Toxic shock syndrome & Streptococcal toxic shock syndrome(STSS)! Ahaa confused

 

Toxic shock syndrome (TSS), mediated by enterotoxins produced by Staphylococcus aureus or Streptococcus pyogenes.Generally when we say TSS we mean Toxic shock syndrome caused by Staphylococcus aureus & only when we specify it as STSS we mean Toxic shock syndrome caused by Streptococcus pyogenes.

Clinical case definition of TSS

An illness with the following clinical manifestations:

• Fever: temperature greater than or equal to 102.0°F (greater than or equal to 38.9°C)
• Rash: diffuse macular erythroderma
• Desquamation: 1-2 weeks after onset of illness, particularly on the palms and soles
• Hypotension: systolic blood pressure less than or equal to 90 mm Hg for adults or less than fifth percentile by age for children aged less than16 years; orthostatic drop in diastolic blood pressure greater than or equal to 15 mm Hg from lying to sitting, orthostatic syncope, or orthostatic dizziness
• Multisystem involvement (three or more of the following):
  • Gastrointestinal: vomiting or diarrhea at onset of illness 
  • Muscular: severe myalgia or creatine phosphokinase level at least twice the upper limit of normal
  • Mucous membrane: vaginal, oropharyngeal, or conjunctival hyperemia
  • Renal: blood urea nitrogen or creatinine at least twice the upper limit of normal for laboratory or urinary sediment with pyuria (greater than or equal to 5 leukocytes per high-power field) in the absence of urinary tract infection
  • Hepatic: total bilirubin, alanine aminotransferase enzyme, or asparate aminotransferase enzyme levels at least twice the upper limit of normal for laboratory
  • Hematologic: platelets less than 100,000/mm³
  • Central nervous system: disorientation or alterations in consciousness without focal neurologic signs when fever and hypotension are absent.

 

Staphylococcal TSS presents with a triad of fever, scarlitiform rash and cardiovascular collapse

 

In the early 1980s, the incidence of staphylococcal TSS among healthy, young, menstruating women increased. Eventually, it was discovered that a specific manufacturing defect in tampons linked staphylococcal TSS to their use. The tampons were believed to neutralize the acidic vaginal environment during menstruation, thus promoting oxygen tension and raising carbon dioxide levels in the vagina, providing a proper medium for the growth of S aureus.[reference from emedicine]

 

Case definition for streptococcal TSS :

1. Isolation of group A Streptococcus from a normally sterile site (ie, blood, cerebrospinal fluid, pleural or peritoneal fluid)
2. Hypotension
3. Two or more of the following:
   1. Renal impairment: Creatinine greater than or equal to 2 mg/dL (greater than or equal to 177 µmol/L) for adults or greater than or equal to twice the upper limit of normal for age. In patients with preexisting renal disease, a greater than twofold elevation over the baseline level.
   2. Coagulopathy: Platelets less than or equal to 100,000/mm³ (less than or equal to 100 x 10⁶/L) or disseminated intravascular coagulation, defined by prolonged clotting times, low fibrinogen level, and the presence of fibrin degradation products.
   3. Liver involvement: Alanine aminotransferase, aspartate aminotransferase, or total bilirubin levels greater than or equal to twice the upper limit of normal for the patient's age. In patients with preexisting liver disease, a greater than twofold increase over the baseline level.
   4. Acute respiratory distress syndrome: defined by acute onset of diffuse pulmonary infiltrates and hypoxemia in the absence of cardiac failure or by evidence of diffuse capillary leak manifested by acute onset of generalized edema, or pleural or peritoneal effusions with hypoalbuminemia.
   5. A generalized erythematous macular rash that may desquamate.
   6. Soft-tissue necrosis, including necrotizing fasciitis or myositis, or gangrene.

The following risk factors have been reported to be associated with STSS:

• Patients with HIV, diabetes, cancer, ethanol abuse, and other chronic diseases
• Patients with a recent history of varicella infection (chicken pox)
• Patients who used nonsteroidal anti-inflammatory drugs (NSAIDs)

Differntiate between TSS & STSS clinically & lab studies:

Differentiating between staphylococcal and streptococcal TSS is often difficult at the initial presentation. On the other hand, there appears to be some symptoms and signs that may assist in distinguishing between the 2 etiologies.

1. Patients with staphylococcal TSS tend to present with diarrhea, vomiting, generalized erythroderma, conjunctival injection, and/or severe myalgia.
2. Patients with streptococcal TSS, however, often have a form of soft tissue necrosis (eg, cellulitis, abscess, myositis, or necrotizing fasciitis), influenza-like symptoms, and (as previously described) varicella in those patients who have not been vaccinated against it.

 

Laboratory tests are often the only way to distinguish between the 2 etiologies. As previously mentioned, both types of TSS are mediated by enterotoxins.

• In staphylococcal TSS, toxic shock syndrome toxin–1 (TSST-1) is responsible for nearly 75% of cases. Testing for this toxin involves detecting the presence of antibodies against it. If TSST-1 antibodies are present in the laboratory studies, the specificity of TSS being caused by S aureus is up to 90%.
• S pyogenes TSS, on the other hand, is mediated by different enterotoxins, but all are linked to the M-protein found in the cell membrane of the bacterium. Streptococcal pyrogenic exotoxins (SPEs) A, B, and C are present in only about 13% of S pyogenes–mediated TSS-related cases; however, laboratory testing suggests that the M-protein is present in about 75% of these cases. Unfortunately, no reliable tests detecting M-protein exist at this time. Streptolysin O, however, is another toxic immunogenic protein produced by S pyogenes. Its presence during an infection can be measured using the titer against antistreptolysin antibody (ASO titer). The sensitivity of this test ranges from 62-76%, with a specificity of 79-85%; therefore, elevated titer levels will often identify S pyogenes as the etiologic bacterium.

TREATMENT:Regardless of the bacteria causing TSS, the treatment remains the same.

Crystalloids and inotropic agents are used to aggressively treat the hypovolemic shock, with close monitoring of the patient's mean arterial pressure (MAP) and central venous pressure (CVP).

Furthermore, targeted antibiotics are indicated;

• penicillin or a beta-lactam antibiotic is used for treating group A streptococci, and
• vancomycin or a semisynthetic antistaphylococcal penicillin is used for staphylococcal TSS.
• Clindamycin(800 mg IV every 8 hours), however, has emerged as a key portion of the standard treatment. When utilized, clindamycin has an 83% more favorable outcome when compared with penicillin or beta-lactam antibiotics (14%). As opposed to penicillin, clindamycin is not affected by the size of the inoculum, it has a longer postantibiotic effect, and it better facilitates phagocytosis by inhibiting the production of the antiphagocytic M-protein. In addition, clindamycin reduces TSST-1 levels by up to 90%, whereas penicillin or other beta-lactam antibiotics have the potential to raise TSST-1 levels because they will lyse or alter the bacterial cell membrane, which often causes further release of the toxin into the bloodstream.clindamycin often is considered the drug of first choice for invasive group A streptococcal infections such as STSS

Lepromin test & Dharmendra antigen

Skin test with lepromin is the only in vivo immunological skin test used as an aid to the classification and prognosis of leprosy

Lepromin test:

• The Iepromin test was first described by Mitsuda in 1919
• this test used intradermal injection of a lepromin ( Dharmendra or Mitsuda antigen), to classify the stage of leprosy based on the lepromin reaction (Fernandez or Mitsuda reaction); it differentiates tuberculoid leprosy, in which there is a positive delayed reaction at the injection site, from lepromatous leprosy, in which there is no reaction (a negative test result) despite the active malignant Mycobacterium leprae infection

Two types of antigens are in use—Mitsuda and Dharmendra lepromins

The Lepromin lest could be compared lo the Tuberculin lest since it is also a skin test intended to assess the delayed types of hyper sensitivity (DTH) due to a specific infection. However, there are certain basic differences in the nature of antigen between Tuberculin and Lepromin.

1. Tuberculin is a culture filtrate of tubercle bacilli. Since leprosy bacilli cannot be cultured, lepromin is a suspension of whole or partially defattened leprosy bacilli killed generally by heat,
2. Secondly, since the only source of leprosy bacilli is the human or armadillo host, contamination by the host tissue is unavoidable despite all the attempts to purify the organisms from the tissue contamination

The original Mitsuda antigen — the crude or integral lepromin — is prepared by grinding the tissues rich in bacilli in 0.5% carbol saline, the larger particles being removed by filtration. The lepromin is standardized by the weight of the whole tissue. It is obvious that lepromin prepared by this method would contain a considerable proportion of human tissues, Fernandez and Castro purified the integral lepromin by differential centrifugation, but the yield of bacilli by this method was not high.

The lepromin extensively used in India is the one prepared according to the method described by Dharmendra (1967) in which the organisms arc extracted from the tissues with chloroform. The lepromin thus prepared is comparatively free of host (issues, but the bacilli are partially defatted on account of the chloroform used). The standardization of Dharmendra lepromin is also by weight, 10 mg of dried bacillary powder being dissolved in 100 ml carbol saline

• It is chloroform-ether extracted suspension of Mycobacterium leprae; used to produce the lepromin test.
• Dharmendra antigen is a suspension of de­fatted leprosy bacilli first reported by Dharmendra in 1941-1942. But it was fur­ther standardised by bacterial count by Sengupta et al 1979. This antigen evokes an early as well as late reaction with an intrad­ermal dose of 0.1ml.

Method

0.1 ml of lepromin is injected intradermally usually on the fore-arm. Positive reaction is observed at two different times—48 hours and 21 days after the injection.

Early reaction (Fernandez) :The 48 hour reaction or the early reaction is seen as a wheal with slight edema and-induration. The diameter of the wheal and induration is measured by a pair of calipers. The reaction is a manifestation of the classical delayed type hypersensitivity and is weak with Mitsuda lepromin. Induration of 5 mm and above with erythema of 10 mm or more was considered as positive.

late reaction (Mitsuda) :The 21 day reaction or the late reaction is seen as a local induration of skin producing a nodule like firm swelling. In a strong reaction the nodule often ulcerates. The diameter of the induration is measured. The reaction is strong with Mitsuda lepromin but weak with Dharmendra preparation. On histological examination, the nodule shows collections of numerous lymphocytes with epithelioid cells and occasionally giant cells. The picture corresponds to that of tuberculoid type of leprosy

Lepromin reaction in cases of leprosy

The positivity of Lepromin test runs parallel with the Cell Mediated Immunity. Therefore, it is strongly positive in cases of Tuberculoid leprosy and negative in lepromatous leprosy. On the Borderline and Intermediate types it has an intermediate response, and various according to the C.M.I.

The present concept of leprosy is that of an immunological spectrum—spreading from

• highly resistant Tuberculoid (TT)
• through the Borderline group :The Borderline group can further be divided into 3 types —
• the Borderline towards the Tuberculoid (BT),
• the truly Borderline (BB) and
• the Borderline towards the Lepromatous (BL).
• practically non-resistant Lepromatous (LL),

The above 5 groups in addition to a larger number of intermediate forms, show gradual gradation in the resistance from the Tuberculoid to the Lepromatous end.

The lepromin test shows a corresponding fall from the strongest reaction in Tuberculoid leprosy to the Negative response in lepromatous leprosy with variable degrees of positivity in the different types of Borderline cases.

It is obvious from the results of the lepromin test that the Tuberculoid (TT) type shows the highest host resistance, while the lepromatous type is “anergic” to the skin test and the Borderline group show varying degrees of positivity depending on their position in the immunological spectrum.

The anergic state of lepromatous leprosy is the most interesting phenomenon in leprosy which is not seen in other diseases.

In tuberculosis at any rate, there is no condition parallel to lepromatous leprosy. There is thus perhaps an immune paralysis in lepromatous leprosy which accounts for the extremely large number of bacilli much greater than the number of bacilli found in the tissues of even moribund cases of tuberculosis. Thus the anergy in lepromatous leprosy seems to be a distinctive feature.

Significance of Lepromin test in cases of Leprosy

• The most important significance of lepromin test is in its application in classification of the disease.
• While in a good number of cases, diagnosis is possible by clinical examination alone, a proper classification of the disease requires clinical and histological examination, assessment of bacterial load by skin smears, as well as by lepromin reaction.
• The lepromin reaction in different types of leprosy is indicated below:

Tuberculoid type (TT)	2+to3+
Maculo anaesthetic type (MA)	1 + to 2+
Indeterminate type (I)	Neg. ± or +
Borderline type (BT)	1 + to 2 +
(BB)	±or +
(BL)	Neg. or ±
Lepromatous type (LL)	Neg.

It is obvious that Lepromin cannot be used as a diagnostic test since the very malignant form of the disease, namely the lepromatous type as well as some of the intermediate groups are negative.

Even positive test has no significance since the test indicates a delayed hypersensitivity reaction to an exposure to M. leprae. As such it could be expected to be positive in a good proportion of persons living in endemic areas and also in contacts of leprosy patients who might have a sub-clinical infection without manifestation of the disease.

While it is not a diagnostic test, lepromin helps in assessing the prognosis of a case.

• Thus, a patient of the Indeterminate type of leprosy with negative lepromin test has a grave prognosis since it is likely to turn into the lepromatous variety.
• Similarly a patient with 2+lepromin test belonging to the Maculo-anaesthetic type or Borderline (BT) type has a favourable prognosis