sebum production and related disorders such as acne have long been thought to be under the control of systemic hormones . unexpectedly it has been found that intradermal injection of ct decreases sebum production . the ability to decrease sebum production allows for the treatment of a variety of new conditions that were not previously treatable with ct . moreover , without wishing to be bound by this theory , the mechanism by which ct decrease sebum production is by decreasing the release of the neuropeptide substance p . by “ clostridia neurotoxins ( ct )” it is meant the botulinum neurotoxin serotypes a - g produced by clostridia botulinum , beratii , and butyricum and tetanus toxin produced by clostridia tetani and other natural toxins with similar biologic effects , particularly the proteolytic effects on snare proteins . the scope of the invention is meant to include modifications where the modified ct or fragment thereof retains essentially similar biological action as the wild type ct . modifications include , without limitation : hybrid ct that combine heavy and light chains , or fragments of those chains , from different bt serotypes and tt . substitution of ct binding domain with , or the addition to the ct of binding domains from other bacterial toxins or viruses , ligands for cell membrane receptors , antibodies or antibody fragments , combine fragments of different ct either with each other or with binding and / or translocation domains of other bacterial toxins . substitution of the ct translocation domain , or addition to the ct of translocation sequences from other bacterial toxins , or chemically constructed translocation domains , or membrane transfer proteins such as the tat sequence . addition , substitution or subtraction of amino acids or chemical modification of amino acid side chains . recombinant forms of ct . delivery within the skin cells of nucleic acid coding for ct . by “ therapeutically effective amount ” it is meant of purposes of this invention that the ct is administered in a non - toxic amount sufficient to cause reduction in the occurrence or magnitude of the symptoms being targeted . at present ct is measured by biological assay ; a unit of bt is the amount that causes death to 50 % of mice when injected intraperitoneally . bt a is marketed as botox by allergan corp , irvine calif ., and as dysport by ipsen ltd , berks united kingdom . bt b is marketed as myobloc by elan pharmaceuticals , dublin , ireland . other bt serotypes are available from metabiologics , madison , wis . tt is not marketed for human use but is from list biological labs 7th floor , sea containers house , 20 upper ground , london se1 9jd , england . a therapeutically effective amount of ct will vary depending on : the area of skin to be treated as injections diffuse about 2 cm ; the method of application ; the serotype of toxin used ( approximately 20 - 40 bt - b units have the same effects as one bt - a unit in human clinical applications ); the exact preparation of the serotype ( potency of bt - a from the two commercial vendors varies . the same clinical effect requires 2 - 4 times the dose of dysport ( frpm ipsen ) than botox , the bt - a formulation , from allergan ). at present the use of bt - a for muscle indications varies from about 1 unit ( eye and larynx muscles ) to hundreds of units ( limb and major neck muscles ). the exact dosage will not require undo experimentation by those skilled in the art . ( saltzman m : drug delivery , ( 2001 ) oxford university press , new york , n . y ., transdermal drug delivery guy rh ( editor ) marcel dekker ; ( 2003 )). a detailed method of ct application to reduce sebum production will be disclosed and examples will be given to disclose minor variations for different specific conditions . sebum secretion was assayed by application of fine blotting paper to forehead skin . the skin area was first wiped with moist and dry cloths to remove any skin secretions . blotting at this time was negative . two sheets of blotting paper were placed on both sides of forehead and an elastic band was then placed around the forehead to gently press the blotting paper onto the skin . after 2 hours the blotting papers were removed , allowed to dry and then transilluminated . areas where sebum secretion occurred were significantly darker then the unstained areas . the pattern of non - injected forehead skin was the of a circular areas of approximately 0 . 25 to 0 . 5 cm in diameter that overlapped extensively resulting in an almost complete dark band 4 cm wide across the forehead . a 49 year old male was injected with 100 units of botulinum toxin b ( myobloc , elan , dublin ) the injection was made with a size 26 needle attached to a 1 cc syringe . the skin of the right forehead was cleaned with alcohol and the needle injection was placed into the center of the right forehead , equidistant from the eyebrow and hairline . the tip of the needle was advanced through the skin surface and injection was made intradermally . a white raised bleb approximately 0 . 5 cm in diameter was seen at the site of injection . directly after toxin injection , no change in blotting pattern was seen from uninjected patterns . one day after injection a repeat assay showed that a clear area was present at the site of injection with a diameter of approximately 1 cm . on the second day after injection the area had increased to a maximum of 1 . 5 cm . the cleared area gradually decreased in size and was not detectable at 2 months . in all trials the uninjected side did not show any clear areas . in another experiment on the same subject , 10 units of botulinum a ( botox ) at a dilution of 2 . 5 units per 0 . 1 cc of saline was injected intradermally into the mid forehead . after one day a clear area was found after blotting with a maximum diameter of approximately 2 . 5 cm . blotting showed a decrease in area by 50 % by 2 months and was not detectable at 4 months . one surprising observation was that the injected area became noticeably smoother within a few days after injection . this smooth appearance was due to smaller and less noticeable skin pores and a decrease in the fine wrinkling of the skin surface . both the flattening and smoothing effects lasted as long as the deceased sebum secretion and the skin texture returned to its former condition after the other effects also disappeared . this smoothing is distinct from the decrease in the larger skin wrinkles that occurs after facial skin is immobilized by botulinum toxin injection into facial muscles of expression . the etiology of these effects on skin texture are unknown . however , without wanting to be bound by theory it may be due to atrophy of skin glandular elements and associated tissue due to denervation by the botulinum toxin . the target glands are sebum glands of the face , shoulders and back . bt would be topically applied or injected so as to bind to the neurons stimulating the pilosebaceous glands and associated structures , thereby decreasing the production and / or accumulation of sebum . this could be done as treatment for exacerbations of the disease or as a preventive measure during quiescent periods . a patient with a long history of acne vulgaris presents with multiple comedones of both cheeks . five injections of 2 units of bt - a are injected intradermally into separate site of each cheek for a total of 20 units . a patient with seborrheic dermatitis presents with a widespread rash on her face and scalp associated with alopecia . twenty injections of 2 units of bt - a ( total of 40 units ) in injected into multiple sites involved in the disorder including the area of hair loss . a patient presents with a 1 centimeter mildly tender sebaceous cyst within the skin of the right inner thigh . a single injection of 5 units of bt - a is made into the cyst . a patient with chronic rosacea and rhinophyma presents for treatment . ten intradermal injections each containing 2 units of bt - a ( total 20 units ) are made at various places of the mid face , and five additional injections are made directly into the skin of the nose . a patient with chronic blepharitis of the eyelids of both eyes . the patient receives a single injection of 0 . 5 units of bt - a to the edge of each eyelid ( total 2 units ). a patient with a history of recurrent eyelid chalzions applies topical ointment containing 10 units of bt - a per cc is daily along with warm compresses . a patient has significant fine wrinkling of her facial skin that she feels is cosmetically objectionable . she undergoes topical application of 50 units of bt - a in a cream form to the skin of her forehead , periorbital region and cheeks . a patient has excessive sebum of the face requiring twice daily cleansing with special soaps that dry her skin . 10 injections , each of 100 units of bt - b are injected into the skin of the eyebrows , forehead , and nose and nasolabial folds . a female patient has post partum depression following a stillborn birth . to decrease the production of breast milk 3 injections of 20 units of bt - a are made into each breast ( 120 units total ). a female patient with perceived mammary hypertrophy learns she is pregnant . not wishing further enlargement of the breast during pregnancy she receives 3 injections of 20 units of bt - a are made into each breast ( 120 units total ). a patient perceives that the skin of her nose has large pores related to pilosebaceous glands . she is injected with two injections of 5 units of bt - a ( 10 units total ) to the skin overlying the nasal alae ) in one month the size of the skin pores has decreased by 50 %. a male patient experiences cerumen impaction every 6 months . each ear is injected with 5 units of bt - a into the skin at the junction of the bony and cartilaginous canals . abstracts of the international conference 2002 basic and therapeutic aspects of botulinum and tetanus toxins , hannover , germany , jun . 8 - 12 , 2002 braune c , erbugh f , birklein f : dose thresholds and duration of local anhidrotic effect of botulinum toxin injections measured by sudometry . br j dermatol ( 2001 ) 144 : 111 - 7 . chung c w , tigges m , stone r a . peptidergic innervation of the primate meibomian gland . invest opthalmol vis sci ( 1996 ) 37 ( 1 ): 238 - 45 . gibbins i l : target - related patterns of co - existence f neuropeptide y , vasoactive intestinal peptide , enkephalin and substance p in cranial parasympathetic neurons innervating the facial skin and exocrine glands of guinea - 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( 2001 ) j comp neurol 432 ( 4 ): 466 - 80 . scott a b : botulinum toxin injection of eye muscles to correct strabismus . trans am opthal soc , ( 1981 ) 179 : 734 - 770 simons e , smith p g : sensory and autonomic innervation of the rat eyelid : neuronal origins and peptide phenotypes . j chem neuroanat ( 1994 ) 7 ( 1 ): 35 - 47 . thody a j , shuster s : control and function of sebaceous glands physiological reviews ( 1989 ) 69 : 2 , 383 - 416 toyoda m , morohashi m : pathogenesis of acne . med electron microsc ( 2001 ) march 34 : 29 - 40 villares j c : l - dopa , biperiden and sebum excretion in parkinson &# 39 ; s disease . arq neuropsiquatr 1989 47 : 131 - 8 . yosipovitch g . reis j , tur e , sprecher e , yarnitsky d , boner g . sweat secretion , stratum hydration , small nerve fuction and pruritus in patients with advanced chronic renal failure . br j dermatol 1995 133 ( 4 ) 561 - 4 us 1998 u . s . pat . no . 5 , 766 , 605 : treatment of autonomic dysfunction with botulinum toxin . wo03 / 011333a1 botulinum toxin in the treatment or prevention of acne
methods of using clostridial toxins and other biological agents to control holocrine gland dysfunction in humans is provided . in preferred embodiments the methods provide beneficial effects in humans .