endocrinopathies or may a pointer towards a group of disorders. So, these skin manifestations are important in differential diagnosis of many disorders.

Diabetes mellitus, hyperthyroidism, hypothroidism, disorders of adrenals and gonads are the main endocrinopathies having skin manifestations and at time these signs help in reaching a definite diagnosis.

Certain skin lesions such as hyperpigmentation,sclerederma, xanthomas, lipomas, increased muscle mass , vesico bullous eruptions, yellow or red paules, fungal or bacterial infection, alopecia etc need the exclusion of endocrinopathies.

INTRODUCTION:
Skin is a very good reflector of internal disease in general and endocrine diseases in particular. Specific skin lesions may reflect a variety of endocrine diseases as well as manifest secondary conditions underlying metabolic disturbances. A knowledge of the same makes the diagnosis of endocrine diseases easier, which avoids delay and difficulty in diagnosis.

A timely diagnosis and early treatment spares future complications and saves the patients from their avoidable suffering. It is important that an attempt should be made to review the available literature to familiarize the treating physicians about the importance of skin markers of endocrine diseases.

These disorders are diabetes mellitus and endocrine disturbances of thyroid , adrenals , gonads and others.


I. DIABETES MELLITUS
A. PRIMARY SKIN DISEASES ASSOCIATED WITH DIABETES MELLITUS
1. Diabetes demopathy (pigmented pretibial patches, skin spots): Lesion of diabetic demopathy are less than 1 cm and are red brown , atrophic macules on the anterior shins which may begin as papules . Capillary basement membranes appear to be thickened.
2. Necrobiosis lipoidica diabeticorum (NLD): MLD lesions also characteristically appear on the anterior shins and are oval, atrophic plaques that can reach several centimeters in size. They have a raised , erythematous border and a yellow � brown, waxy central atrophic area through which telangiectatic subcutaneous vessels are easily visible. These lesions may also ulcerate.
3. Disseminated granuloma annulare (GA): Multiple small, grouped erythematous to flesh-coloured papules, which coalesce into small plaques covering the entire body surface have been associated with diabetes mellitus. However, patients with GA, even if it is extensive, do not necessarily have diabetes mellitus.
4. Lipodystrophy.:
a. The Siep-Lawrence syndrome (and related disorders with lipodystrophy) may be cogential and include insulin- dependent diabetes mellitus, hypertricosis, hyperpigmentation, increased muscle mass and somatic growth elevated trglycerides and cirrhosis of the liver.
b. Local lipoatrophy or lipohypertropy may appear at sites of insulin injection. The mechanism is unclear.
5. Insulin resistance and acanthosis nigricans: May be associated with polycystic ovaries in young women (Type A) or with antibodies to insulin receptors and other autoimmune phenomena (Type B).
6. Bullous diabeticorum: Tense blisters that appear suddenly on apparently normal skin usually on the extremities may occur in diabetes. Histologically the blister may be intraepidermla . Lesions may tend to ulcerate.
7. Eruptivexanthomas are accumulations of lipid in macriphages to form widespread yellow to red papules, which may occur in a linear fashion in response to trauma (the Koebner Phenomenon). These lesions appear in patients with poorly controlled diabetes mellitus who have massive hypertriglyceridemia.
8. Sclerederma (adultorum of Buschke) is a rare condition seen in severe insulin- dependent diabetes in which there is thickening of the collagen in the dermis and deposition of acid mucopolysaccarides between collagen bundles. The lesions are broad areas of non-pitting edema and hardening of the skin, especially on the face, neck, and upper trunk.
9. Idiopathic hemochromatosis , a disorder of excessive iron storage, consists of a triad of hepatic cirrhosis, cardiac insufficiency and diabetes. There is striking hyperpigmentation due to increased melanin deposition in the basal layer of the epidermis.

B. SECONDARY SKIN DISORDERS.
1.) Candida infection of the skin and mucous membranes occur in similar locations as described in glucocoriticoid excess.
2.) Cutaneous bacterial infections, especially staphylococcal infection such as folliculitis furinculocis and frank abscess formation may occur in poorly controlled diabetes patients.
Opportunistic infection by fungal organisms such as Mucor and Rhizopus (Phycomycosis) are rare but are seen in diabetics. Such lesions may be fatal.

II THYROID
A. HYPERTHYROIDISM.
1. General features of hyperthyroidism include warmth, increased sweating flushing and a smooth velvety texture of the skin. In sever cases there may be generalized. hyperpigmentation.
2. Hair and nails: Hair may becomethin, fine, limp and oily. There is distal onycholysis (separation of the nail plate from the nail bed). characteristically starting on the fourth finger (plummer nail).
3. Pretibial myxedema (PTM) :Localised accumulations of acid mucopolysccharides (hyaluronic acid) appear as red to brown to yellow plaque, usually on the anterior shins. There is a �peau f orange� pebbly surface with dilated hair follicles and coarse hairs. Lesions are non-pitting, cool, non-tender and may be pruritic. PTM is seen with active Graves Diseaseas well as or euthyroid �burnt out� or treated patients. High long-acting thyroid stmultor )LATS) levels have been associated with PTM.
4. Thyroid acropachy: Diffuse thickening of the distal extremities, clubbing and periosteal new bone formation with characteristic perpendicular bone spicules are seen associated with Graves Disease, often with opthalmopathy and pretibial myxedema.
B. HYPOTHYROIDISM
1. Congential signs of hypothyrodism are shubtle and should be vanishing with the advent of newly started screening programs for hypothrroidsm. General features includes cool, pale, translucent, �alabaster� skin with a yellow hue. This colour and texture are due to decreased blood flow anaeia. infiltration with mucopolysaccharides, prolonged jaundice and / or cartoenmia. Sweating is reduced. Thermal instability and frank hypothermiaare accompanied by persistent cuits marmorata (purplish discoloration), a violaceous mottling in a vascular pattern. Umbilical hernia, short proximal limbs depressed nasal bridge and large tongue complete the picture of congential hypothyroidism.
2. Acquired hypothyroidism has many of the same general feature as seen in the congential disease. Children and adults, in addition have more prominent dry and scaling skin resembling ichthyosis. Sweating is minimal as the eccrine ducts become atrophic, Generalised myxydema make the skin puffy, pale and doughy with a non-pitting edema, espically noticeable around the face and eyelids due to the accumulation of acid mucopoly saccharides.
3. Hair:Scalp hair is lost in a generalized pattern. The remain scalp hair is coarse and dry. Loss of the lateral one third of the eyebrows. (St. Ann Sign) is characteristic. Pubic and axillary hair is spares. Children may get a paradoxical hypertrichosis of arms. back and legs which is reversible with treatment.

III. ADRENAL
A. HYPOADRENALISM (Adrenocortical insufficiency. Addition�s disease)
1. Patients gradually develop generalized hyperpigmentation, there is darkening of the aerolae, genital skin preexistent nevi, palmar and plantar creases and recent scars. Blue black pigment deposit are seen on the gum at the toot margin and on the hard palate. The etiology of hyperpigmentationis probably due to excessive secretion of melanocyte �stimulating hormone (MSH).

2. 2). Hair in pubic and axillary areas becomes sparse and nails may develop hyperpigmented and linear streaks.

3. 3). Vitiligo rarely occurs in patients with Addison�s disease.

B. HYPERASRENALISM
Pituitary cushing syndrome, adrenal tumors, ad autonomous nodlar adrenal hyperplasia may have features of androgen excess as well as of the glucocorticold excess.
Iatrogenic Cushing Syndrome, resulting from systemic or topical glucocorticosteroids, does not have the androgenic features.
a). Primary features of glucocorticoid excess
1. General features include plethora, telangiectasias and increased growth of fine, downy vellus hair, especially on the sides of the face. With prolonged exposure, there is generalized atrophy of the skin and easy bruisability.
2. Striae represents both dermal and epidermal atrophy and occur in areas of skin tension. They are pigmented and red to blue because the dermal and subcutaneous blood vessels show through the translucent and atrophic skin. In some cases, they may become hyperpigmented with melanin.
3. Steriod acne appears on the upper arem, chest and back as well as on the face. The lesions are actually perifolliclar, hyperkeratotic papules, althroug in late stages these may become pustular and comedonal. The erupt at the same stage of development.
4. Redistribution of subcutaneous fat to the cheeks, upper back, buttocks and abdomen is characteristic.
5. In pituitary disease of in syndromes of ectopic adrenocorticotropic hormone (ACTH) production, there may be hyperpigmentaton, such as seen in Addition�s disease.
6. The androgenic effects from weak adrenal androgens such as dehydropiandrosterone (which may be converted to more potent androgens such as testosterone and dihydrotestosterone) produce classic acne vulgaris as well as hirsutism and male pattern hair loss in women.
h. Secondary features of glucocorticoid excess
1. Tinea versicolor appear as scaly, oval macules and patches on the upper trunk, back and arms wit variable hyperpigmentation or hypopigmentation. it is due to a superficial colonization with the fungus. Malassezia furfur.
2. Candida (Monilia) infections of the skin and mucous membranes include buccal mucosa (thrush) vaginal mucosa, nails and surrounding tissues (onychomycosis and paronychia). Interdigital webs, corners of the mouth (perleche) and intertriginous folds (intertigo).
3. There is an increased occurrence of cutaneous bacterial infections with pustules, furuncles and abscesses especially caused by Staphylococcus aureus.

C. CONGENTIALADRENAL HYPERPLASIA (CAH)
1. Infancy, severe forms of CAH are caused by enzyme defects in the to the synthesis of cortisol and may have only mild cutaneous signs, primarily hyperpigmentation of genital skin from excessive pituitary production of ACTH or MSH or both.
2. In later childhood, early onset of pubic and auxiliary hair and acne are signs of androgen excess.
3. In postpubertal adult women and perhaps in some men �mild� (or �partial� or late onset�) forms of CAH are now being recognized primarily from their skin manifestation of severe late onset or persistent acne, hair loss and hirsutism in women.
Hirustism is defined as excessive hair in androgen-dependent areas , such as upper lip, chin, areolae, linea albha and upper inner thighs. Male pattern hair loss (androgenic alopecia) is thinning of the hair over the crown of the scalp with relative sparing of the sides and back. Affected hair are of smaller diameter and grow to shoter length before entering the resting phase and falling out.
The diagnosis of CAH is made by finding elevation of the hormone that the sustrate for the deficient enzyme (e.g 17-alpha-hydroxyprogesterone in 21 hydroxylase deficiency, II-deoxycortisolin II-hydroxylase deficiency and 17-alpha- hydroxypregnenolone in 3-beta-hydroxysteroid dehydrogenase deficiency). If levels are not elevated in basal blood samples, these may be found as abnormal responses to ACTH stimulation.

IV. GONADS
A. Androgen excess: from the ovary will cause the same skin manifestations of acne, hair loss, and/or hirsutism as described above. Rarely, ovarial tumors are the cause; most grequently, polycystic ovarian disease (PCOD) is the source of hyperandrogenemia from the ovary.
B. In gonadal dysgenesis: (Turner Syndrome), there may be a few special cutaneous features such as multiple brown �black acquired nevi, a double row of eyelashes and low W-shaped posterior hairline, short fourth (and often fifth) digits on the hands and feet with dysplasia or absence of nails hyperconvexity of finger nails and toenails.

V. MISCELLANEOUS
ENDOCRINE DISORDERS
A. Mucocutaneous candidiasis has been associated with muliple endocrinopathy syndrome of autoimmune disorders, including hypoparathyroidism, Addison�s disease, premature ovarian failure, diabetes and Hashimoto�s thyroiditis. Vitiligo complete loss of pigment in patches and alopecia areata patchy hair loss which may progress to total loss of scalp hair (alopecia totails) or of al body hair (alopecia universails) have also been seen in association with these endocrinopathies.
B. Alopecia has been reported in association with vitamin �D resistant rickets in a few well-studied families.
C. Multiple mucosal neuromas are found in the multiple endocrine neoplasia (MEN) syndrome in association with a marfanoid habitus, thick lips hig calcitonin levels, medullary carcinoma of the thyroid and phenochromocytoma.
D. The glucagonoma syndrome consists of a diffuse, scaly brightly erythematous rash made up of gyrate, serpiginous plaques with clear centers and superficial scales. The lesions tend to expand, thus the name necrolytic migratory erythema. Such lesion are seen in association with malignant neoplasms of the alpha cells of the pancreas and have regressed when the tumor has been surgically removed.
E. Acanthosis nigricans (AN) has been associated with a wide variety of endocrine disorders including. Cushing syndrome, pituitary tumours, acromegaly, Addisons�s disease and polycystic ovarian disease. Most cases of AN have underlying insulin resistance.

CLINICAL FOCUS
� Many endocrinopathies involve skin as primary or secondary complication.
� Skin is a very good reflector of systemic disorders including the endocrinal diseases.
� Diabetes mellitus is commonly associated with varied dermatological lesions.
� Thyroid disorder (hyper or hypo) involve skin through various mechanisms.
� Adrenal pathology is associated with various manifestation of skin and its appendages.
� Other uncommon endocrinopathies are also someway associated with dermatopathies.


CONCLUSION
Endocrinipathies are associated with a large number of skin markers. A perfect knowledge about the pointers is mandatory for an endocrinologist or a physician.

The services of a dermatologist will be of immense help in such a situation and hence ideally in case of doubt in any cases the opinion of the dermatologist should be obtained in the greater interest of proper, diagnosis and ideal patient care.

�SUPER VASMOL 33 WITH AYUR PRASH� POISONING � A CASE REPORT

Dr. B.K. Barik, Dr. Dinabandhu Sahu, Dr. Abhiram Behera, Dr. Pusparani Das

ABSTRACT

"Super Vasmol" a commonly used hair dye containing various chemical and herbal ingradients may produce severe local and systemic manifestation when ingested. The fatality is low, the incidence is rare. Here we are reporting a case of vasmol poisoning who was thoroughly investigated and followed up till complete recovery.

KEYWORDS:
Super Vasmol, PPD, Resorcinol, Gastritis, Angioneurotic oedema.

NTRODUCTION:

`"SUPER VASMOL 33 WITH AYURPRASH" is an emulsion hair dye containing Paraphenyl Diamine (PPD), Liquid Paraffin, Cetostearyl Alcohol, Sodium Lauryl Sulphate, EDTA Disodium, Resorcinol, Propylene glycol, Herbal extracts, preservatives and perfume.

Severe angioneurotic oedema, acute renal failure (PPD); oedema, haemolysis, methemoglobinemia in infants, blue black pigmentation (Resorcinol); Acute haemolysis (Propylene glycol); headache, vomiting, gastritis (EDTA) are the serious systemic manifestations when the dye is ingested besides the local allergic reactions observed when in contact with skin in few cases.

CASE REPORT:

A 20 year female alleged to consume 'Super Vasmol 33' on previous night at 10 PM presented with vomiting , dyspnoea, dysphagia, difficulty of speech and gross swelling of neck and face below the chin and mandible (both sides) and dark urination.

The Patient was admitted to the local hospital (after 8 hours of ingestion) with worsening of above mentioned symptoms and treated with injection hydrocortisone (200 mg), injection Chlorpheniramine maleate (1 Amp) injection Cefotaxim (1gm-2 vials), injection Deriphylline (1 Amp) , injection Ranitidine (1 Amp) and oxygen inhalation. As the patient did not improve he was referred to this hospital.

At the time of admission (12 hours after ingestion) the patient was severely dyspnoeic with semi opened mouth having gross swelling of tongue and oral mucosa with salivation. The lip and gums were swollen with black pigmentation, ulceration and bleeding. There was difficulty in speech and swallowing. The urine colour was greenish black and volume was 400 ml since 12 hours. There was swelling efface (submandibular, submental and parotid region) extending to neck.

On examination the temperature was 98.8�F, Pulse 88/minute, regular , BP 126/80 mm Hg, without any localized or generalized lymphadenopathy. There was no pallor, cyanosis or icterus except black pigmentation of lip and gum. Respiration rate was 24/min, regular with vesicular breath sound without any added sound. Heart sounds, were normal without any murmur. There was no neurological deficit. The pharynx could not be examined due to oedema and ulceration of tongue & oral cavity. P/A examination revealed soft abdomen without any organomegaly. The urine was greenish black in color with suppressed volume (400 ml -12 hours). Other systemic examination were normal.

Patient was treated with gastric lavage by normal saline, O2 inhalation, injection Adrenaline - 0.6 mg (starting dose), Injection Avil, Injection Hydrocortisone (100mg) 8 hourly, injection Pantoprazole OD, injection Frusemide, injection Deriphylline 8 hourly and Cefriaxone 1 gm I/V twice daily and Tiniba infusion 500 mg daily and intravenous fluid. Patient gradually improved 3rd day onwards with decrease in mucosal swelling and face & neck swelling. There was slow improvement of the voice, dysphagia, dyspnoea and throat pain. Pharyngeal examination revealed oral mucositis with inflamed postcricoid area and presence of slough in the pyriform fossa. Gradually the colour of urine changed from greenish black to normal with increased volume. The patient was able to take orally (from liquid to solid) with supportive treatment of Xylocaine viscus, antacids.

Early investigation report shows Hb- 10.2gm%, ESR - 28mm/1st hr, TLC-13,000, DC - N 92, EO, BO, L8, MO, RBS - 148mg%, B. Urea 58mg%, S. Creatinine - 2.3mg%, S. Sodium -138 mmol/L, S.Potassium - 3.8 mmol/L, S. Bilirubin - 2.8 mg/dl (Total) 1.6 mg/dl (Direct), SCOT - 852 IU/L, SGPT - 1100 ILJ/L, Alkaline Phosphatase 290IU/L. Urine examination shows proteinurea (+), Puscells 0-3 /HPF with granular and hyaline cast. Upper Gl endoscopy (on 4th day of admission) shows erosive gastritis.

On 10th day, the patient recovered fully. The investigation parameters were normal.

DISCUSSION:

The commonly used hair dye having multiple chemical ingredients cause various complications. The fatality is low and incidence of poisoning is rare.

PPD, one of the intermediate dye used in hair colour is associated with systemic toxicities like severe angioneurotic oedema, acute renal failure and rhabdomyolysis. Liquid paraffin, a saturated hydrocarbon can produce extremely rare hypersensitivity reaction and dermatitis. Cetostearyl alcohol, the combination of aliphatic alcohol and esters act as non-ionic surfactant can produce allergic and urticaria! reaction. Sodium lauryl sulphate, an anionic surfactant used as detergent and foaming agent act as direct irritant at high concentration to the skin. 1% may cause contact dermatitis with burning, redness, tightening of skin with painful fissure and lamellar exfoliation. 2% may produce painful oral desquamation. Resorcinol can produce oedema, haemolysis and methemoglobinaemia in infants with blue-black pigmentary chages.

EDTA (0.3gm%) in excess produce headache, vomiting and gastritis. Propylene glycol is relatively nontoxic, may cause acute hemolysis. In animal when injected causes haemoglobinuric acute renal failure. It has low oral toxicity. Absorption through intact skin is minimal but the application of Propylene glycol containing compounds to infants with large areas of desquamation (e.g. Silver Sulphadizine Therapy in Toxic Epidermal necrolysis) has resulted in cardio-respiratory arrest. The kidney excretes 45% of absorbed dose unchanged and the remainder is metabolized by hepatic alcohol dehydrogenase to lactate, acetate and pyruvate. Liver metabolism produces lactic acids, which enters the glycolytic pathway and after large exposure causes an anion gap and metabolic acidosis. Used as a vehicle in oral, injectable and topical preparations, signs of alcohol intoxication seen after intake of vitamins suspended in Propylene glycol. The compound may be absorbed and produce a rise in serum osmolarity. Contact dermatitis, erythematous oedematous plaque and hypersensitivity occurs. Primarily Propylene glycol is a CMS depressant in large doses and such doses may cause hypoglycaemia, lactic acidosis and seizure in susceptible patients.

Our patient who was attended within hours of ingestion presented with some degree of renal, hepatic and haemolytic features. Local reaction, orophayngeal involvement were profound along with erosive gastritis.

REFERENCES:

1. Goldfrank's Toxicologic Emergencies - 6th Edition, Year 1998, Page Nos. 476-r, 477T, 913-915, 1057-1058.
2. Medical Toxicology Diagnosis and Treatment of Human Poisoning - Mathew J. Ellenhorn, Donald G, Barceloux, Year 1998, Page Nos. 31,32, 36, 442, 528-530,809-810,906,964.
3. Clinical Management of poisoning and drug overdose, Haddad, Shannon & Winchester, 3rd edition, Year 1998, Page No. 1170.

ABSTRACT:
We report a case of Acute pancreatitis in a case of falciparum malaria. The incidence of other complications are common. The mechanism of this rare complication and its pathophysiology is reviewed. ( The Ind. Pract. 2005; 58(10): 649-651).

KEYWARDS:
Malaria (Plasmodium Falciparum Malaria), Complications, Acute Pancreatitis, Serum Amylase, Serum Lipase.

INTRODUCTION:
Malaria, a burning problem in tropical countries and a disease of global concern has a major preponderance in India affecting life of all ages and races. It complications are responsible for taking away a major fraction of patient death in our country. The acute and chronic complications are many. As far as falciparum malaria is concerned it has diverse life threatening complications. Acute pancreatitis is very rare but devastating complication of falciparum malaria which we have put as a case report.

CASE REPORT:
A 41 year old male presented in general medicine ward in October 2004 with history of fever of 5 days which was associated with chill and rigor. There was yellow coloration of urine and conjunctiva for 3 days and gradual decrease of urination for 2 days. There was 5-6 episodes of loose motions and vomiting and pain abdomen (confined to epigastic region) for 10 hours before admission. The patient was not an alcoholic. There was no previous such history of pain abdomen. There was no history of trauma to abdomen. He is not a known case of DM, HTN, SCD APD. There was no history of taking any drug.

On examination the patient was average built, conscious with moderate pallor moderate icterus with mild oedema (bilateral pedal) no lymphadenopathy with a pulse rare 92 per minutes, regular, BP 100/70 mm of HG, without any signs of dehydration. Abdominal examination revealed mild distension and diffuse tenderness maximum at epigastric area, smooth tender hepatomegaly ( 5 cm below the costal line) moderate non tender spenomegaly (3 cm below the left costal margin), mild ascites and diminished bowel sound. Cardiovascular system, respiratory system and other systemic examination revealed no abnormality.

INVESTIGATION
HB- 9.8gm%
TLC � 10,200/mm2
DC � N69%, E-1%, L30%, B0%, M0%
Widal test � Negative
Microfilaria � Negative
Serum Bilirubin � Total 13.3mg%, Direct 10.4%
RBS � 172mg%
SGOT � 11IU/L
SGPT � 138IU/L
Serum Alkaline Phosphatase � 110 IU/L
S. Urea � 106mg%
S.Creatinine � 4.2mg%
Serum Amylase � 2050 IU/L
Serum Lipase � 3050IU/L
Serum Ca++ - 7.2gm%
HBs Ag � Negative
HCV Ag � Negative
Malaria Parasite � Slide +ve
QBC � pfr (++)
ICT � pfr (+)

Ultrasonogram revealed hepatosplenomegaly and features of acute pancreatitis and mild ascites. CT scan of abdomen also revealed hepatosplenomegaly ascites and acute pancreatitis.

On the basis of blood report patient was treated along the line of complicated malaria with artesunate, injection cefipime, metronidazole injection, inject able pantoprazole, intravenous fluid and one unit of blood transfusion. The patient was conservatively managed for acute pancreatitis and nasogastric tube aspiration and nil orally for 5 days. The patient recovered within a span of 7 days after which the MP was negative. Serum amylase, serum lipase, Urea, Creatinine and bilirubin came down to 100IU/L, 230 IU/L, 28mg %, 0.8 mg%, 4.2 mg% respectively on 7th day. Repeat USG of abdomen revealed only mild hepatomegaly. The patients was relieved on 14th day of admission.

DISCUSSION:
Pancreatitis clinically presents with upper abdominal pain accompanied by elevated levels of pancreatic enzymes i.e amylase and lipase. The type such as acute chronic haemorrhagic, necrotic are distinguished by history, clinical , biochemical and radiological findings.

Acute pancreatitis presents as neusea, vomiting , anorexia, abdominal pain. Out of numerous causes of acute pancreatitis malaria is rare. But it must be looked for in tropical country like India with high prevalence of malaria.

Falciparum malaria is the deadest among all other types of malaria with varied complications, multiorgan involvement and diverse sequlae. The parasite may affect pancrease causing acute pancreatitis or acute haemorrhagic pancreatitis. The clinical and laboratory findings follow similar pattern of other causes of acute pancreatitis.

The pathogenesis may be initiated by sequestration of parasite in the organ, blood vessels or ducts, damaging acinar cells by premature activation of digestive enzymes with cells. The damaged acinar cells initiate inflammation, activation of platelets and compliment system, which leads to release to cytokines (e.g TNF - , IL � 1, NO, PAF), free radicals and other vasoactive substances. These further directly damage the gland and may cause pancreatic oedema, necrosis, ischaemia and capillary leak syndrome. Tehse lead to a vicious inflammatory cycle damaging further pancreatic tissue. Association of sepsis further leads to organ damage and complications.

Malaria presenting with classical symptoms and signs of acute pancratitis along with other organ involvement may be difficult to correlate. The abdominal pain may be sharp, sudden or constant may be localized to epigastric,periumbilical, block or lower chest. But common presentation in malaria is fever, icterus with distended abdomen, diffuse or localized tenderness. Grey Turners signs or Cullen sign may be noted in advanced cases.

Blood count and chemistry panel usually distinguishes pancreatitis from other acute abdominal causes, Test of malaria (MP, Slide , QBC, ICT) determines malaria aetiology, Increased TLC, Hyperglycaemia, decreased Ca++, Increased alkaline phsophatase, S. Amylase, S. Lipase reflects pancreatic damage.

Serum amylase has low sensitivity (75-92%)and Specificity (20-60%) but is used to confirm acute pancreatitis , when upper limit is raised 3-6 times of normal specificity increases. Serum amylase level is raised 2-12 hours after pancreatic insult and peaks 12-71 hours after.

Serum lipase having sensitivity 86-100% and specificity of 50-99%. Serum lipase raised 4-8 hours after signs and symptoms and peaks at 24 hour and decrease over 8-14 days.

Other recent markers are immunoreactive cationic trypsin, pancreatic elastase � 1 and phospholipase.

Although USG and Ct scan of abdomen makes the diagnosis easy, cholangio-pancreatography may be accompolished bu ERCP or MRCP.

The primary treatment of acute pancreatitis with malaria is to treat the cause i.,e malaria. The treatment of acute pancreatitis is primarily supportive providing adequate hydration, pain relief and pancreatic rest by nasogastric suction and nil orally. Antibiotics are added to prevent sepsis or necrotic pancreatitis with setting of multiorgan involvement.

The prognosis of acute pancreatitis with malaria depends on the stage of presentation, haemorrhagic pancreatitis bears poor prognosis.

CONCLUSION
Falciparum malaria which has various complications may present as an acute pancreatitis, along with other organ affection. This is a rare condition and must be in mind of clinicians when patient presenting with clinical features of malaria, with pain abdomen , vomiting and localized abdominal tenderness.

A high index of suspicion and thorough clinical examination and investigation are the ways to diagnose the complication i.e, acute pancreatitis. Specific antimalarial drugs are the primary modalities of treatment, along with the conservative management for acute pancreatitis.

REFERENCE:
1. Von Sonnenberg F, Los Cher T, Nothdurgt HD, Prufer L @ Pubmed . PMID : 3519146.
2. Michelle M, Piet Zak MD (1) Dan W Thomas MD (2).
3. Parenti DM, Steingberg W, Kang P � Infectious causes of ac pancreatitis , 1996; 13(4) � 356-71.

INTRODUCTION
Sickle cell disease is an autosomal dominant disorder, sickle haemiglobin is the abnormal haemoglobin  chain glutamin acid is replaced by valine. Sickle haemoglobin has the unique property of forming polymersdeoxygenated state. These polymers deform the RBCS to sickle cell. Formation of polymers depends on the concentration of HbS inside the cell. So small reductions in HbS concentration inside the cell might result in significant clinical benefits. That is the reason why sickle cell trait is clinically silent were the HbS concentration is low. With better understanding of pathophysiology of sickle cell disease and its complications, it treatment has also progressed.

Among the haemolytic anaemias, vasoocclusive features are unique in SCD. Now it is well understood that vasoocclusion and tissue ischaemia in SCD involve not only the polymerization of HbS but also interaction between RBCs, endothelium, leucocytes, platelets and plasma factors. Intracellular polymerization of HbS is decreased by a rise in foetal haemoglobin and there increasing HbF is the most clinically studied approach against sickling. Infections, brain injury, renal disease , pain priapism can now be prevented. Complications from lung injury, surgery and transfusion can be minimized.

Management of SCD
Apart from general measures and treatment for symptomatic relief , now the newer therapeutic agents are directed towards prevent of complications.

THERAPEUTIC STRATEGIES FOR PREVENTION OF COMPLICATIONS
Sickling can be interrupted at several key pathways:
1. HbF Augmentation
Most promising agent in hydroxyurea, a ribonucleotide reductase inhibitor, causes myelosuppressive � induced HbF synthesis, resulting in improved red cell survival and decreased sickling. Hydroxyurea is orally active, effective , safe in short term and beneficial in most patients, in the dose of 10-15mg/kg to a maximum of 35 mg/kg. Before starting hydroxyurea, base line evaluation like blood counts, MCV, HbF concentration and serum chemical values and test for pregnancy ( a contraindication) to be done. Blood counts should be performed every 4-6 weeks intervals, granulocyte count should be at least 2000/mm3 and platelet counts at least 80,000/mm3 before or during treatment. An initial Hb concentration below 5.5 gm% is not a contraindication to treatment with hydroxyurea. Adults with higher TLC and reticulocyte counts and larger treatment associated decreases in these counts tends to have greater increases in HbF production and hence better response to hydroxyurea. Although hydroxyurea lowers pain episodes, pulmonary events and hospitalizations, 40% of treated patients do not respond or have progressive organ failure, the reason for this is yet to be settled.
Clinical advances in treatment of SCD
Clinical Features Interventions
1. Pain � Prevention with hydroxyurea
� Patients controlled analgesic devices
� Newer NSAIDS
2. Infection vaccine � Prophylactic penicillin and pneumococcal
3. Anaemia � Phenotypically matched RBCs
4. Lung injury prevention � Hydroxyurea
� Antibiotics (Macrolides)
� Transfusions
� Screening for pulmonary hypertension
5. Brain Injury prevention � Screening with transcranial Doppler , MRI, neurocognitive testing
6. Renal � ACE inhibitors for preteinuria
� Improved renal transplantation
7. Call bladder disease � Laparoscopic cholecystectomy
8. Surgery / anaesthesia safety � Preoperative transfusion
9. Priapism � Adrenergic agonist
� Antiandrogen therapy
10. Avascular necrosis of hip � Decompression coring procedures
11. Severe disease (recurrent acute chest syndrome, pain crises or CNS disease) � Allogenic BMT (< 16 years)
� Chronic transfusion and /or hydroxyurea
12. Neonatal screening
13. Family counseling


Other drugs which can increase HBF concentration are short chain fatty acids like valproic acid, 2-deoxy- 5 azacytidine , erythropoitein.

Other emerging therapeutic agents
Drug Mechanism Benefits
1. Clotrimazole Inhibits red cell Gardos channel Red-cell rehydration
2. Sulphasalazine Endothelial Activation Antiadhesion therapy
3. Deferiprone Chelete membrane iron Antiadhesion therapy
4. Acenocumarol, heparin Decrease thrombin Antiadhesion therapy
5. Pheresis Decrease HbS Transfusion therapy
6. Allogenic � Haematopoietic stem cell transplantation
7. Genetherapy �
a. Direct gene replacement � Direct delivery of &#61538;- globin gene.
b. Indirect gene therapy � Srythropoitin delivery

2. Antisickling agent (through multiple pathway)
Nitric oxide (NO) is a critical factor in the pathphysiology of SCD and hence a potential treatment option. NO regulates vessel tone , endothelial adhesion, leucocytes and platelet activity, an important factor in ischaemia reperfusion injury and sickle cell induced ischaemia. In SCD, more adhesion molecules are produced due to decreased availability of NO. Oral arginine supplementation induces NO production, reduces red cell sickling by inhibiting the Gardos channel (Calcium activiated K = Channel). Treatment of sickle � cell patients with NO or its precursor L arginine have shown promising antisickling activity with vasodilator properties. NO or arginine supplementation may be synergistic with hydroxyurea and seems to further increase. No release and decrease adhesive molecules.

CONCLUSION:
The need to study new applications of current treatment and to devise new treatments direct at disrupting multiple factors of the pathophysiology of the disease remains most important. New therapeutic options like hydroxyurea. No or L-Arginine, BMT, gene therapy appears promising. While awaiting the new treatments for the underlying disease, several partial problems remains unsolved. For example, how should the acute chest syndrome be managed, which patients should undergo exchange transfusion? How aggressively should be blood pressure be lower to decrease the risk of stroke? Can we better understand the cause of striking variability in sickle cell disease, so that hazardous treatment can be directed to the patients who are most likely to have the worst disease complications?

REFERENCES:
1. Bunn H.F. Pathogenesis and treatment of sickle cell disease. N. Engl J Med 1997; 337:762-9.
2. Steinberg M.H. Management of sickle cell disease. N. Engl j Med 1999;340:1021 � 30.
3. Morris C.R., Kuypers A., Larkin S et al : Arginine therapy : a novel strategy to induce nitric oxide production in sickle cell disease. Br J Haematol 2000; 111-498-500.
4. Vichinsky E . New therapies in sickle cell disease. Lancet 2002; 360: 629-31.

ABSTRACT:
We report a relatively uncommon association of massive pleural effusion (left) with pancreatic pseudocyst in an adult male patient. The pathophysiology, clinical features diagnosis and management of this conditions are reviewed. (The Ind. Pract 2004; 57(8): 553-554).

Key Words: Pancreatic Pseudocyst, Pleural Effusion

INTRODUCTION
Pseudocysta are localized collections of panecreatic secretions that lack and epithelial lining and persist for more than 4 weeks. In the past pseudocysts were detected. indirectly by clinical suspicion, appearance of a palpable abdominal mass and from barium contrast studies that demonstrated a mass. The advent of pancreatic imaging by ultrasonography and CT Scan has lead to the realization that pseudocysts appear in 10% patients with acute pancreatitis.

A variety of clinical and radiographic finding have been associated wit pancreatitis and pleural effusion is one of them. pleural effusion may be bilateral, confined to left side or rarely right sided and may be massive.

CASE REPORT
A 50 year old male patient admitted with history of chest pain for 1 month, swelling of abdmen with upper abdominal pain for 1 month, loss of appetite with nausea for 15 days and dyspnoea for last 3 days. Six months prior to admission he was provisionally diagnosed to be a case of pulomonary tuberculosis with left sided pleural effusion and was on treatment with ATT (4 drugs) for 6 months without any clinical improvement. He is not a known case of DM, HTN, SCD. No history of intake of other drugs. He is a chronic alcoholic for last 20 years.

On examination the patients was of average built with mild pallor, no icterus, no lymphadenopathy, with a pulse rate of 76 per minute, regular BP=118/80 mmHg. Cardiavascular system examination revealed apex beat Rt. 5th ICS. Chest examination revealed trachea shifted to right side. on left side reduced movement , stony dull percussion note, vocal response absent, breath sound diminished. Per abdomen examination revealed mild hepatomegaly with a firm intra abdominal swelling palpable in the middle left upper abdominal region, non tender with irregular margin.

INVESTIGATIONS
Hb = 8.6gm%
TLC = 8000/mm3
DC =N-60% , E-4%, L-36%
ESR =25mm 1st hr
FBS = 92mg%
Urine =NAD
S. urea = 38mg%
S. Creatinine = 1.1 mg%
Na+ = 135m.mol/L
K+ = 3.4 m.mol/L

Pleural fluid analysis revealed , coffee coloured, haemorrhage fluid with TLC could 700 mm3 mostly mestothelial cells mixed with cellular elements of blood. No malignant cells seen. Biochemical study revealed glucose- 60mg% protein � 1.6mg%. LDH- 2280IU/L Amylase- 30 IU/L.

Chest X- ray (PA view0 reveals massive pleural effusion (lt) with trachea shifted to rt.side. USG abdomen and pelvis reveals head of pancreas normally seen but the body and tail could not be visualized. A large cystic lesion of 15cm x 12cm with echogenicity seen with left sided pleural effusion.

The patient was diagnosed as a case of pancreatic pseudocyst with left sided pleural effusion due to acute pancreatitis probably alcohol induced. Pleural tapping was done and about 3000ml of haemorrhagic fluid was drawn out. He was put on of loxacin. valdecoxib, haematinics and other supportive treatment. The patient showed marked improvement during hospital stay and planned for surgical management for the existing pseudocyst.


DISCUSSION

Pancreatic pseudysts are collections of tissues, fluid debris enzymes and blood which develop over a period of 4 weeks after the onset of acute pancreatitis and constitute about 10% of patients of acute pancreatitis. It is encountered most frequently with alcoholic panaceatitis. Pseudocysts associated with pleural effusion are most common on the left but may be bilateral and rarely limited to right pleural space (Gumaste Singh, Dave et a, 1992) it is assumed to be a new prognotic parameters for acute pancreatitis (Lankisch Droge, Becher et al1994).

Psyeuodycysts lack epithelial lining and disruption of the pancreatic ductal system is common. Approximatelty 85% are located in the body or tail of pancreas and 15% in the head. If the pancreatic duct disruption is posterior, an internal fistula may be develop between the pancreatic duct and the pleural space producing a pleural effusion which is usually left sided and often massive. Conservative therapy is indicated if the pseudocyst is shrinking evidenced by serial ultrasound and minimal symptoms pseudocysts (every 3 to 6 months) Long acting somatostatin anagogic octreotide which inhibits pancreatic secretion is useful in cases of pancreatic ascetics with pleural effusion.

Pseudocyst with communicating duct if strictured require internal surgical or endoscopic drainage. Transgastric percutaneous approach is favoured. Associated massive left sided pleural effusion often required thoracentesis or chest tube drainage. A disrupted pancreatic duct can be treated by stenting.

CONCLUSION

Association of the left sided massive pleural effusion with pancreatic pseudocyst is relatively uncommon. However, additional studies are needed to substantiate these results.

REFERENCES
1. Gumaste V., Singh, V., Dave P. Significance of pleural effusion in patients with acute pancreatitis. Am J. Gastroenterilogy 1992; 87: 871.
2. Lankisch P.,G. Droge M and Becher R. Pleural effusion : A new negative prognostic parameter for acute pancreatitis. Am J Gateroesterol 1994; 89: 1849.
3. Slesinger and Fordtran�s Gastrointestinal and liver disease (6th edn) vol1 Sleisenger Feldman Scharshmidt Klein (W.B Saunders Co) 815:826:836.
4. TB of Gastroenterology (Vol-II) 2nd Edn Year 1995 (T. Yamada. J.B. Lippincott Co. Philadelphia ) page 2078-84.
5. Harrisons principles of Int. Medicine 15th Edn Vol 2 year 2001: Page-1798.

INTRODUCTION
The Indian subcontinent is home to more than 230 species of snakes of which some are poisonous. In 4 families of venomous snakes, 6 species are responsible for snakebites & are medically important in India.
They are :-
1.Elapidae. Represented by * Cobras a. King Cobra (Ophiphagushannah)
b. Common Cobra (Naja Naja)
* Krait. (Bungarus ceruleus)
2. Hydrophilidae - Seasnakes.
3. Viperidae - Russel viper/Saw scaled vipers.
4. Atractasipidae.
Here the epidemiology, pathogenesis, clinical features and managements are discussed.
EPIDEMIOLOGY
It is widely agreed that India contributes the largest share to the annual worldwide mortality due to snake bite. Figures of mortality range from 15000,to 40,000/year in India. Hospital records the sole source of most snakebite likely to over represent the more seriously envenomed patients. As in developing countries like India 80% of victims first consult traditional healers, so population survey gives most accurate picture of diagnosis than hospital record. First of all it was SWAROOP STUDY which reported about 200,000 bites/yr and 15,000 deaths as far as back in 1954. based on epidemiologic survey of 26 villages with a total population of 19,000 in Burdwan Dist. of W.B. HARI et all worked out an annual incidence of 0.16% and mortality of 0.061%. Myanmar has the highest snake bite mortality in the world. Maharastra has highest incidence of snakebites i.e 70bites per 100,000 population/year, with mortality of 2.4/ 100,000 per year. Bengal, Tamilnadu , UP & Kerala, are other states with large no of snake bites. Chippaux study shows marked increased frequency of - illegitimate bite in Developed countries and hazardous bite in developing countries.

Age & Sex
Though all age groups of both sexes are the victims majority are 11-50 years of male suggesting special risk in outdoor activities. Males are victimized twice or thrice than females.

Time & Seasonal variation:-
Maximum incidence between 4.00pm to midnight (varies with outdoor activities). During rainfall & epidemics after floods and natural disaster.
Site of bite:-
Most frequent site of bite � Lowerlimb(2/3rd ) of which 50% occur in feet alone.
Host factors:-
Occupational hazards- for farmers, harder, hunter & fisherman.
Morbidity & mortality:-
Depends upon the species of snake involved as estimated fatal dose of the venom varies with species.
Average Yield/bite Fataldose is much smaller
1.Cobra - 60mg 12mg.
2.Russelviper � 63mg 15mg.
3. Krait � 20mg 6 mg.
4. Saw scaled viper � 13 mg 8 mg.
Severity of Envenoming:-
Depends upon the dose of venom injected, composition & potency of venom, number & depth of bites, age of the victim, site of bite, nature, timing & quality of first aid & medical treatment.

PATHOPHYSIOLOGY OF OPHITOXEMIA:-
Most complex of all poisons are mixture of enzymatic & nonenzymatic compound, nontoxic proteins including carbohydrates & metals.
Enzymes � It is a constitute of 20 different enzymes including phospholipase. A2 B, C, D, hydrolases, phosphatases, proteases, esterase, Acetyl choline esterase, transaminase, hyaluronidase, phosphodiesterase DNAse RNAse etc.

Nonenzymatic compounds are - Neurotoxins
- Haemorrhagins.
Different species have different proportion of most of it. So they are formerly categorized as neurotoxic, haemotoxic, myotoxic but strict categorization is not essential
� Neurotoxins
Cobra � Cobrotoxin & bungarotoxin causes postsynaptic blokage (at moter end plate release of Ach).
Krait � B bungarotoxin causes pre synaptic blockage
Viper � Acetylcholine esterase causes breaksdown of Ach.
� Cardiotoxins
Cobra & Taipan � cardiotoxins causes myocardial depression and cardiac arrythmias.
� Vasculotoxins
Viper � Viper venom � affects coagulation pathways at several points. Activates factors V, IX, X, XII, platelets & protein C & fibrinolysins.
Haemorrahgins � damages endothelium to produce spontaneous bleeding, potentiates platelet aggregation & favours vasodilation.
� Myotoxins
Sea snake - Myotoxins produces muscle necrosis, myoglobinuria, hyperkalaemia.
� Nephrotoxins
Vipers � Indirectly damage renal system and causes prolonged hypotension, hypovolumia and hyperkalaemia/DIC/direct damage/rhabdomyolysis.
� Locally affecting toxins are protease, phoshpolipase 2, polypeptide toxins, hyaluronidase, histamine/brady kinin, hydrolanse
� Proteolysis
(Damages RBC, leucocytes & platelet membranes & vascular endothelium & other membranes.)

Increase Vascular permeability � Local effects, (swelling, edema inflammation, gangrene).

Systemic effects.

(Hypoalbuminemia) (hypotension) (shock)
CLINICAL FEATURES
I. Snake bites with no manifestations:
Confirmed bites with no manifestations � Drybites by poisonous snakes and bite by non poisonous snakes, Large no of studies show that a lot of poisonous bites do not cause symptoms, Banerjee � noted 80% of victims have no evidence of envenomations. Reid also states that over 50% of individual bitten by poisonous snakes escape with hardly any feature of poisoning, Stainly�s 117 out of 200 cases showed envenomation, Lamb states that 30% of cobra bites are superficial.

II. Local manifestations :-
Physiological trauma is the earliest. Local reactions are marked in both families of elapidae and viperadae ( krait is the exception). Local reactions are noted within 6-8 mins but may have onset upto 30min & develop upto 24 hrs. Local pain , with radiation & tenderness and the development of small reddish wheal are first to occur followed by oedema, swelling & appearance of bullae progressing rapidly involving trunk. Tingling, numbness over tongue, parasthesia around wound local bleeding including petechial & purpuric rash � more common in viperbites. Regional lymphadenopathy is an early & reliable sign. Intercompartmental syndrome- occur in 10% of cases. Necrosis of skin, subcutaneous tissue & muscle causes increased intercompartmental pressure which leads to pain & anasthesia on stretching of intercompartmental muscles. Severe pain, absence of arterial pulses and cold segment of limbs is due to thrombosis of major arteries which may lead to dry gangrene. All the above features of local reactions are evident in elapidae but the gangrene is mostly wet gangrene. In rare instances patients may have � Raynaud�s phenomenon/ secondary infection/ tetanus/ gas gangrene.
III. Systemic Menisfestations:
The most common and earliest symptom following snake bite is fright of unpleasant & rapid death. Victim attempts flight which unfortunately results in enhanced systematic absorption of venom leading to psychological shock & even death . Fear may cause transient pallor, sweating & vomiting.
Time of onset of systemic poisoning in cobra � 5 min to 10 hrs, Viper � 20 min to several hrs and Sea snake � almost always within 2 hrs.
Systemic manifestations depend predominantly on the constituents of the venom of that particular species as neurotoxin (cobras & kraits) haemorrhagin(vipers) myotoxin(sea snake), but strict categorization is not valid.
a) Neurotoxic features
Usually within 6 hrs but may be delayed. Symptoms are usually preceded by preparalytic syndromes which includes vomiting, blurred vision, drowsiness , heaviness of head, tingling sensation of mouth. Paralysis first appears as bilateral ptosis followed by bilateral opthalmoplegia, followed by paralysis of muscles of palate jaw, tongue , larynx , neck & muscles of deglutition . Muscles innervated by cranial nerves are involved earlier. Pupils react to light till terminal stage. Reflexes are not affected usually & preserved till late stages. Muscles of diaphragm are involves late which accounts for terminal respiratory paralysis. Onset of coma is variable ( may progress to coma in 2hrs).

b) Cardiotoxic features:-
Include tachycardia, hypotension, & ECG changes. 25% of viperbite include rate/rhythm/bloodpressure fluctuation. Sudden cardiac arrests may occur due to dyselectrolytemia. Though nondyselectrolytemia MI has also been seen.
c) Haemostatic abnormalities:-
One case of nonbacterial thrombotic endocarditis-reported from, PGI Chandigarh. Bleeding from the punctured wound is the earliest feature, Blood do not coagulate due to consumption coagulopathy &haemorrhagins produce widespread bleeding detected as bleeding gum, nose, GIT (haematemesis & melaena), Urinary bladder (haematuria). Consequent to bleeding hypotension & shock occurs. Intracerebral haemorrhage may occur. Subarachnoid haemorrhage is reported in 5 in 200 cases of Saini�s series in Jammu,(most were elderly).
d) Nephrotoxicity:-
In a series of study of Clarke out of 40 viper bites renal failure was detected in 3. The extent of renal abnormalities is correlated with the amount of coagulation defect . However renal defect persisted for several days after coagulation defect normalized, suggesting that multiple factors are involved in venom induced ARF.
e) Hypotension syndromes :-
Due to increased capillary permeability � menifested by serous effusions/ pulmonary edema/ haemoconcentration/hypoalbuminemia/shock.
f) Pregnency outcomes:-
Almost all pregnant abort or present with APH/PPH.
g) Rare outcomes-
Hypopitutarism, bilateral thalamichaematoma, hysteric paralysis.
LABORATORY DIAGNOSIS:-
� History- Patient usually gives history of snakebite but it may be absent in kraitbite (painless). Although fangmarks are essential fatal envenoming do occur without identifiable marks.
� Cell counts � Neutrophillic Leucolytosis
- Anaemia
- Thrombocytopenia
- Haematocrit � Initially ( haemoconcentration), Later ( haemolysis).
� Coagulation profile - Prolonged clotting time
- Prolonged prothrombin time.
- Fibrin Degradation products ( >80 mg/dl).

� Simple bedside test
(1) Tourniquet test � Torniquet pressure of 100 � 120 mm of Hg is applied for 5 minutes � (+ve) if >5purpuric spots.
(2) Whole blood clotting test :- 5ml of blood taken in clean, dry test tube- undisturbed for 20 min � seen for clotting.
(3) Clot quality observation test (Clot retraction test):- seen for clotting after one hour

� Urine Analysis
All snake bite patients should be advised to evacuate bladder at first aid & urine examined for microscopic haematuria. It could also reveal proteinuria, haemoglobinuria or myoglobinuria.
� Features of Azotemia S.Urea , S.creatinire may be raised.
� Metabolic parameters:- Hyperkalaemia, Hypoxemia, Respiratory acidosis may occur
� Myotoxicity is evidenced by � Raised Sr.CPK, & transaminase .
� ECG shows � Nonspecific alteration in rate, rhythm, predominently bradycardia, menifestation of hyperkalemia.
� X-ray chest � To rule out pulmonary edema/Infarction/bronchopneumonia/pleural effusion
� CT scan - May be required if suspision of Intracerebral bleeding,
� Immunodiagnosis

Detection of venom antigens in bodyfluids �
Used for - Pathophysiology
- Assessment of first aid
- Antivenom dose monitoring.
ELISA test � (venom detection kits) - Highly sensitive but not specific.


MANAGEMENT
1. First aid:-
Reassurance (to flight & fright response), Immobilisation of bitten limb, No tampering of the wound is best (Reid). Aim should be to transfer the patient to nearest hospital as quickly as passively as comfortably as possible.

Controversial first aid methods which are :-
� Local incision, excision of bitten skin , cauterization, amputation of digits
It has been proved from animal studies that all these methods do not decrease systemic envenomation, rather potentates bleeding introduces infection damage tissues.
� Suction by mouth as shown in Indian cinema has been rejected by its questionable efficacy while some advocate large amount of venom can be aspirated by this method if approached within seconds.
� Introduction of chemicals are worthless ( Nowhere recommended in any textbooks& therapeutics, rather rejected by Mansoon)

2. Use of tourniquets, compressionpads, bandages (controversial):-
Manson � Tight tourniquets have been responsible for terrible morbidity & mortality in snake bite victims & should not be used .
Sautherland (Australia)- advocated a pressure immobilization method by crepe bandaging proved effective in limiting absorption of venom ( applies p.of 55of hg). It is just tightly as sprained ankle starting from toes & fingers & incorporating a splint. It should be binded so tightly that only lymphatic circulation is obliterated not arterial. One finger should be introducible between the affected part & tourniquet. Use of tourniquets may be dangerous as they can cause gangrene, fibrinolysis, bleeding from occluded limbs, peripheral nerve palsy, compartmental ischaemia , intensification of local reaction. So general consensus in Western countries is to use crepebandage & splints in Elapidae and Sea snakes bites and to be avoided in Viperbites, which are responsible of intense local reactions. Clinical trials are needed to prove the efficacy of tourniquets & Compression bandage. The patient should be transferred in Lt. Lateral decubitus position to prevent aspiration.
3. Drugs :-
Reid advocated pain relief with placebo was as effective as NSAIDS. Gellert- experienced that codeine sulfate should be given to calm the patient & to reduce autonomic hyperactivity. Vomiting � can be treated with chlorphromazine ( 25-50mg IV infusion.) Others symptoms like syncope , shock, angioedema if supervene 0.1% adrenaline S/C can be given as first aid .


4. Specific Therapy :-
A. ANTIVENOM :-
Decision � In the management of snakebite, the most important clinical decision is whether to give antivenom therapy. For only a minority of snakebite patient need it. It may produce severe reactions & it is expensive & often in short supply.
Preparation:- They are prepared by immunizing horses with venom of poisonous snakes & extracting serum & purifying it . They may be species specific monovalent form/ poly valent form . Supplied as dry powder & reconstituted with DW or NS.
INDIA � C.R.I. Kasaulli � Antivenom against 4 medically important species are available.
Hopkins institute Pune � Against 30 species are available.

INDICATIONS OF ANTIVENOM TREATMENTS
a) Systemic envenoming
Neurotoxicity (ptosis, opthalmoplegia), incoagulable blood indicating consumption coagulopathy / DIC, spontaneous systemic bleeding ( from gingival sulci , nose), hypotension ( shock), generalised rhabdomyolysis. ( stiff tender painful muscles darkurine, myoglobinuria), impaired consciousness.
b) Severe local envenoming
Extensive local swelling ( > � of bitten limb), rapidly evolving local swelling, bites on fingers and toes, wider range of indication are prescribed in wealthy countries.
Contraindications Atopic patients & those previously had reaction with equine antiserum.
Prediction of antivenom reaction :- Hypersensitivity testing by intradermal or S.C. injection of diluted antivenom have no predictive value for early and late antivenom reactions. However these tests delay the start of treatment & are not without risk.
Prevention of antivenom reactions:-
Desert et all advocated in their trial that significant reduction in ASV reactions (from 12.5 to 30%) if the patients are given adrenaline subcutaneously (0.1% of adrenaline).
It is a dictum that it is never too late to give antivenom as long as signs of venom persists (it can be given from 2 days of seasnake bite to many days after viperbite proved by Saini�s study) .

Average requirements of dose in various studies:-
1. Bhat(1974)[Jammu] Intermittent Bolus Dose
Initial � 20 ml
Repeat � 20 ml every 4to 6 hrs till clotting time (CT) normal Total Dose
80ml-in mild
100 ml � moderate
250 ml � severe.
2. Thomas & Jacob (1985) [Kerala] Continuous IV infusion 153 ml � Traditional
79 ml � modified
3. JIPMER (1994)
( Pondichery) Local envenomation :_
Systemic envenomation:-
Initial � mild to moderate
Severe defect �
Repeatdose - 50 ml Iv bolus (single)

100 ml
50-200ml
50 ml every 4 to 6 hrs till CT - normal
4. Tariang et al (1996)
( CMC Vellore)
High Dose ( 31 pts)
2 vials IV infusion over 2hrs followed by 2 vials over 4hrs 4hrly till CT becomes normal then 2vials infusion over 24hrs.
Total �89 ml Low Dose(29pts)
2vias over 1hr followed by 1vial every 4 hrly IV infusion over 24hr


Total � 47ml
5. Das et al (1999)
(JIPMER)
Despite of high dose 44.4% developed ARF and dialysis required. Total � 183.3ml(4patient)
70 ml - Bolus
30 ml over 6 hr/6hrly till CT becomes normal 153.8 ml(5pts)
30 ml bolus
30ml over 6 hr/6hrly till CT becomes normal

Suggestive tentative schedule:-
� Over various parts of the country recommended doses are:-
Viper � Initial dose � 20 to 100 ml
Repeat dose � 20 to 50 ml every (4-6) hr till CT is normal
Recurrence of coagulation defect � 20 to 50 ml.
Cobra/Krait � Initial dose � 200 ml preferred (100 ml effective)
Repeat dose � (50-100)ml 4 to 6 hrly - Until neurotropic sign disappear
King Cobra � (100-150) ml Monospecific ASV

Fab based Antivenom alt. to IgG

Dart et al 99 (1) It largely reduces the antivenom reaction
(2) Effectively reverses coagulation abnormalities.
However it requires repeated doses as � life is<12 hrs

Antivenom Reactions
Clinical features Treatment
1. Early anaphylactic reaction :-
(10 min �3 hrs) Itching, Utricaria, Vomiting, fever tachycardia
40% develop systemic hypotension bronchospasm, angioedema ( socarefull watch) -Adrenaline(0.5ml-1ml 1:1000/S.C)

Chlorpromazin 10 mg IV
(&#61613; Incidence with &#61613;dose incidence with refined antivenom and more in IM > Iv)
2. Pyrogenic reaction (1-2)hrs Fever, rigor vasodilatation Hypotension. Paracetamol(15 mg /kg)
3.Serum Sickness (7days )
(5-24 days) Fever itching arthralgia (TMJ) particular swelling mononeuritis plultiplex Albuminuria/ encephalopathy Chlorpromazin PM 2mg/4tim x5 days
Prednisolone
(5mg/4times x(5-7)days)

B. HYPOTENSION SHOCK � Fresh blood is ideal
- Ionotropic support
- I.V Hydrocortisone ( in delayed hypotension )
C. NEUROTOXICITY
� Bulbar, respiratory paralysis � cuffed endotracheal intubation / tracheostomy.
� Complete respiratory paralysis � Mechanical ventilation .
� Anticholine esterase � like Neostigmine produces a rapid useful improvement in neuromuscular transmission. Worth giving after Tensilion test
� Neostigmine � (50-100&#61549;g)/kg and atropine(0.06mg)4hrly or by continuous infusion .
D. RENAL FAILURE:
Cautious rehydration, Diureties if renal failure, Haemodialysis/ Peritoneal dialysis.
E. LOCAL INFECTION:
Tetanus toxoid, Antibiotics to prevent infection at the site of bite (chloramphenicol, erythromycin, penicillin) Bullae should be left as such, limb should not be elevated, Necrotic tissue debridgement should be done as soon as possible & denuded area should be covered with split skin graft.

F. INTERCOMPARTMENTAL SYNDROME:
Fasciotomy if I.C.P > 45mm Hg, Only after correction of coagulopathy
G. SNAKEVENOM OPTHALMIA:
Immediate wash with normal saline, Exclude corneal abrasion by slit lamp examination installation of local Antibiotic/Adrenalin to relieve pain.
H. HAEMOSTATIC DISTURBANCES:
After neutralising venom procoagulant by specific antivenom restoration of coagulability & platelet function may be achieved by giving fresh blood, fresh frozen plasma, cryoprecipitate or platelet concentrates. Heparin producing disastrous results must be avoided.
I. DRUGS:
Costicosteroids , Antitibrinolytics, Antihistaminics, trypsin and other herbal medicine have no proved efficacy rather harmful.
CLINICAL FOCUS
� As a tropical, agricultural and developing country snake bite is common in India . Few snakes are poisonous.
� Incidence is more is males with seasonal variation.
� The average yield/bite is much higher than fatal dose.
� Severity of envenoming depends on various factors.
� The venom is a complex combination of which neurotoxins haemorrhagin and myotoxins are lethal to human.
� The clinical presentation varies from local reaction (various grades) to variety of systemic manifestations.
� Diagnosis depends on history, simple bed side clot retraction test, urine analysis and other parameters depends on systemic involvement.
� Treatment protocol includes simple first aid, torniquet (controversial) symptomatic and specific antivenom (ASV) therapy.
� The antivenum has many reactions but still life saving. The dosage schedule varies in different studies and in different species of snakes.
REFERENCES
1. Mansons Textbook of Tropical diseases
2. Oxfont textbook of Medicine. Page 1; 925 � 1:935.
3. Harrisons principle of Internal medicine. Page 16th Edn 2593-2595.
4. API text book of medicine 2003, 7th Edition, 1279 � 1282.
5. www. pubmed. Com.
6. www.medfinder.com.
7. New England Jaurnal of Medicine.