1 00:00:05,490 --> 00:00:07,950 - This is Lab Medicine Rounds, a curated podcast 2 00:00:07,950 --> 00:00:11,310 for physicians, laboratory professionals and students. 3 00:00:11,310 --> 00:00:12,750 I'm your host, Justin Kreuter, 4 00:00:12,750 --> 00:00:14,640 a transfusion medicine pathologist 5 00:00:14,640 --> 00:00:16,890 and assistant professor of laboratory medicine 6 00:00:16,890 --> 00:00:18,810 and pathology at Mayo Clinic. 7 00:00:18,810 --> 00:00:20,250 Today we're rounding with Dr. 8 00:00:20,250 --> 00:00:24,030 Ashima Makol associate professor of Medicine, vice chair 9 00:00:24,030 --> 00:00:27,660 and practice Chair in the division of Rheumatology chair 10 00:00:27,660 --> 00:00:29,940 for the Connective Tissue Disease Group, 11 00:00:29,940 --> 00:00:34,080 and director for the scleroderma clinic here at Mayo Clinic 12 00:00:34,080 --> 00:00:35,580 in Rochester, Minnesota. 13 00:00:35,580 --> 00:00:37,770 Thanks for joining us Dr. Makol. 14 00:00:37,770 --> 00:00:40,200 - Thank you Dr. Kreuter for having me. 15 00:00:40,200 --> 00:00:42,665 - So I'm really excited to talk about this 16 00:00:42,665 --> 00:00:46,170 because this podcast episode is going live 17 00:00:46,170 --> 00:00:48,780 during scleroderma awareness month. 18 00:00:48,780 --> 00:00:50,790 And so I thought we could maybe kick it off 19 00:00:50,790 --> 00:00:54,635 with why is it important for healthcare professionals 20 00:00:54,635 --> 00:00:56,850 to be aware of scleroderma? 21 00:00:58,020 --> 00:00:59,340 - Yes, that's a great question. 22 00:00:59,340 --> 00:01:02,400 So we'll get started by really saying 23 00:01:02,400 --> 00:01:07,260 that scleroderma is a rare systemic inflammatory 24 00:01:07,260 --> 00:01:09,990 autoimmune disease, which I think is one 25 00:01:09,990 --> 00:01:14,520 of the most commonly undiagnosed, misdiagnosed, 26 00:01:14,520 --> 00:01:19,350 misunderstood, and mismanaged medical condition 27 00:01:19,350 --> 00:01:22,020 that as rheumatologists sometimes deal with. 28 00:01:22,920 --> 00:01:27,515 I think spreading the awareness about this rare condition is 29 00:01:27,515 --> 00:01:31,200 critical because it comes in many shapes 30 00:01:31,200 --> 00:01:35,820 and forms, it impacts kids and adults 31 00:01:35,820 --> 00:01:39,540 and it has one of the highest morbidity 32 00:01:39,540 --> 00:01:41,910 and mortality associated with some 33 00:01:41,910 --> 00:01:43,805 of our systemic rheumatic diseases. 34 00:01:43,805 --> 00:01:46,200 So early diagnosis, 35 00:01:46,200 --> 00:01:50,040 recognizing the internal organ involvement in some variants 36 00:01:50,040 --> 00:01:54,660 in particular Earth scleroderma, really helps get started 37 00:01:54,660 --> 00:01:56,940 with a good therapeutic plan 38 00:01:56,940 --> 00:01:59,730 and a prognostic understanding of what 39 00:01:59,730 --> 00:02:01,650 that particular patient is dealing with 40 00:02:01,650 --> 00:02:04,680 to optimize outcomes in the long run. 41 00:02:04,680 --> 00:02:07,500 - Wow. So you really kind of laid it on 42 00:02:08,430 --> 00:02:10,110 justifiably thick there. 43 00:02:10,110 --> 00:02:12,600 It's impressive. So it's a rare disease, 44 00:02:12,600 --> 00:02:16,980 but you really kind of hit on how such poor understanding 45 00:02:16,980 --> 00:02:21,060 of it and yet it has such significant consequences 46 00:02:21,060 --> 00:02:22,865 for the patient. 47 00:02:22,865 --> 00:02:24,540 So it's important, although it's, 48 00:02:24,540 --> 00:02:26,580 I suppose a rare disease, it's one 49 00:02:26,580 --> 00:02:28,380 that we should be thinking of and, 50 00:02:28,380 --> 00:02:32,070 and hence why this awareness month we're celebrating. 51 00:02:33,060 --> 00:02:34,685 You know, a portion of our, 52 00:02:34,685 --> 00:02:37,500 of our listeners are coming from a laboratory 53 00:02:37,500 --> 00:02:39,750 medicine background. 54 00:02:39,750 --> 00:02:42,360 I wonder if we could kind of dive into that a little bit 55 00:02:42,360 --> 00:02:45,000 and could you kind of elaborate on, you know, 56 00:02:45,000 --> 00:02:48,570 what are some important things for laboratory professionals 57 00:02:48,570 --> 00:02:51,360 to understand about scleroderma? 58 00:02:52,410 --> 00:02:56,370 - Yes, and one of the things I want to point out 59 00:02:56,370 --> 00:02:59,440 before we go into lab diagnosis is, as I mentioned, 60 00:02:59,440 --> 00:03:01,870 you know, scleroderma really is a broad term 61 00:03:01,870 --> 00:03:05,770 that encompasses a whole slew of different diseases. 62 00:03:05,770 --> 00:03:09,460 So while it can be something called localized scleroderma 63 00:03:09,460 --> 00:03:11,620 that can impact the skin 64 00:03:11,620 --> 00:03:13,210 and underlying tissues, 65 00:03:13,210 --> 00:03:17,440 mainly the subcutaneous tissue in a very patchy distribution 66 00:03:17,440 --> 00:03:20,050 that can be more systemic scleroderma, 67 00:03:20,050 --> 00:03:24,970 where it can be something that we call diffuse cutaneous 68 00:03:24,970 --> 00:03:28,725 or limited cutaneous and, and that limited 69 00:03:28,725 --> 00:03:31,210 and diffuse is really based on the extent 70 00:03:31,210 --> 00:03:32,980 of skin involvement. 71 00:03:32,980 --> 00:03:34,455 There are patients, however, 72 00:03:34,455 --> 00:03:37,665 who have very classic internal organ findings of 73 00:03:37,665 --> 00:03:40,870 what we call systemic sclerosis 74 00:03:40,870 --> 00:03:43,450 and they might have absolutely no skin involvement. 75 00:03:43,450 --> 00:03:45,670 And that's kind of confusing for a lot of people 76 00:03:45,670 --> 00:03:49,565 because the term scleroderma is derived from sclero 77 00:03:49,565 --> 00:03:53,470 and derma that literally means thick, hard, tight skin. 78 00:03:53,470 --> 00:03:56,980 And that's one of the hallmark features of the condition. 79 00:03:56,980 --> 00:04:00,010 Along with other features like raynaud's 80 00:04:00,010 --> 00:04:04,240 where fingers change colors in the cold become pale, 81 00:04:04,240 --> 00:04:07,180 dead white, purplish blue and red. 82 00:04:07,180 --> 00:04:12,180 But some of these symptoms can be present at the outset. 83 00:04:12,220 --> 00:04:13,900 They may develop over time. 84 00:04:13,900 --> 00:04:17,140 Sometimes the skin manifestations may never develop, 85 00:04:17,140 --> 00:04:20,590 while patients could have internal organ disease like 86 00:04:20,590 --> 00:04:22,185 pulmonary hypertension 87 00:04:22,185 --> 00:04:26,290 or GI dysmotility, they can have interstitial lung disease 88 00:04:26,290 --> 00:04:28,240 that might bring them to light. 89 00:04:28,240 --> 00:04:31,906 So it's a whole gamut of different subspecialty areas 90 00:04:31,906 --> 00:04:34,120 that these patients might really present in 91 00:04:34,120 --> 00:04:37,150 and undergo workup at. 92 00:04:37,150 --> 00:04:40,000 But lab medicine is very, very important 93 00:04:40,000 --> 00:04:42,070 and critical in the big picture 94 00:04:42,070 --> 00:04:44,385 because there are some classic blood markers 95 00:04:44,385 --> 00:04:45,460 that are associated 96 00:04:45,460 --> 00:04:48,700 with scleroderma also integrated into the classification 97 00:04:48,700 --> 00:04:51,820 criteria for systemic sclerosis, 98 00:04:51,820 --> 00:04:56,145 which are a positive ANA that can be seen in close 99 00:04:56,145 --> 00:04:58,660 to 90% plus patients. 100 00:04:58,660 --> 00:05:00,820 So that's a very good broad screening marker. 101 00:05:00,820 --> 00:05:03,820 And if you especially run into a centromere pattern 102 00:05:03,820 --> 00:05:07,780 or a nuclear or pattern that is highly predictive 103 00:05:07,780 --> 00:05:10,780 of a possible scleroderma spectrum condition in 104 00:05:10,780 --> 00:05:14,860 that patient, you can see more specific lab markers like the 105 00:05:14,860 --> 00:05:17,680 centromere antibody itself that is associated 106 00:05:17,680 --> 00:05:22,390 with the limited cutaneous phenotype that is the scl-70 107 00:05:22,390 --> 00:05:26,530 or the topoisomerase 1 antibody that is more associated 108 00:05:26,530 --> 00:05:29,560 with the diffuse cutaneous phenotype 109 00:05:29,560 --> 00:05:34,060 or development of interstitial lung disease 110 00:05:34,060 --> 00:05:35,500 and RNA polymerase III, 111 00:05:35,500 --> 00:05:37,750 which is a marker often people forget about. 112 00:05:37,750 --> 00:05:40,210 But that is also in the classification criteria 113 00:05:40,210 --> 00:05:44,320 and very strongly associated with a rapid skin progression. 114 00:05:44,320 --> 00:05:47,590 It is associated with scleroderma renal crisis 115 00:05:47,590 --> 00:05:51,970 and also a much higher risk of malignancy in one out 116 00:05:51,970 --> 00:05:55,090 of three individuals who carry that blood marker. 117 00:05:55,090 --> 00:05:58,850 So these patients really should be screened 118 00:05:58,850 --> 00:06:00,950 for these antibodies right at the outset, 119 00:06:00,950 --> 00:06:03,680 given the prognostic capability 120 00:06:03,680 --> 00:06:06,770 and a prediction of some of these internal organ 121 00:06:06,770 --> 00:06:10,100 or comorbid manifestations that can come along. 122 00:06:10,100 --> 00:06:13,430 But there are a whole host of rarer antibodies that 123 00:06:13,430 --> 00:06:16,850 that are out there as well that like the RNP 124 00:06:16,850 --> 00:06:19,310 or the fibrillin antibody 125 00:06:19,310 --> 00:06:22,340 that can also be seen in scleroderma patients, 126 00:06:22,340 --> 00:06:24,680 especially the systemic sclerosis. 127 00:06:25,850 --> 00:06:28,915 - Wow. So I mean this really highlights, you know, 128 00:06:28,915 --> 00:06:32,480 again your background as an internal medicine physician 129 00:06:32,480 --> 00:06:34,100 and as a rheumatologist 130 00:06:34,100 --> 00:06:39,100 because of all the different manifestations of this, 131 00:06:39,500 --> 00:06:41,815 why somebody with your background really needs 132 00:06:41,815 --> 00:06:43,940 to be involved with diagnosis and 133 00:06:43,940 --> 00:06:45,620 and treatment of these patients, 134 00:06:45,620 --> 00:06:48,470 I really appreciate you highlighting how is, 135 00:06:48,470 --> 00:06:49,495 if I'm hearing you right, 136 00:06:49,495 --> 00:06:53,690 like the laboratory testing can really help you, you know, 137 00:06:53,690 --> 00:06:57,500 rule in or or potentially rule out this rare diagnosis 138 00:06:57,500 --> 00:07:01,460 as well as it can help you understand 139 00:07:01,460 --> 00:07:04,880 where does it fit in within the scleroderma 140 00:07:04,880 --> 00:07:06,200 scleroderma spectrum. 141 00:07:06,200 --> 00:07:07,875 Did I understand that right? 142 00:07:07,875 --> 00:07:11,930 - Yeah. So lab testing I think is extremely helpful, 143 00:07:11,930 --> 00:07:13,640 but it is not everything. 144 00:07:13,640 --> 00:07:14,840 I think the clinical picture 145 00:07:14,840 --> 00:07:17,030 of a patient really trumps a lot of things. 146 00:07:17,030 --> 00:07:20,515 So there are patients who can have ANA negative scleroderma 147 00:07:20,515 --> 00:07:22,160 as I mentioned earlier. 148 00:07:22,160 --> 00:07:24,680 There are over 90% patients who are going to be 149 00:07:25,850 --> 00:07:29,720 having a positive ANA, but that is not universally true. 150 00:07:29,720 --> 00:07:33,740 There are patients with classic skin findings, 151 00:07:33,740 --> 00:07:38,355 interstitial lung disease raynaud's with digital ulcers, to 152 00:07:38,355 --> 00:07:40,400 langatasias, GI dysmotility. 153 00:07:41,420 --> 00:07:45,230 So the whole spectrum that diagnoses a patient 154 00:07:45,230 --> 00:07:48,170 with this particular disease entity, yet many 155 00:07:48,170 --> 00:07:52,855 of these may lack a autoimmune marker on their blood work. 156 00:07:52,855 --> 00:07:57,170 So seeing a rheumatologist is critical in the right setting. 157 00:07:57,170 --> 00:07:59,690 The faster we initiate that process, 158 00:07:59,690 --> 00:08:03,080 if we have suspicious symptoms, especially early on 159 00:08:03,080 --> 00:08:06,710 where there is tightening of skin involving the fingers 160 00:08:06,710 --> 00:08:10,700 or puffy fingers in particular, puffy more in comparison 161 00:08:10,700 --> 00:08:11,725 to their baseline 162 00:08:11,725 --> 00:08:13,340 and something that is more pervasive, 163 00:08:13,340 --> 00:08:16,940 not the fluctuate puffiness that we see, 164 00:08:16,940 --> 00:08:19,825 but that in combination with raynaud's in particular 165 00:08:19,825 --> 00:08:23,450 or joint pain in the hands should prompt people 166 00:08:23,450 --> 00:08:25,190 to think about scleroderma. 167 00:08:25,190 --> 00:08:27,320 - I think you just prompted all of our listeners 168 00:08:27,320 --> 00:08:31,520 to look down at their hands right now and check that out. 169 00:08:31,520 --> 00:08:34,520 I appreciate you kind of for the hypochondriacs among us, 170 00:08:34,520 --> 00:08:37,160 kind of allay our fears a little bit to kind 171 00:08:37,160 --> 00:08:38,660 of say you're talking about something 172 00:08:38,660 --> 00:08:41,715 that is pervasive if I'm understanding 173 00:08:41,715 --> 00:08:43,040 - That that is true. 174 00:08:43,040 --> 00:08:45,770 That is true, absolutely. So, 175 00:08:45,770 --> 00:08:47,750 - So as you talk through 176 00:08:47,750 --> 00:08:51,320 and talk about, you know, these lab tests are having value, 177 00:08:51,320 --> 00:08:52,675 but as you're pointing out it, 178 00:08:52,675 --> 00:08:55,500 it's really a full picture they contribute 179 00:08:55,500 --> 00:08:58,650 but it really also takes the astute physician 180 00:08:58,650 --> 00:09:02,310 that's als another group of our audience. 181 00:09:02,310 --> 00:09:04,895 If you were to, you know, highlight something 182 00:09:04,895 --> 00:09:07,680 for our clinician listeners 183 00:09:07,680 --> 00:09:11,460 or maybe something for our student listeners 184 00:09:11,460 --> 00:09:15,390 who are in training still in the health care professions, 185 00:09:15,390 --> 00:09:17,880 is there something you'd like to just kind of highlight 186 00:09:17,880 --> 00:09:20,160 or underline about scleroderma? 187 00:09:21,570 --> 00:09:25,890 - Yes. So scleroderma, as I mentioned, you know, many, 188 00:09:25,890 --> 00:09:27,990 many different ways it can present. 189 00:09:27,990 --> 00:09:32,990 But these are, you know, I would say 190 00:09:33,270 --> 00:09:35,760 one of the key things to keep in mind is 191 00:09:35,760 --> 00:09:40,760 what is highlighted in the ACR 2013 criteria 192 00:09:40,950 --> 00:09:44,225 and that is puffy fingers. 193 00:09:44,225 --> 00:09:49,225 You know, these puffy fingers are not your benign jargon. 194 00:09:49,440 --> 00:09:50,820 This is a medical jargon 195 00:09:50,820 --> 00:09:52,530 and that that's important to keep in mind. 196 00:09:52,530 --> 00:09:56,070 A pervasive puffiness of the fingers in combination 197 00:09:56,070 --> 00:09:59,640 with new onset raynaud's especially late in life 198 00:10:00,605 --> 00:10:02,160 after the age of 40, 199 00:10:02,160 --> 00:10:04,230 should definitely be taken very seriously. 200 00:10:04,230 --> 00:10:08,130 It might be the first sign towards a pointer 201 00:10:08,130 --> 00:10:10,620 that this might be a brewing autoimmune disease 202 00:10:10,620 --> 00:10:11,670 in that individual. 203 00:10:11,670 --> 00:10:14,580 Now you could also have other things like lupus 204 00:10:14,580 --> 00:10:17,435 or potentially mixed connective tissue disease in 205 00:10:17,435 --> 00:10:19,380 that spectrum of conditions as well. 206 00:10:19,380 --> 00:10:23,070 But I think it should put a plug in your mind about 207 00:10:23,070 --> 00:10:25,650 potentially looking for an ANA 208 00:10:25,650 --> 00:10:27,540 to start the screening process. 209 00:10:27,540 --> 00:10:32,105 And if you're highly suspicious about inflammatory arthritis 210 00:10:32,105 --> 00:10:36,300 or if the patient has GI symptoms of 211 00:10:36,300 --> 00:10:39,750 uncontrolled GERD that has been fairly longstanding 212 00:10:39,750 --> 00:10:43,830 and poorly managed, if there is difficulty breathing 213 00:10:43,830 --> 00:10:47,490 or concern about cardiopulmonary symptoms as well, 214 00:10:47,490 --> 00:10:49,926 getting them to the right subspecialty areas 215 00:10:49,926 --> 00:10:52,440 and starting off with a comprehensive rheumatology 216 00:10:52,440 --> 00:10:56,310 evaluation may be high yield. 217 00:10:56,310 --> 00:11:00,900 There is also certain basic physical examination maneuvers 218 00:11:00,900 --> 00:11:03,660 that I would like to highlight as a rheumatologist 219 00:11:03,660 --> 00:11:04,950 because this is not something 220 00:11:04,950 --> 00:11:08,490 that we were trained on very early in our med school 221 00:11:08,490 --> 00:11:10,145 or even internal medicine training. 222 00:11:10,145 --> 00:11:12,725 But we, we look at the skin and we look at the joints 223 00:11:12,725 --> 00:11:15,450 and sometimes we just ignore what 224 00:11:15,450 --> 00:11:17,940 our nail beds can demonstrate 225 00:11:17,940 --> 00:11:22,940 and give us a hyperview of in terms of the microcirculation. 226 00:11:23,250 --> 00:11:26,315 So there are some structural abnormalities 227 00:11:26,315 --> 00:11:28,710 of the microcirculation that we can look at 228 00:11:29,670 --> 00:11:31,650 in the nail nail folds 229 00:11:31,650 --> 00:11:34,170 of scleroderma patients in particular, 230 00:11:34,170 --> 00:11:37,860 or patients who have raynauds that starts late in life. 231 00:11:37,860 --> 00:11:41,100 And these may be another pointer towards the 232 00:11:41,100 --> 00:11:43,350 potential development of scleroderma 233 00:11:43,350 --> 00:11:45,150 where there are dilations 234 00:11:45,150 --> 00:11:48,450 or what we call giant capillary loops, micro hemorrhages. 235 00:11:48,450 --> 00:11:51,120 There is features of neovascularization 236 00:11:51,120 --> 00:11:53,800 and this can be seen simply within ophthalmoscope 237 00:11:53,800 --> 00:11:56,320 or a dermatoscope at the bedside at 238 00:11:56,320 --> 00:11:57,850 by looking at the nail beds. 239 00:11:57,850 --> 00:12:00,220 But we have more sophisticated ways of doing it 240 00:12:00,220 --> 00:12:02,530 with a nail fold video oscopy 241 00:12:02,530 --> 00:12:04,515 that is an advanced imaging procedure 242 00:12:04,515 --> 00:12:07,570 that magnifies the nail fold 200 times to get a better sense 243 00:12:07,570 --> 00:12:10,150 of what those structural changes look like 244 00:12:10,150 --> 00:12:12,550 and that are very classic findings of scleroderma 245 00:12:12,550 --> 00:12:15,490 that can be high yield in that situation. 246 00:12:15,490 --> 00:12:18,220 - Wow, that's fantastic. Thanks for highlighting that. 247 00:12:19,360 --> 00:12:22,120 I'm curious as you talk through, if I go to one 248 00:12:22,120 --> 00:12:23,200 of your earlier answers, 249 00:12:23,200 --> 00:12:25,990 you were talking about the different findings 250 00:12:25,990 --> 00:12:29,440 that we might find out, you know, with the ANA 251 00:12:29,440 --> 00:12:30,880 different patterns with antibodies. 252 00:12:30,880 --> 00:12:33,550 You said there was a whole host of, of other 253 00:12:34,570 --> 00:12:38,590 things in development as laboratory markers. 254 00:12:38,590 --> 00:12:42,340 Is, are the testing that might be done in support 255 00:12:42,340 --> 00:12:47,230 of a patient with scleroderma, is that strictly diagnostic 256 00:12:47,230 --> 00:12:49,540 or is there like a therapeutic 257 00:12:49,540 --> 00:12:52,300 or prognostic role as well? 258 00:12:53,230 --> 00:12:55,725 - So most of those lab markers are diagnostic 259 00:12:55,725 --> 00:12:57,490 and prognostic. 260 00:12:57,490 --> 00:13:00,910 They have certain key phenotypes associated with them. 261 00:13:00,910 --> 00:13:03,250 So one out of 10 people 262 00:13:03,250 --> 00:13:06,580 with a centromere antibody will develop pulmonary 263 00:13:06,580 --> 00:13:08,920 hypertension, which can be complicated 264 00:13:08,920 --> 00:13:11,650 by right heart failure and so forth in the long term. 265 00:13:11,650 --> 00:13:13,725 So that is definitely a reason 266 00:13:13,725 --> 00:13:17,020 to follow serial echocardiograms in these individuals 267 00:13:17,020 --> 00:13:18,670 or the individuals 268 00:13:18,670 --> 00:13:21,820 that have an RNA polymerase three antibody, 269 00:13:21,820 --> 00:13:24,250 we definitely re recommend 270 00:13:24,250 --> 00:13:26,650 that they buy a blood pressure meter 271 00:13:26,650 --> 00:13:29,890 and check their blood pressure periodically at home 272 00:13:29,890 --> 00:13:32,565 because a 20 point rise in their systolic 273 00:13:32,565 --> 00:13:36,160 or of sustained more than 10 point diastolic blood pressure 274 00:13:36,160 --> 00:13:37,815 elevation can be the first sign 275 00:13:37,815 --> 00:13:41,650 of potentially a scleroderma renal crisis where they can get 276 00:13:42,580 --> 00:13:45,580 renal dysfunction to the point of needing dialysis. 277 00:13:45,580 --> 00:13:47,110 And the sooner we can pick that up, 278 00:13:47,110 --> 00:13:49,870 the sooner we can start them on ACE inhibitors 279 00:13:49,870 --> 00:13:51,880 and get them into the hospital 280 00:13:51,880 --> 00:13:54,640 to control their blood pressure urgently, 281 00:13:54,640 --> 00:13:58,360 the better the long-term outcomes are in that individual. 282 00:13:58,360 --> 00:14:03,070 But we don't follow these titers sequentially like we do in 283 00:14:03,070 --> 00:14:04,450 lupus, for example, 284 00:14:04,450 --> 00:14:07,240 where we assess double stranded DNL complement levels 285 00:14:07,240 --> 00:14:08,530 that are more indicative 286 00:14:08,530 --> 00:14:11,950 of an improvement in disease activity or remission. 287 00:14:11,950 --> 00:14:14,530 So majority of the benefit 288 00:14:14,530 --> 00:14:17,200 of lab testing in scleroderma is largely 289 00:14:17,200 --> 00:14:18,460 diagnostic and prognostic. 290 00:14:19,300 --> 00:14:23,585 - Wow. So I 291 00:14:24,505 --> 00:14:27,580 I think one thing I'm curious about in this, you know, 292 00:14:27,580 --> 00:14:30,280 as you talk about these changes that can happen, 293 00:14:30,280 --> 00:14:31,660 and I think you're getting a little bit 294 00:14:31,660 --> 00:14:34,705 of adrenal discharge from me as you're talking about this 295 00:14:34,705 --> 00:14:36,490 'cause I have an appreciation for 296 00:14:36,490 --> 00:14:39,820 how the immune system sometimes can seem 297 00:14:39,820 --> 00:14:42,010 to turn on a dime, right? 298 00:14:42,010 --> 00:14:44,950 As as it's designed to do to to fight infection. 299 00:14:44,950 --> 00:14:48,400 The, like, can you give our audience listeners kind 300 00:14:48,400 --> 00:14:50,295 of a sense for, you know, 301 00:14:50,295 --> 00:14:54,410 how dynamic can this disease be when you talk about, 302 00:14:54,410 --> 00:14:59,410 you know, somebody can develop these changes with, you know, 303 00:14:59,420 --> 00:15:03,440 hypertension and, and have like medical consequences. 304 00:15:03,440 --> 00:15:05,185 'cause when I hear you say that 305 00:15:05,185 --> 00:15:06,955 and talk about pulmonary hypertension, right? 306 00:15:06,955 --> 00:15:10,100 Heart failure, that definitely gets my attention 307 00:15:10,100 --> 00:15:13,160 and something definitely we wanna mitigate. 308 00:15:13,160 --> 00:15:15,080 What, what are we talking about for how, 309 00:15:15,080 --> 00:15:16,820 how rapid does this come about? 310 00:15:16,820 --> 00:15:19,730 - Yes, yes. And that's a very important question. 311 00:15:19,730 --> 00:15:23,540 I think no two scleroderma patients are the same 312 00:15:23,540 --> 00:15:26,395 and no two scleroderma journeys are going 313 00:15:26,395 --> 00:15:28,220 to be the same long-term. 314 00:15:28,220 --> 00:15:29,270 And that, and that's a key point 315 00:15:29,270 --> 00:15:31,340 because there, there can be 316 00:15:35,360 --> 00:15:38,150 patients with very higher immune suppression 317 00:15:38,150 --> 00:15:40,010 through their entire disease course. 318 00:15:40,010 --> 00:15:41,570 Whereas the other patients 319 00:15:41,570 --> 00:15:45,170 with more diffused cutaneous phenotype in particular have a 320 00:15:45,170 --> 00:15:48,140 very rapid onset of lots 321 00:15:48,140 --> 00:15:51,320 of different internal organ manifestations within their 322 00:15:51,320 --> 00:15:53,450 first five years of disease. 323 00:15:53,450 --> 00:15:58,450 That is the timeframe during which we see the most rapid 324 00:15:58,460 --> 00:16:00,955 trajectory for internal organ disease, 325 00:16:00,955 --> 00:16:05,000 whether it be skin progression, joint inflammation, 326 00:16:05,000 --> 00:16:07,790 whether it be interstitial lung disease progression, 327 00:16:07,790 --> 00:16:09,140 and you know, 328 00:16:09,140 --> 00:16:12,800 other manifestations like myocarditis for example. 329 00:16:12,800 --> 00:16:15,565 But pulmonary hypertension on the other hand is a late 330 00:16:15,565 --> 00:16:18,830 manifestation and can often develop post five years 331 00:16:18,830 --> 00:16:20,330 to 10 years of disease. 332 00:16:20,330 --> 00:16:24,680 So some of those monitoring strategies need to continue 333 00:16:24,680 --> 00:16:28,220 beyond the five year mark, even though you might have dealt 334 00:16:28,220 --> 00:16:30,680 with a big storm initially. 335 00:16:30,680 --> 00:16:32,360 So first five years are very key 336 00:16:32,360 --> 00:16:35,150 to keep these patients under really close follow up. 337 00:16:35,150 --> 00:16:37,285 But subsequent to that as well, 338 00:16:37,285 --> 00:16:40,730 periodic monitoring under the care of a rheumatologist is 339 00:16:41,780 --> 00:16:43,670 very helpful in my opinion. 340 00:16:44,630 --> 00:16:47,360 - Well, I really appreciate like you sharing your expertise 341 00:16:47,360 --> 00:16:50,240 and helping all of our listeners really kind of follow on, 342 00:16:50,240 --> 00:16:54,350 get an appreciation for how dynamic 343 00:16:55,250 --> 00:16:57,290 this rare disease can be 344 00:16:57,290 --> 00:17:01,790 and how important it is that we are thinking about this 345 00:17:01,790 --> 00:17:03,890 and aware of this diagnosis. 346 00:17:03,890 --> 00:17:06,080 A couple of times through our conversation here, 347 00:17:06,080 --> 00:17:08,210 you've mentioned, you know, 348 00:17:08,210 --> 00:17:10,550 how this is evolving and, and changing. 349 00:17:10,550 --> 00:17:13,040 I'm kind of curious for your thoughts on 350 00:17:13,040 --> 00:17:15,740 what's on the horizon for folks 351 00:17:15,740 --> 00:17:17,510 that are diagnosed with scleroderma. 352 00:17:17,510 --> 00:17:19,220 I'm, I'm kind of keeping an eye 353 00:17:19,220 --> 00:17:22,760 for our student listeners right, who might be, you know, 354 00:17:22,760 --> 00:17:24,145 interested in research 355 00:17:24,145 --> 00:17:28,610 or may wanna be following in, in your footsteps to become a, 356 00:17:28,610 --> 00:17:32,300 a rheumatologist with this particular interest. 357 00:17:32,300 --> 00:17:33,710 How is the field evolving? 358 00:17:34,610 --> 00:17:37,040 - Yeah, the field is evolving really rapidly 359 00:17:37,040 --> 00:17:39,110 and I'm really excited about that 360 00:17:39,110 --> 00:17:41,065 because we have so much more 361 00:17:41,065 --> 00:17:44,990 to offer our patients than has existed ever before. 362 00:17:44,990 --> 00:17:46,100 Just in the last couple 363 00:17:46,100 --> 00:17:50,190 of years we've had two FDA approved medications, 364 00:17:50,190 --> 00:17:52,650 very different from immune suppressants. 365 00:17:52,650 --> 00:17:56,820 So one is an antifibrotic medication, which is called 366 00:17:56,820 --> 00:17:58,950 nintedanib, and 367 00:17:58,950 --> 00:18:03,950 that is a whole different pathway of intervention 368 00:18:03,960 --> 00:18:05,400 to preserve lung function. 369 00:18:05,400 --> 00:18:09,300 In particular in these patients term, there are number 370 00:18:09,300 --> 00:18:12,120 of new immune suppressants in the pipeline. 371 00:18:12,120 --> 00:18:15,000 We're able to offer long transplants, 372 00:18:15,000 --> 00:18:17,130 hematopoietic stem cell transplant. 373 00:18:17,130 --> 00:18:19,470 It's actually an approved indication 374 00:18:19,470 --> 00:18:24,330 for stem cell transplant now as well as CAR T cell therapy. 375 00:18:24,330 --> 00:18:26,700 That is one of the exciting areas 376 00:18:26,700 --> 00:18:31,110 of investigation currently, we've had some patients go into 377 00:18:31,110 --> 00:18:35,580 remission with deep B-cell depletion 378 00:18:35,580 --> 00:18:36,780 that is sustained 379 00:18:36,780 --> 00:18:41,555 and it is impressive the trajectory of these patients 380 00:18:41,555 --> 00:18:45,360 because we don't, we've never seen that sort of response 381 00:18:45,360 --> 00:18:47,850 with scleroderma patients, even though it's a handful. 382 00:18:47,850 --> 00:18:50,970 It might be single center studies at this point, 383 00:18:50,970 --> 00:18:54,420 but we're very excited to see how this pans out 384 00:18:54,420 --> 00:18:58,440 and extend the benefits of therapies like this 385 00:18:58,440 --> 00:19:01,260 to maybe a larger spectrum of the population. 386 00:19:01,260 --> 00:19:03,180 This is really a very horrible 387 00:19:03,180 --> 00:19:06,300 and challenging disease to manage when it's severe, 388 00:19:06,300 --> 00:19:10,740 and I think there's a lot of room for advancement there. 389 00:19:11,790 --> 00:19:14,670 - Wow. I I wanna say thank you for the shout out 390 00:19:14,670 --> 00:19:17,400 for those students who might be interested in pathology. 391 00:19:17,400 --> 00:19:21,660 As Dr. Makol said that we, you know, cellular therapy, 392 00:19:21,660 --> 00:19:22,980 regenerative medicine is, 393 00:19:22,980 --> 00:19:26,490 is playing a role in assisting in helping these patients. 394 00:19:26,490 --> 00:19:30,185 So if you're interested in pathology lab medicine, 395 00:19:30,185 --> 00:19:32,310 we have a home for you if you're interested in 396 00:19:32,310 --> 00:19:33,690 scleroderma as well. 397 00:19:34,620 --> 00:19:37,350 - There you go. - So thank you so much. 398 00:19:37,350 --> 00:19:38,910 We've been rounding with Dr. Makol. 399 00:19:38,910 --> 00:19:41,580 Thank you so much for, for talking about scleroderma 400 00:19:41,580 --> 00:19:45,210 and helping us celebrate this scleroderma awareness month. 401 00:19:46,260 --> 00:19:47,790 - Thank you for the kind invitation. 402 00:19:48,780 --> 00:19:50,520 - My pleasure. And to all of our listeners, thank you 403 00:19:50,520 --> 00:19:51,540 for joining us today. 404 00:19:51,540 --> 00:19:53,370 We invite you to share your thoughts 405 00:19:53,370 --> 00:19:54,780 and suggestions by email. 406 00:19:54,780 --> 00:19:59,700 Please direct any suggestions to MCL education@mayo.edu 407 00:19:59,700 --> 00:20:01,470 and reference this podcast. 408 00:20:01,470 --> 00:20:04,710 If you've enjoyed lab Medicine Rounds, please subscribe 409 00:20:04,710 --> 00:20:07,650 and until our next rounds together, we encourage you 410 00:20:07,650 --> 00:20:09,990 to continue to connect lab medicine 411 00:20:09,990 --> 00:20:13,290 and the clinical practice through insightful conversations.