the time no focus is found. 9 While a healthy individual with a functioning spleen may take days to decline, asplenic patients can deteriorate within hours. 6 There is a high incidence of shock, hypoglycemia, acidosis, electrolyte abnormalities, respiratory distress, and disseminated intravascular coagulation in the asplenic patient population. 3


Individuals with impaired splenic function who present with fever and/or severe illness should be transferred to the emergency department for further evaluation. 2

Early administration of broad-spectrum antibiotics is the most important action to decrease mortality from postsplenectomy sepsis. 3,4 Early goal-directed therapy including fluid resuscitation, vasopressor management, and airway management, in addition to early empiric antibiotics, has the potential to reduce mortality from postsplenectomy sepsis by 30% to 60%. 3

Preventing Infection

Studies have demonstrated poor compliance among healthcare providers with the recommendations and guidelines for asplenic patients, especially in the outpatient setting. 1,2 Asplenia and hyposplenia are often overlooked as causes of immunocompromise, which places patients at risk for developing severe infections and subsequent sepsis. There are three main categories of recommendations that focus on prevention of postsplenectomy sepsis: patient education, vaccination, and empiric antibiotics.


Patients who have impaired splenic function should be informed about their lifelong increased risk of infection and educated about the signs and symptoms of infection and sepsis, as this education has been shown to reduce incidence. 1,4,10 A 2004 study by El-Alfy and El-Sayed demonstrated rates of postsplenectomy sepsis to be 1.4% among patients deemed to have good knowledge about their condition, versus 16.5% among patients who had poor knowledge. 10

Patients should also be informed about the risk of animal bites and traveling overseas, as these increase the risk of severe infection in asplenic and hyposplenic patients. Dog bites in asplenic individuals can be associated with sepsis from Capnocytophaga canimorsus. Patients with impaired splenic function are also at increased risk of developing a severe malarial infection, so malaria prophylaxis is very important if patients are traveling to endemic areas. Most sources recommend patients with impaired splenic function seek expert consultation prior to traveling. 1 Patients without a functioning spleen are also at risk for severe tick-borne illnesses, including Babesiosis, necessitating that patients be counseled on how to avoid tick bites. 4


There are three vaccines that target infections asplenic patients are especially prone to: pneumococcal, Hib, and meningococcal (see Table 1). The timing of vaccination will depend on whether the splenectomy is elective or emergent. There is some evidence to suggest that administration of the vaccines in the 2 weeks prior to or the 2 weeks after splenectomy can impair the body’s immune response. 6 If the splenectomy is elective, patients should start the vaccine series at least 2 weeks prior to the procedure 1 if the splenectomy is emergent, the series will typically not be initiated until at least 2 weeks after the splenectomy. 6

Table 1. Vaccination Recommendations 1,6

OrganismPrimary VaccinationsBoosters
Initial8 weeks later
PneumococcusPCV13 (conjugate)PPSV23 (polysaccharide)PPSV23 booster every 5 years
Haemophilus influenzae type bConjugate Hib None
MeningococcusConjugate ACWY2 nd dose of conjugate ACWYBooster every 5 years
Recombinant B+2 nd dose of recombinant B+None
InfluenzaInfluenza vaccine Annually

There are two vaccines recommended to protect against Pneumococcus: Prevnar 13 (conjugate vaccine) and Pneumovax 23 (polysaccharide vaccine). Current recommendations are to start with the conjugate vaccine (Prevnar 13) and give the polysaccharide vaccine (Pneumovax 23) 8 weeks later. This sequence improves antibody concentrations because asplenic individuals have a decreased immune response to polysaccharide vaccines. 4,6 The polysaccharide vaccine should be re-administered every 5 years because antibody concentrations decline in asplenic individuals over this time period. 11 The Hib vaccine is recommended in patients who did not previously receive it as a child. 6

There are two vaccines recommended for protection against Meningococcus: Conjugate ACWY and Recombinant B+. Both require two doses separated by 8 weeks. The conjugate vaccine should be re-administered every 5 years while the recombinant vaccine does not require any boosters. It is also recommended for patients to get a yearly influenza vaccine, as influenza infection can predispose them to secondary bacterial infections with Streptococcus pneumonia and Staphylococcus aureus. 1


All asplenic individuals should have a supply of antibiotics to take empirically if they develop signs of infection and cannot get to a medical facility in a timely manner, to prevent the development of clinical sepsis. 6 Patients should be educated to go to a medical facility for evaluation if they develop fever, malaise, chills, or other constitutional symptoms. If they cannot get to a medical facility that can administer parenteral antibiotics within 2 hours, they should take a dose of the antibiotic they have on hand. All guidelines recommend empiric antibiotics in these cases, and patients should receive empiric antibiotics whether or not they are already receiving prophylactic antibiotics (discussed below). The chosen antibiotic should target encapsulated organisms, as these are the most common culprits in postsplenectomy sepsis. The most common regimens are amoxicillin or amoxicillin/clavulanic acid and, alternatively, levofloxacin or moxifloxacin if the patient has a penicillin allergy. 1,6

A more controversial topic is the concept of prophylactic antibiotics, which are taken on a daily basis to prevent infection. Some sources recommend lifelong antibiotic prophylaxis in everyone with impaired splenic function, but the general consensus seems to be that only certain populations require long-term prophylaxis, including the first 3 years postsplenectomy, children under 5 years old, and anyone who has survived an episode of postsplenectomy sepsis. 1,2,6 The standard regimen for prophylactic antibiotics is penicillin because it is inexpensive, well-tolerated, and effective against encapsulated bacteria. 4

Patients with impaired splenic function are commonly encountered in the urgent care setting, and the immunosuppressive nature of this disease is often overlooked. The warning signs for impending sepsis may be subtle in this patient population, so it is important to be especially cognizant of abnormal vital signs like fever and tachycardia. It is also imperative to be aware of the conditions that predispose individuals to impaired splenic function, like sickle cell disease, celiac disease, HIV, and stem cell transplantation, because many patients with impaired splenic function are unaware of their condition. The management and disposition differs for individuals with impaired splenic function compared to otherwise healthy individuals.

The three most important aspects of preventing postsplenectomy sepsis are patient education, vaccination, and the use of empiric antibiotics. It is not uncommon for patients who do not have a primary care provider to seek care in the urgent care setting, so implementing these prevention strategies may fall solely on the urgent care provider.


The case presented at the beginning of this article concerns a patient who is clearly at risk for developing postsplenectomy sepsis. Red flags are that he had already completed two rounds of oral antibiotics without improvement and the fact that he is febrile and tachycardic. This patient was transported to the emergency department, then admitted to the progressive care unit for 5 days. He received IV antibiotics and his symptoms gradually started to improve, but no focus of infection was found. He was discharged home on PO antibiotics.

  1. Kanhutu K, Jones P, Cheng AC, et al. Spleen Australia guidelines for the prevention of sepsis in patients with asplenia and hyposplenism in Australia and New Zealand. Intern Med J. 201747(8):848-855.
  2. Huebner ML, Milota KA. Asplenia and fever. Proc (Bayl Univ Med Cent). 201528(3):340-341.
  3. Sinwar PD. Overwhelming post splenectomy infection syndrome – review study. Int J Surg. 201412(12):1314-1316.
  4. Buzele R, Barbier L, Sauvanet A, Fantin B. Medical complications following splenectomy. J Visc Surg. 2016153(4):277-286.
  5. Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. The Lancet. 2011378(9785):86-97.
  6. Rubin LG, Schaffner W. Care of the asplenic patient. New Engl J Med. 2014371(4):349-356.
  7. Kristinsson SY, Gridley G, Hoover RN, et al. Long-term risks after splenectomy among 8,149 cancer-free American veterans: a cohort study with up to 27 years follow-up. 201499(2):392-398.
  8. Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (sepsis-3). 2016315(8):801-810.
  9. Theilacker C, Ludewig K, Serr A, et al. Overwhelming postsplenectomy infection: a prospective multicenter cohort study. Clin Infect Dis. 201662(7):871-878.
  10. El-Alfy MS, El-Sayed MH. Overwhelming postsplenectomy infection: is quality of patient knowledge enough for prevention? Hematol J. 20045(1):77-80.
  11. Boam T, Sellars P, Isherwood J, et al. Adherence to vaccination guidelines post splenectomy: a five year follow up study. J Infect Public Health. 201710(6):803-808.

Megan L. Lawson, PA-C is an urgent care medicine provider for Carilion Clinic. She completed the ACP Fellowship in Urgent Care and Rural Health at Carilion Clinic. Christina Gardner, DHSc, MBA, PA-C is the Fellowship Director for the ACP Fellowship in Urgent Care and Rural Health an urgent care medicine PA for Carilion Clinic and Director of Clinical Education for the Radford University Carilion PA Program. The authors have no relevant financial relationships with any commercial interests.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Do not inject Humira into skin that is bruised, red, tender, or hard.

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

Do not receive a "live" vaccine while using adalimumab. The vaccine may not work as well during this time, and may not fully protect you from disease. Live vaccines include measles, mumps, rubella (MMR), polio, rotavirus, typhoid, yellow fever, varicella (chickenpox), or zoster (shingles).


Although there has been a substantial increase in the number of CD diagnoses over the last 30 years, many patients remain undiagnosed [187]. The flow-chart for identifying CD in adults must always include both serology and intestinal biopsy, whereas genetics should be performed only in selected cases. Diagnostic criteria should help physicians in avoiding misdiagnosis and missing cases of CD (i.e., seronegative patients with classic symptoms not undergoing biopsy) and preserve people from an unjustified GFD. The treatment for CD is still primarily a GFD, which requires significant patient education, motivation, and follow-up. Slow response occurs frequently, particularly in people diagnosed in adulthood. Persistent or recurring symptoms should lead to a review of the patient’s original diagnosis, exclude alternative diagnoses, evaluation of GFD quality, and serologic testing as well as histological assessment in order to monitor disease activity. In addition, evaluation for disorders that could cause persistent symptoms and complications of CD, such as refractory CD or lymphoma, should be pursued. The future opens to new therapeutic and preventive strategies, which are expected to improve the patient’s quality of life and pave the way to a definitive cure for this old disease.

Box 1 Causes for the increased number of intraepithelial lymphocytes in the intestinal mucosa with normal villous architecture

Non-celiac gluten sensitivity

Food allergies (cereals, milk proteins, soy derivatives, fish, rice, chicken)

Infectious (viral enteritis, Giardia, Cryptosporidium, Helicobacter pylori)

Bacterial contamination of the small intestine

Drugs (e.g., non-steroidal anti-inflammatory drugs)

Immune system diseases (Hashimoto’s thyroiditis, rheumatoid arthritis, systemic erythematosus lupus, type 1 diabetes mellitus, autoimmune enteropathy)

Common variable immune deficiency

Chronic inflammatory intestinal diseases (Crohn’s disease, ulcerative colitis)